Composition for hard tissue repair

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine. What is described is a composition for hard tissue repair containing 5 to 98.95 weight portions of a monomer (A), 1 to 75 weight portions of (meth)acrylate polymer (B) and 0.05 to 20 weight portions of a polymerisation initiating composition (C) containing an organoboron compound (c1) providing the ingredients (A), (B) and (C) total makes 100 weight portions. What is described is a kit for the hard tissue repair.

EFFECT: composition generates little setting heat and can provide for manipulations for a long period of time.

18 cl, 2 dwg, 11 tbl

 

The technical field

This invention relates to a composition for the reconstruction of hard tissue.

Background of invention

As bone cement for fixation of hard tissues such as bone and cartilage with an artificial joint materials for bone filling, used in the treatment of osteoporosis, etc., materials for artificial bones, etc. previously explored various compositions for the reconstruction of hard tissue. For example, he studied composition containing polymethyl methacrylate, methyl methacrylate and benzoyl peroxide (polymerization initiator), the composition containing (meth)acrylate, an inorganic filler, such as calcium phosphate, and an organic peroxide, and so on (see, for example, patent literature 1).

However, such compositions produce a lot of heat during curing, and there is a high risk of damage to the damaged tissue.

Using the composition for repair of hard tissues such as bones, typically the components to form the composition is pre-mixed in a container, etc., and then the composition is applied to the surface of the damaged part, considering manufacturability, prevention of infection, and so on, But the status of the composition after mixing sometimes affects the workability during application of the composition.

As the acrylic adhesive, using the e initiators, containing organoboron compounds have low toxicity, are of low hazard and high adhesive strength, their active use in dental practice (see, for example, patent literature 2). However, for other medical applications, such as used in surgery, requires further usovershenstvovanija adhesion to soft tissue or wound dressings, it is necessary to further improve stability during operation or processability of the composition between the mixing components and applying the composition on the treated area.

References

Patent literature

Patent literature 1: Japan Patent Laid-Open Publication No. 224294/1996;

Patent literature 2: Japan Patent Laid-Open Publication No. 110913/1997

Brief description of the invention

Technical problem

The aim of the present invention to provide compositions for the reconstruction of hard tissue, which emits little heat during curing and exceptional adaptability.

Solution

To solve the above problems were investigated compositions for the reconstruction of hard tissue. The reconstruction of hard tissue take into account the adhesion between the solid fabrics and filling in solid tissues, adhesion between the solid fabrics and synthetic fabrics, such as titanium, ceramics energeia steel, the adhesion between the solid tissues and other tissues, such as soft tissue, etc. When such recoveries are not taken into account the adhesion between the tooth and the filling material (i.e. dental use).

In the result, the inventors of the present invention found that the above problems can be solved by using a composition comprising a certain number of monomer, (meth) acrylate polymer and a specific initiating polymerization komposiziya initiator of polymerization.

That is, the composition for recovery of the solid fabric of the present invention includes from 5 to 98,95 weight parts of monomer (A), from 1 to 75 parts by weight of (meth)acrylate polymer (b) and 0.05 to 20 parts by weight of initiating polymerization of the composition (C) containing an organoboron compound (C1), provided that the total amount of components (A), (b) and (C) is 100 weight parts.

The polymer (B) preferably is a mixture of polymers, which comprises polymer particles (b1) having srednevekovoi molecular weight of 30×104up to 60×104and the specific surface area of from 1.5 to 4.5 (m2/g), polymer particles (b2) having srednevekovoi molecular weight of from 5×104up to 20×104and the specific surface area of from 0.51 to 1.2 (m2/g), and polymer particles (b3) having srednevekovoi the Molek is popular weight from 5×10 4up to 20×104and the specific surface area of from 0.1 to 0.5 (m2/g), and contains polymer particles (b1) in an amount of from 0 to 98 wt%. and polymer particles (b2) and polymer particles (b3) in a total amount of not less than 2 wt%. with respect to the total weight of the polymer particles (b1), (b2) and (b3), provided that the total number of polymer particles (b1), (b2) and (b3) is 100 wt%.

Preferably, initiate polymerization of the composition (C) contains an aprotic solvent (C2), having a boiling point of from 30°C to 150°C, in the amount of 30-80 weight parts per 100 weight parts of boron compound (C1). It is also preferable that initiate polymerization of the composition (C) contains an aprotic solvent (C2'), having a boiling point of from 50°C to 120°C, in the amount of 5-40 weight parts and the alcohol (C3) having a boiling point of from 60°C to 180°C, in an amount of from 0.2 to 5 weight parts per 100 weight parts of boron compound (C1).

Composition for the reconstruction of hard tissue preferably has a viscosity of from 0.4 to 2000000 SP within 30 seconds after mixing of components (A), (b) and (C).

Composition for the reconstruction of hard tissue may further include, for example, the polymerization inhibitor (D), the absorber of ultraviolet light, plasticizer and softening agent.

In the preferred embodiment of the invention, the content of ing is the polymerization inhibitor (D) in the composition is in the range from 10 to 5000 ppm no relation to the monomer (A).

The polymerization inhibitor (D) preferably represents at least one substance selected from hydroquinone, dibutylamino, simple nanometrology ether of hydroquinone, 2,6-di-tert-butylphenol, 2,6-di-tert-butyl-p-cresol, catechin, pyragollole, benzoquinone, 2-hydroxybenzophenone, p-methoxyphenol, t-butylcatechol, butylhydroxyanisole, butylhydroxytoluene and t-butylhydroquinone.

Composition for the reconstruction of hard tissue may further include at least