Complex matrix for medico-biological application

FIELD: chemistry, medicine.

SUBSTANCE: complex matrix consists of at least one biologically compatible polymer of natural origin, structured with sewing agent, which represents two- or multi-functional molecule, selected from epoxides, epihalohydrines and divinyl sulphone, on said polymer inoculated are chains with molecular weight less than 50000 daltons, selected from polymers of natural origin of small size, preferably, derivatives of cellulose or other biological polymer derivatives which naturally are not present in human organism, and/or non-polymerised chains with properties of oxidation inhibitors or ability to inhibit reactions of matrix decomposition, preferably, vitamins, enzymes or molecules, consisting of one or several cycles, degree of inoculation, expressed as ratio of moles of inoculated molecules and quantity of moles of polymer units, constitutes from 10 to 40%. Also described are method of obtaining such matrix and its application for separation, replacement, filling or addition of biological fluid or tissues.

EFFECT: increase of application efficiency.

20 cl, 7 ex, 2 tbl, 1 dwg

 

The present invention relates to a complex matrix, which consists of at least one polymer of natural origin with greater functionality and allows you to replace fluids, separation of tissues or tissue augmentation. Proposed in the present invention, the matrix has a high persistence in vivo, which is provided by slowing down its chemical, biological and mechanical decomposition.

In the present invention, a method and compositions in the form of a comprehensive, fully biodegradable, but high survivability in vivo matrix, which consists of at least one polymer of natural origin, for medical (pharmacologically active) funds applicable to stimulate the separation of tissues or increase their viscosity.

To replace the natural synovial fluid, which is not able to provide security functions of cartilage, lubricate and absorb the shocks due to the decrease of molecular weight of its constituent glycosaminoglycans, suffering arthritis patients often inject viscoelastic solution. Such substances are rapidly eliminated from the synovial sinus.

The increase in tissue is required for medical and cosmetic purposes.

For therapeutic purposes, the required increase is to some fabrics, in order to ensure the exercise of their functions; this may relate to the vocal cords, esophagus, urinary sphincter and other muscles.

Patients resort to cosmetic surgery to get rid of wrinkles, camouflage scars, enhance the lips. However, in addition to the high cost of such operations, they have many drawbacks, because they are invasive and dangerous procedures. Widely used method of injection of substances that can increase tissue. For these purposes, the use of hypodermic needles, the advantage of which is the simplicity and accuracy of their application and noninvasive procedures.

Produced substances for injection are stable or biodegradable means.

Pressively resistant tools

There are two approaches to the use of pressively means: injection of silicone or suspension of solid particles in a vector solution.

Injection silicone widespread. However, taking into consideration the undesirable long-term consequences (nodules, sores on the skin), this method is increasingly refuse [Edgerton and others, "Indications for and pitfalls of soft tissue augmentation with liquid silicone". Plast.Reconstr.Surg, 58: 157-163 (1976)].

Injection of solid microparticles also can achieve a sustained increase in tissue.

In U.S. patent 5344452 described n the applicatio powdered solid substances, formed by small particles with a diameter of from 10 μm to 200 μm with a smooth surface, known industrially produced substances Artecoll® and Arteplast®, which consists of a suspension of microspheres of polymethacrylate in a solution of collagen.

In the European patent EP-A-1091775 proposed to use a solution of hydrogel fragments methacrylate in a solution of hyaluronate. Also apply silicone particles, ceramic powder, carbon or metals (U.S. patent 5451406, 5792478, patent application U.S. 2002-151466), fragments of polytetrafluoroethylene, glass or synthetic polymers (patent application U.S. 2002-025340) and balls of collagen, but the results are unsatisfactory with regard to adverse reactions and biological dissolution and migration of residual products. Thus, the particles have at least one of the following disadvantages: too large a diameter or irregular shape, due to which they are linked with each other, making it difficult injected using a fine needle, too fragile particles during injection destroyed, too small particles quickly broken down by macrophages and other components of the lymphatic system, introduced with the injection of the particles are able to move and not attached to the surrounding cells.

The resistance of these substances leads to serious problems: the danger of intensified macropha is s, migration of synthetic fragments are part of them, or the appearance of granulomas, which may require steroid injections or even their excision. In addition, when using substances of this kind it is impossible to make corrections, if needed.

Among degrade biological materials may be mentioned solutions of crosslinked collagen or hyaluronic acid.

Known developed Collagen Corporation product based collagen, crosslinked hyaluronic acid (U.S. patent 4582640). This substance enzymatic or biochemical cleaved by macrophages, is removed by the lymphatic system and, thus, is rapidly degraded. This requires repeated treatments.

In U.S. patent 5137875 describes the use of aqueous suspensions or solutions of collagen containing hyaluronic acid, but this substance is not able to be in the form of a solution in the long course of treatment.

In the European patent EP 0466300 prompted to enter the injection of viscoelastic gel in the form of a matrix, dispersed in the liquid phase, and both phases are formed by gilana, which represents an extract of crosslinked high molecular weight hyaluronate animal.

To extend the period of absorption of the given fractions and thus retention time developed esters of hyaluronic acid and the school is made derivatives of hyaluronic acid. Among these substances, applicable for cosmetic purposes, you can mention Restylane®, two-phase gel, formed by a fluid phase (unstitched hyaluronate) and longevity highly crosslinked phase. While intramolecular or intermolecular bonds of polysaccharides or of the esters of acidic polysaccharides used in many purposes, for example, to prevent postoperative growths (European patent EP 0850074, U.S. patent 4851521, European patent EP 0341745), these substances are not able to provide sustainable long-term effect because of the high level of enzymatic cleavage and the short period of existence of complex ester bonds, which, in contrast to simple ester bonds fall in the physiological environment (U.S. patent 4963666).

There is a trend of using high-molecular polymers with the aim of increasing resistance of the matrix, or the degree of structuring. However, significant increase in the structure significantly reduces the period of existence of matter, which requires extremely careful handling of such longevity highly crosslinked gels, because the remaining parts of the polymer that are not protected by structuring, become mechanically and chemically fragile and more vulnerable.

In addition, a significant increase in the degree of structuring can lead to the fact that the substances will be difficult to enter videoshere.

In the European U.S. patent EP 0749982 proposed graft copolymerization of oxidation inhibitor and matrix with a low of only.

Thus, it is clear that the existing materials do not provide the perfect solution and continues the search for new substances to increase tissue, separation of tissues or increase their viscosity with the aim of creating materials with a high degree of biocompatibility, easily applicable in clinical practice, this period of existence, when the substance decomposes after it eliminates the need for it, but enough to limit medical and surgical intervention.

Summary of the invention

Despite the fact that the task of the tissue increases, separation of tissues and increase their viscosity known for a long time and offered many solutions for use in therapeutic or cosmetic purposes, in the present invention, a method and compositions provide long-term effectiveness of medical remedies without side effects. Such compositions can also be used as vectors for substances having a pharmacological action.

The present invention is based on the principle of using a large number of segments in the polymer chains to slow chemical and fer entatives impact directly on the main chain of the polymer. Due to the inoculation of small molecules with structuring increase the density matrix and thereby increase the time required for its decomposition, while limiting her mobility caused by excessively high degree of structuring. The connection between the two types of functionality - structuring and graft copolymerization also allows you to facilitate the application of the matrix for injection using a matrix with the same number of occupied sections of the main chain of the polymer, but with a higher degree of structuring. High resistance of the composition can be enhanced, if the grafted molecules have the properties of oxidation inhibitors. The oxidation inhibitors can also be dispersed in the matrix. The slow decomposition of the matrix can also be achieved through the use of cellulose derivatives or of other polymers, which by nature are not present in the human body, in the absence of specific hydrolytic enzymes.

The term "part"used in the context of the present invention, means the whole point of the polymer chain, which may be affected; this can be the side functional groups such as hydroxyl or carboxyl group or chain, such as ether linkages.

Due to the high resistance of medical devices can be increased is by the intervals between medical interventions and thereby improves the patient's quality of life.

Another objective of the present invention is to provide such compositions containing one or more molecules having a therapeutic effect.

Detailed description of the invention

In the present invention proposed a biologically compatible integrated single-phase matrix with high resistance, which consists of at least one polymer of natural origin with greater functionality. Under high resistance means the period of existence in vivo exceeding the period of existence of a substance with similar functionality, but obtained by the method different from the method proposed in the present invention, most often one random structure.

The substance is applicable for increasing the viscosity or increase the tissue is at least one polymer with a molecular weight of more than 100,000 daltons selected from polysaccharides, such as hyaluronic acid, chondroitin sulfate, keratan, Kermanshah, heparin, heparansulfate, cellulose and its derivatives, xanthane and alginates, proteins or nucleic acids, with such a polymer is given broad functionality by grafting small chains and structuring, thereby creating a matrix. The term " matrix " refers to a three-dimensional structure, education is organised by the polymers of biological origin with functionality, doubled by structuring and vaccinations.

A crosslinking agent chosen, in particular, of the two - or multifunctional epoxides, for example 1,4-potentialapplications ether (also called 1,4-bis(2,3-epoxypropoxy)butane), 1-(2,3-epoxypropyl)of 2,3-epoxycyclohexane and 1,2-ethiological ether, epichlohydrin and diphenylsulfone.

The degree of structuring, expressed as the ratio of the number of moles of forming the structure of the substance which provides the crosslinking of polymer chains, and the number of moles of the structure of the polymer is from 0.5 to 25% in relation to the substances introduced in the form of injections, from 25 to 50% with respect to solids.

To increase the spatial size and increase the density matrix and thereby extend the time required for chemical or biochemical decomposition, a small chain grafted to the matrix by means of ionic or covalent bonds, preferably by the formation of ethers. Such grafted chains occupy a large number of sites on the matrix, which can significantly prolong the period of existence of matter without modifying the mechanical or rheological characteristics of the polymer constituting the matrix. Mechanical protection is added to the biological and chemical protection, which provide the "bait".

Chain grafted to function the optional hydroxyl group or carboxyl type, on the one hand, directly protect such unreacted functional groups, and, on the other hand, indirectly protect the rest of the areas detected by steric hindrance.

Grafted chains and polymers of natural origin of the small sizes are more accessible to the impact areas than the areas masked by the matrix, or polymers, is not recognized by the enzymes of the body. In the latter case, it is derivative of cellulose derivatives or of other biopolymers, which by nature are not present in the human body, is not subject to degradation by enzymes of the body, but sensitive to the effects of free and others with the reactivity of radicals. For example, such a derivative of cellulose may be carboxymethyl cellulose.

In addition, the grafted chains can be an unpolymerized chain with properties of oxidation inhibitors or the ability to slow down the decomposition reaction of the polymer matrix. These circuits may be formed, for example, vitamins, enzymes or cyclic molecules.

The degree of grafting, which is expressed as the ratio of the number of moles of the grafted molecules or the number of moles of the grafted polymer and the number of moles of the structure of cross-linked polymer or polymer is from 10 to 40%.

Due to vaccinations the chain is small, in other words, with a molecular mass of less than 50,000 daltons, preferably about 10,000 daltons or less, on many points of the polymer matrix of the final product retains the ability to be input in the form of injections, because the degree of structuring is not increased, and the presence of grafted chains prevents the influence of the environment on the matrix and provides a higher durability of the product after the injection.

Inoculation of molecules is carried out using covalent bonds directly to the main chain, for example, through the formation of ester or a simple ester of hydroxyl or carboxyl groups, or using two - or multi-functional molecules are selected from epoxides, epichlohydrin or diphenylsulfone.

Specialists in the art will easily understand that this type of functionality has important advantages compared to the simple structuring.

Inoculation and structuring can occur simultaneously or vaccination may precede the structuring or Vice versa.

To slow decomposition under the action of free radicals in the matrix with greater functionality also dispersed molecule with the properties of the oxidation inhibitor.

For example, to inhibit the oxidation of organic makr the molecules, trapping of free radicals, but also to stimulate the synthesis of extracellular matrix, especially collagen in nevospalennyh tissues, apply vitamin C, extra long water-soluble molecules which possess the properties of oxidation inhibitors. This property may be of particular interest when applied in dermatological or cosmetic purposes to improve skin elasticity.

Vitamin a, which has many advantages (anti-oxidant effect, influence on the development of tissues and involved in the treatment of skin), also dispersed in such undergone significant modification of the matrix, which due to its density provides the gradual release of the current pharmacological tools.

In the matrix also dispersed released in a very small amount of melatonin, which is a potent inhibitor of the oxidation and restore the skin and protect the immune system.

To slow down the enzymatic decomposition, the structure of the matrices proposed in the present invention, it is recommended to use polymers that are by nature not contained in the human body, such as derivatives of cellulose, in particular carboxymethylcellulose, in the absence of specific hydrolytic enzymes such polymers.

As a result of significant Wuxi is possible steric interaction, blocking a large number of susceptible to biological and chemical attack sites without giving the fragility of the other sections provide a high resistance proposed in the present invention substances due to vaccinations short circuits and a certain amount of cross-linking, which remains relatively small compared to other currently known substances.

In addition, due to such extend the functionality of multiple identical busy sections of the main chain of the polymer constituting the matrix, give the ability to be introduced in the form of injections unlike gels, modified only by the method of structuring.

The drawing shows a significantly delayed time decomposition of the input in the form of injections of substances proposed in the present invention, and the decomposition of two well-known substances Juvéderm® and Restylane® (composition based on the polysaccharide gel according to the U.S. patent 5827937).

The invention also relates to a complex matrix, which consists of at least one biocompatible crosslinked polymer of natural origin, in which the grafted chains with molecular weight of less than 50,000 daltons, with the degree of grafting of from 10 to 40%.

Biologically compatible polymer of natural origin, forming a matrix, preferably vybirayuthij polysaccharides, such as hyaluronic acid, chondroitin sulfate, keratan, Kermanshah, heparin, heparansulfate, cellulose and its derivatives, xanthane and alginates, proteins or nucleic acids.

In a preferred embodiment, the biologically compatible polymer of natural origin is a polymer, which by nature is not in the human body, such as a derivative of cellulose, xanthan gum or alginate, crosslinked, at least one polymer, which by nature is present in the human body selected from polysaccharides, such as hyaluronic acid, chondroitin sulfate, keratan, Kermanshah, heparin, heparansulfate, xanthane and alginates, proteins or nucleic acids.

Preferably the degree of structuring, expressed as the ratio of the number of moles of forming the structure of the substance which provides the crosslinking of polymer chains, and the number of moles of the structure of the polymer is from 0.5 to 50%, in particular from 0.5 to 25% in relation to the substances introduced in the form of injections, from 25 to 50% with respect to solids.

A crosslinking agent, providing structuring circuit is a two - or multi-functional molecule selected from epoxides, epichlohydrin and diphenylsulfone.

The matrix may contain oxidation inhibitors, vitamins, or on the other dispersed substances, having a pharmaceutical effect.

The invention also relates to the use of the above matrix to replace, fill, or additions of biological fluid or tissue.

The invention also relates to a method for obtaining a biologically compatible matrix which is partially biologically decomposable and consists of at least one polymer of natural origin, characterized in that exercise

- grafted copolymerization of a small chain with a molecular weight of less than 50,000 daltons, with a degree of grafting of from 10 to 40%,

- structuring the main chains of the polymer to create a homogeneous matrix.

Examples

The examples are intended to illustrate the invention but in no way to limit the scope of the invention.

The first group of examples (examples 1-3):

Example 1 (structuring)

150 mg of sodium hyaluronate (molecular weight = 2×106daltons) and 50 mg of carboxymethyl cellulose (molecular weight = 2×105daltons) was added to 6 ml of 0.5% ash. The mixture is homogenized in a mixer to obtain a clear solution. Then to the solution was added 10 l 1,4-potentialapplications ether (BDDE) and stirred the mixture for 12 hours at 20°C. the pH of the mixture was brought to a physiological level. Then, the resulting matrix within 24 hours all the RGALI to dialysis (regenerated cellulose, the allocation limit, molecular weight = 12,000-14,000) using a solution of phosphate buffer at pH=7 (gel 1).

Example 2 (structuring)

150 mg of sodium hyaluronate (molecular weight = 2×106daltons) and 50 mg of carboxymethyl cellulose (molecular weight = 2×105daltons) was added to 6 ml of 0.5% ash. The mixture is homogenized in a mixer to obtain a clear solution. Then to the solution was added 20 l 1,4-potentialapplications ether (BDDE) and stirred the mixture for 12 hours at 20°C. the pH of the mixture was brought to a physiological level. Then, the resulting matrix within 24 hours dialyzed (regenerated cellulose, the allocation limit, molecular weight = 12,000-14,000) using a solution of phosphate buffer at pH=7 (gel 2).

Example 3 (structuring and inoculation

150 mg of sodium hyaluronate (molecular weight = 2×106daltons) and 50 mg of carboxymethyl cellulose (molecular weight = 2×105daltons) was added to 6 ml of 0.5% ash. The mixture is homogenized in a mixer to obtain a clear solution. Then to the solution was added 20 l 1,4 - potentialapplications ether (BDDE) and stirred the mixture for 8 hours at 20°C. was Added 40 mg of benzylmalonate (75% converted into ester, molecular weight = 104daltons), and was stirred to use the e for 12 hours at 20°C. Then added 10 mg of vitamin C and injected in a viscous matrix. the pH of the mixture was brought to a physiological level. The mixture was stirred for 2 hours. Then, the resulting matrix within 24 hours dialyzed (regenerated cellulose, the allocation limit, molecular weight = 12,000-14,000) using a solution of phosphate buffer at pH=7 (gel 3).

The calculation of the degree of grafting:

The degree of grafting=((mwits/Mwits+(mHaensel/MHaensel))/((mHA/MHA)+

(mCMC/MCMC))=0.246 (i.e. 24,6%),

where m: mass in grams

M: molecular weight polymer units in g/mol

Vit C: vitamin C

HA: hyaluronate

Haensel: benzylmalonate

CMC: carboxymethylcellulose.

The degree of grafting, calculated on the basis that all carboxyl groups are present as salts of sodium, and the degree of substitution of carboxymethyl cellulose is 0.9, is 24,6%.

Rheological studies showed a slower decline of these properties of the gel from example 2 (gel 2)than the gel from example 1 (gel 1) at 37°C. Despite the absence to date, in vivo studies, the decomposition of the gel 2 probably is slower than gel 1, which itself must decompose slower than the gel synthesized in the same manner but containing only sodium hyaluronate. This assumption can is about to do based on the data relating to the period of the existence in vivo of unstructured carboxymethylcellulose compared to unstructured sodium hyaluronate in the same concentration and with comparable molecular weight.

The period of existence of gel 2 exceeds the lifetime of the gel from the first example due to a doubling in the degree of structuring.

The number of spots in the gel of example 3 (gel 3)at least equal to the number of such sites in the gel 2, and the decrease of the viscosity of the gel 3 is slower than the gel 2 (when both gel are at a temperature of 37°C).

The second group of examples (examples 4-7):

Example 4 (structuring)

1 g of sodium hyaluronate (molecular weight = 2×106daltons) was placed in 10 ml of 1% solution of soda. The mixture is homogenized in a mixer to obtain a clear solution. Then added 100 l 1,4-potentialapplications ether (BDDE) and again stirred the mixture for 2 hours at 50°C. the pH of the mixture was brought to a physiological level, and reduced the mixture to 50 ml by adding phosphate buffer. Then, the resulting matrix within 24 hours dialyzed (regenerated cellulose, the allocation limit, molecular weight = 12.000-14.000) using a solution of phosphate buffer at pH=7 (gel 4).

Example 5 (structuring)

1 g of sodium hyaluronate (Molek is lar mass = 2×10 6daltons) was placed in 10 ml of 1% solution of soda. The mixture is homogenized in a mixer to obtain a clear solution. Then added 130 l 1,4-potentialapplications ether (BDDE) and again stirred the mixture for 2 hours at 50°C. the pH of the mixture was brought to a physiological level, and reduced the mixture to 50 ml by adding phosphate buffer. Then, the resulting matrix within 24 hours dialyzed (regenerated cellulose, the allocation limit, molecular weight = 12,000-14,000) using a solution of phosphate buffer at pH=7 (gel 5).

Example 6 (structuring)

0.8 g of sodium hyaluronate (molecular weight = 2×106daltons) and 0.2 g of carboxymethyl cellulose (molecular weight = 3×105daltons) was placed in 10 ml of 1% solution of soda. The mixture is homogenized in a mixer to obtain a clear solution. Then added 130 l 1,4-potentialapplications ether (BDDE) and again stirred the mixture for 2 hours at 50°C. the pH of the mixture was brought to a physiological level, and reduced the mixture to 50 ml by adding phosphate buffer. Then, the resulting matrix within 24 hours dialyzed (regenerated cellulose, the allocation limit, molecular weight = 12,000-14,000) using a solution of phosphate buffer at pH=7 (gel 6).

Example 7 (structuring and inoculation

0.8 g of sodium hyaluronate (molecular weight = 2×10 6daltons) and 0.2 g of carboxymethyl cellulose (molecular weight = 3×105daltons) was placed in 10 ml of 1% solution of soda. The mixture is homogenized in a mixer to obtain a clear solution. Then added 130 l 1,4-potentialapplications ether (BDDE) and again stirred the mixture for 1 hour and 20 minutes at 50°C. Then the gel formation process added 0.2 g of heparin (molecular weight = 3×103daltons), dissolved in 4 ml of 0.5% solution of soda, and again mixed mixture. the pH of the mixture was brought to a physiological level, and reduced the mixture to 50 ml by adding phosphate buffer. Then, the resulting matrix within 24 hours dialyzed (regenerated cellulose, the allocation limit, molecular weight = 12,000-14,000) using a solution of phosphate buffer at pH=7 (gel 7).

The calculation of the degree of grafting:

The degree of grafting=(mheparin/Mheparin)/((mHA/MHA)+(mCMC/MCMC)=10,3%,

where m: mass in grams

M: molecular weight polymer units in g/mol

HA: hyaluronate

CMC: carboxymethylcellulose.

The degree of grafting was calculated from the calculation that half an ionisable groups is in the form of salts of sodium, and the degree of substitution of carboxymethyl cellulose is 0.9, is 10.3%.

In addition, we developed a method for quantitative evaluation of the use of the value in the form of injections of different gels, obtained in examples 1-7. This method is based on measuring the force required to eject a variety of the obtained gels through a needle type 27G. In the syringe, the end of which there was a needle type 27G, gaining 1 ml each of the resulting gel. The syringe is held vertically over the holder and then hit the plunger of the syringe force with a constant speed set by the user. The sensor measured the force required to push the matter. For gels from the first group of examples, the speed of ejection was 75 mm/min and gels from the second group of 15 mm/min

Below in tables 1 and 2 shows the amount of force measured for the gels of examples 1-7.

Table 1
GelsThe force of buoyancy. Speed = 75 mm/min
1 (structuring)20N+/-4H
2 (structuring)N+/-4H
3 (structuring and vaccination)25N+/-4H

As follows from the results given in the table at the same degree of structuring to eject crosslinked and grafted gels according to the present invention requires less stress is (and therefore, they are more applicable in the form of injections)than to propel the crosslinked gels (comparison of gels from example 2 and example 3).

Table 2
GelsThe force of buoyancy. Speed = 15 mm/min
4 (structuring)14N+/-4H
5 (structuring)23 N+/-4H
6 (structuring)N+/-4H
7 (structuring and vaccination)24N+/-4H

As follows from the Table, increasing the degree of structuring leads to an increase in the effort required to propel the substance (comparison of gels 4-6). At the same degree of structuring cross-linked gels on the basis of HA/CMC is less applicable in the form of injections. However, the greater applicability of the resistance of such gels should also be higher. The last example (comparison of gels 6 and 7) underlines the fact that the vaccine is small chains of heparin reduces the force required to eject, with simultaneous protection of the crosslinked matrix due to steric hindrances and biological properties of such a polymer.

1. Comprehensive the matrix, which consists of at least one biocompatible polymer of natural origin, structured cross-linking agent, representing two - or multi-functional molecule selected from epoxides, epichlohydrin and diphenylsulfone, called the grafted polymer chains with molecular weight of less than 50,000 Da, selected from polymers of natural origin are of small size, preferably, cellulose derivatives or other derivatives of biological polymers, which by nature are not present in the human body, and/or unpolymerized chains with properties oxidation inhibitors or the ability to slow down the decomposition reaction of the matrix, preferably, vitamins, enzymes or molecules, comprising of one or more cycles, the degree of grafting, expressed as the ratio of the number of moles of the grafted molecules and the number of moles of the units of the polymer is from 10 to 40%.

2. The matrix according to claim 1, in which the biocompatible polymer of natural origin selected from hyaluronic acid, chondroitin sulphate, keratan, keratomalacia, heparin, heparansulfate, cellulose and its derivatives, xantinol and alginates, proteins or nucleic acids.

3. The matrix according to claim 1, in which the biocompatible polymer of natural origin isone polymer, which by nature is not in the human body, such as a derivative of cellulose, xanthan gum or alginate, crosslinked, at least one polymer, by nature, are contained in the human body selected from hyaluronic acid, chondroitin sulphate, keratan, keratomalacia, heparin, heparan sulfate, xantinol and alginates, proteins or nucleic acids.

4. The matrix according to claim 1, in which the degree of structuring, expressed as the ratio of the number of moles of cross-linking agent, providing crosslinking of polymer chains, and the number of moles of the units of the polymer is from 0.5 to 50%, in particular from 0.5 to 25% in relation to the substances introduced in the form of injections, from 25 to 50% with respect to solids.

5. The matrix according to claim 1, containing oxidation inhibitors, vitamins and other dispersed substances with pharmacological effects.

6. The matrix according to claim 1, containing vitamins or other dispersed substances with pharmacological effects.

7. The use of a matrix according to claim 1 for the separation, replacement, filling or additions to biological fluids or tissues.

8. A method of obtaining a partially biologically decomposable biologically compatible matrix which comprises at least one polymer of natural origin, characterized in that exercise grafted copoly is anizatio small chains with molecular weight of less than 50,000 Da with a degree of grafting of from 10 to 40%, such chains are selected from polymers of natural origin are small in size, preferably, cellulose derivatives or derivatives of other biological polymers, which by nature are absent in humans and/or unpolymerized chains with properties oxidation inhibitors or the ability to slow down the decomposition reaction of the matrix, preferably, vitamins, enzymes or molecules consisting of one or more cycles, the structuring of the main chains of the polymer to create a homogeneous matrix with the aid of a crosslinking agent, representing two - or multi-functional molecule selected from epoxides, epichlohydrin and diphenylsulfone.

9. The matrix according to claim 2, in which the biocompatible polymer of natural origin is a polymer, which by nature is not in the human body, such as a derivative of cellulose, xanthan gum or alginate, crosslinked, at least one polymer, by nature, are contained in the human body selected from hyaluronic acid, chondroitin sulphate, keratan, keratomalacia, heparin, heparan sulfate, xantinol and alginates, proteins or nucleic acids.

10. The matrix according to claim 2, in which the degree of structuring, expressed as the ratio of the number of moles of a crosslinking agent, by providing the tion of the polymer chains, and the number of moles of the units of the polymer is from 0.5 to 50%, in particular from 0.5 to 25% in relation to the substances introduced in the form of injections, from 25 to 50% with respect to solids.

11. The matrix according to claim 3, in which the degree of structuring, expressed as the ratio of the number of moles of cross-linking agent, providing crosslinking of polymer chains, and the number of moles of the units of the polymer is from 0.5 to 50%, in particular from 0.5 to 25% in relation to the substances introduced in the form of injections, from 25 to 50% with respect to solids.

12. The matrix according to claim 2, containing oxidation inhibitors, vitamins and other dispersed substances with pharmacological effects.

13. The matrix according to claim 3, containing oxidation inhibitors, vitamins and other dispersed substances with pharmacological effects.

14. The matrix according to claim 4, containing oxidation inhibitors, vitamins and other dispersed substances with pharmacological effects.

15. The matrix according to claim 2, containing vitamins or other dispersed substances with pharmacological effects.

16. The matrix according to claim 3, containing vitamins or other dispersed substances with pharmacological effects.

17. The matrix according to claim 4, containing vitamins or other dispersed substances having a pharmacological action

18. The matrix according to claim 5, containing vitamins or other dispersed substances with pharmacological effects.

19. The use of a matrix according to claim 2 for the separation, replacement, filling or additions to biological fluids or tissues.

20. The use of a matrix according to claim 3 for the separation, replacement, filling or additions to biological fluids or tissues.



 

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SUBSTANCE: invention relates to preparing biologically active chitosan substances and their derivatives. Invention describes a modified chitosan substance showing pH-neutral reaction and plastic structure of chitosan particles as fractal chitosan particles of size of nanofractals from 1 nm, not less, and to 5000 nm, not above, or as cross-linked net-shaped polymer having multiple cavities of size from 1 nm, not less, to 50 nm, not above. Invention describes methods for their preparing. Invention provides high transdermal penetration of chitosan substance and enhanced capacity for administration of medicinal or biologically active substances into chitosan substance. Invention can be used in manufacturing cosmetic, curative-cosmetic, pharmacological preparations, biologically active food supplements and foodstuffs.

EFFECT: improved and valuable properties of chitosan substances.

14 cl, 4 tbl, 7 dwg, 9 ex

FIELD: agriculture.

SUBSTANCE: invention describes a chitosan-base composition reducing the content of nitrates in plant growing production. The composition comprises chitosan of molecular mass 20-150 kDa, organic acids - mixture of succinic, ascorbic and sorbic acids in the mass ratio = 2:1:1, respectively, activating agents of nitrate and nitrite reductases - iron nitrate, ammonium molybdate, indolyl acetic acid and ethylenediaminetetraacetic acid in the mass ratio = 20:5:1:1, respectively; or iron nitrate, ammonium molybdate, indolyl acetic acid and N,N-dicarboxymethylglutamic acid in the mass ratio = 20:5:1:1, respectively, and substances enhancing synthesis of chlorophyll - 2-oxoglutaric acid and L-glutamic acid in the mass ratio = 30:1, and a surface-active substance also in the following ratio of above indicated components, wt.-%: chitosan, 15-25; organic acids, 15-25; activators of nitrate and nitrite reductases, 25-30; enhancers of chlorophyll synthesis, 29-35, and surface-active substance, 1-3. The composition provides enhancing assimilation of inorganic nitrogen in plant and reduces the content of nitrates in plant growing productions.

EFFECT: valuable properties of composition.

5 tbl

FIELD: production of new materials.

SUBSTANCE: proposed nanocomposite can be used as component contributing to charges of consumer properties of materials made on its base. Nanocomposite includes fibrils of filler-chitin individualized to nanosizes with distance between fibrils from 709 to 20-22 nm and water-soluble polymeric matrix in interfibril space. Degree of filling of nanocomposite is 0.05-0.25% mass. Fibrils are arranged in parallel and they have cross size of 4 nm. Method of production of nanocomposite comes to the following: free-radical polymerization in water medium of at least one monomer of row of acrylic acid, salt of acrylic acid, acrylamide is carried out in presence of filler. Initiator is chosen from the row of water-soluble peroxides, hydroperoxides or their salts, potassium persulfate. Individualization to nanosizes of fibrils is done simultaneously with process of polymerization and/or with combination of said process with mechanical disintegrating action by disintegrating or pressing, or pressing with abrasion shift. Nanocomposite is obtained in form of film, being pervaporation membrane.

EFFECT: enlarged range of filling, ease of production.

22 cl, 1 tbl, 9 ex, 2 dwg

The invention relates to macroporous chitosan granules having a relatively large and uniform pore size of 30-150 μm inside and outside, which are distributed from the surface to the area of the nucleus, and the way they are received, which includes the following stages: adding dropwise chitosan solution, the aqueous chitosan solution, or a mixture thereof in the low-temperature organic solvent or liquid nitrogen; regulation of pore size using the method of phase separation due to temperature differences
The invention relates to chemical technology, particularly to a method for producing a gel or suspension of chitosan, and can be used in food, cosmetic, pharmaceutical and other industries

The invention relates to a technology for production of absorbent compositions for the manufacture of disposable products actions absorbent body fluids

FIELD: chemistry.

SUBSTANCE: present invention relates to the method of producing functionalised, linked or star block copolymer, used in rubber compositions, cross-linked with sulphur and with low hysteresis in the cross-linked state. Described is a method of producing the said copolymer, containing soot and with low hysteresis in the cross-linked state. At least one or the above mentioned blocks consists of a diene elastomer, distinct from polyisoprene, the molar content of branches of one or several conjugate dienes of which exceeds 15%. The method is distinguished by that it involves: (i) copolymerisation of one or several monomers, containing at least one conjugated diene, distinct from isoprene, using a catalyst system, containing a hydrocarbon solvent, halogenation or non-halogenated organo-metal compound A of a group IIIA metal, compound B of an alkali-earth metal and a polymer initiator C, containing C-Li bond, which is formed from non-functionalised mono-lithium containing polyisoprene, meant for forming the said or each polyisoprene block; the said one or several polyisoprene blocks have average molecular mass Mn1 from 2500 to 20000 g/mol, in effect that, one or several blocks, containing diene elastomer, distinct from polyisoprene, contains 70% or more 1,4-trans-branches and has average molecular mass Mn2 from 65000 to 350000 g/mol, and (ii) addition into the copolymerisation product of a functionalised, linking or star structure forming agent, containing one, two or at least three epoxy groups, respectively, for functionalising, linking or forming a star structure of the given block, consisting of diene elastomer, distinct from polyisoprene. Description is also given a functionalised, linked or star block-copolymer, cross-linkable or cross-linked rubber composition, containing the said functionalised, linked or star block-copolymer, and description is also given of a pneumatic tyre tread and a pneumatic tyre.

EFFECT: obtaining a block-copolymer, which is used in compositions for pneumatic tyre treads, and which reduces hysteresis of the given composition in cross-linked state.

40 cl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention refers to making a moulded product for handling clean-room materials, intermediate products or end products, such as a container, a tray and a tool. The moulded product is made of resin compound prepared by mixing in melt cycloolefine polymer (A) 100 weight fractions chosen from the group including bicyclo[2.2.1]-2-heptene and its derivatives, tricyclo [4,3,0,12,5]-3-decene and its derivatives, and tetracyclo[4,4,0,12,5,17,10]-3-dodecene and its derivatives of vitrification temperature within 60 to 200°C, and amorphous or low-crystalline elastic copolymer (B(b1)) 1 to 150 weight fractions. Copolymer (B(b1)) is polymerised from at least two monomers chosen from the group including ethylene and a-olefin with 3 to 20 carbon atoms and vitrification temperature 0°C or lower. The compound contains radical polymerisation initiator 0.001 to 1 weight fractions containing peroxide, and polyfunctional compound (D) 0 to 1 weight fractions. The compound (D) has at least two radical-polymerised functional groups chosen from the group including vinyl group, allylic group, acrylic group and methacrylic group in a molecule.

EFFECT: clean-room moulded product is characterised with good chemical stability, heat resistance and dimensional accuracy, it prevents volatile component release in the surrounding space, has good abrasion resistance and prevents particle formation.

19 cl, 1 tbl, 2 dwg, 12 ex

FIELD: chemistry.

SUBSTANCE: there is disclosed foam thermoplastic gel composition containing (a) block copolymer containing at least one polymer block A made of monovinyl aromatic compound, and at least one polymer block B made of conjugated diene; (b) liquid component chosen from the group including filling oils, plasticiser and solvents compatible with said block copolymer (a); (c) thermoplastic particles foam when heated containing gas extended when heated or condensed gas, and optionally (d) photoinitiator characterised that block copolymer (a) represents a block copolymer cross-linked when irradiated and contains monovinyl aromatic compound 7 to 35 wt % of total polymer with total apparent molecular weight 50 to 1500 kg/mol and vinyl content in block B 10 to 80 mole %, where blocks B are probably hydrogenated thus residual initial ethylene unsaturation is at least 25 %. There is also disclosed production process of said foam elastic thermoplastic gel composition (versions), as well as application of said foam elastic gel composition.

EFFECT: production of low-density oil gels of improved hear resistance.

13 cl, 6 tbl, 7 ex

FIELD: nanotechnologies.

SUBSTANCE: invention relates to nanocomposite eligible for producing pneumatic diaphragms like inner tire liner of cars, trucks etc. The proposed nanocomposite comprises elastomer and nanoclay. Elastomer contained in nanocomposite represents a random copolymer of isoolefine with C4 to C7 and styrene monomer or isoolefine with C4 to C6 and multi-olefine comprising functionalised monomer link represented by group (I) suspended to elastomer E, i.e. (I) The proposed nanocomposite is produced by engagement of nanoclay, elastomer representing a random copolymer of isoolefine with C4 to C7 and styrene monomer or isoolefine with C4 to C6, engrafting promoter representing Lewis acid and, at least, one functionalising compound representing anhydrides of unsaturated carboxylic acids containing 3 to 23 carbon atoms.

EFFECT: nanocomposites feature improved properties of pneumatic diaphragm, namely, lower oxygen permeability.

61 cl, 5 ex, 2 tbl

FIELD: nanotechnologies.

SUBSTANCE: invention relates to nanocomposite eligible for producing pneumatic diaphragms like inner tire liner of cars, trucks etc. The proposed nanocomposite comprises elastomer and nanoclay. The elastomer is selected from a certain group of rubbers and copolymers including functionalised monomer links that comprises functional groups suspended to elastomer E and selected from the following composition or The nanocomposite is produced by engagement of (a) elastomer selected from a certain group of rubbers and copolymers, (b) at least, one functionalising compound selected from or (c) at least, one initiator of free-radical polymerisation and (d) nanoclay.

EFFECT: nanocomposites feature improved properties of pneumatic diaphragm, namely, lower oxygen permeability.

48 cl, 21 ex, 2 tbl

FIELD: textile, paper.

SUBSTANCE: invention relates to papermaking technology, precisely to production of modified paper with higher gas-proof and heat-protective properties, and can be applied in constructions, aircraft and automobile constructions, shipbuilding. The method includes treatment of paper with the mixture of 5-7% aqueous solution of polyvinyl alcohol with 5-7% aqueous solution of chitosan at their ratio 1:1 within 10-15 minutes, thereafter treatment with 15-20% aqueous solution of methyl phosphate borate and drying.

EFFECT: prepared modified paper has increased gas-proof and heat-protective properties, and resistance to thermal-oxidative degradation.

1 tbl, 6 ex

FIELD: textile, paper.

SUBSTANCE: invention relates to production technology of synthetic paper, precisely to production of modified paper with higher gas-proof and heat-protective properties, and can be applied in constructions, aircraft and automobile constructions, shipbuilding. The compound contains 5-7% aqueous solution of polyvinyl alcohol, 15-20% aqueous solution of methyl phosphate borate and 5-7% aqueous solution of chitosan at the following ratio, pts. wt. polyvinyl alcohol - 5-7; chitosan - 5-7; methyl phosphate borate - 15-20; water - 275-266.

EFFECT: increase of gas-proof and heat-protective properties, and resistance to thermal-oxidative degradation of modified paper.

2 tbl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention concerns complex acrylic silicon rubber polymer, method of its obtainment and application. Complex acrylic silicon rubber polymer features nucleus-core-shell structure, where vinyl monomer and hydrophilic monomer are linked on a nucleus; complex acrylic silicon core has interpenetrating grid structure where silicon rubber particles are dispersed with acrylic rubber during linking, and is formed on nucleus in dispersion medium. Shell is obtained by graft polymerisation of C1-C4-alkylmetacrylate on complex acrylic silicon core with interpenetrating grid.

EFFECT: obtaining complex acrylic silicon rubber polymer with excellent impact strength, weather resistance and shine, which can be efficiently applied as impact strength modifier of vinylchloride resin.

14 cl, 4 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: said invention relates to rubber-reinforced vinylarene polymers. Rubber-reinforced vinylarene (co)polymers are described. They have strictly bimodal morpholgy and consist of 55-90 wt % of rigid polymer matrix and 10-45 wt % of rubber-like phase dispersed in the said rigid polymer matrix in the form of grafted and occluded particles. The said rubber particles consist of 60-99 wt % of capsular, or "coat-core" type, particles and 1-40 wt % of "salami"-type particles, percent ratios being specified for rubber particles weight only. Difference between Hildebrand solubility parameter of elastomer, which forms rubber-like "capsular" particles and Hildebrand solubility parameter of elastomer, which forms "salami"-type particles, is 0.5 or over, mean diameter of "coat-core" type particles is 0.10 to 0.30 mcm, and mean diameter of "salami"-type particles is 1 to 5 mcm. Also, continuous process for production of bulk and suspended rubber-reinforced vinylarene (co)polymers is described.

EFFECT: production of rubber-reinforced vinylarene polymers, which contain particles of strictly bimodal distribution, with improved mechanical properties.

15 cl, 4 dwg, 1 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to a method of obtaining a resin composition. Description is given of the method of obtaining a resin composition through mixture in a molten mass of 100 weight parts of cyclic olefin polymer (A), whose glass transition temperature ranges from 60 and 200°C, and 1-150 weight parts of elastic polymer (B), with glass transition temperature 0°C or lower. Part of the cyclic olefin polymer (A) is first mixed in a molten mass with elastic polymer (B) and 0.001-1 weight parts of radical polymerisation initiator (C). The remaining cyclic olefin polymer (A) is then added and mixed in the molten mass. The ratio of the quantity of cyclic olefin polymer (A), initially added, to the quantity of the same polymer added later (initially added/added later) ranges from 1:99 to 70:30. Cyclic olefin polymer (A) is divided into two parts and added separately twice, such that, the mixture with a cross-linked structure can be diluted with cyclic olefin polymer (A), without a cross-linked structure. As a result, increase in the viscosity of the molten resin composition can be prevented.

EFFECT: good abrasion resistance and good moulding properties of the molten mass.

15 cl, 1 tbl, 4 ex

The invention relates to the technology of the chemical industry, namely the creation of an adhesive composition, which can be used in the food industry, in particular, factories, beer & soft drinks for automatic sticker labels on hydrophobic glass surface
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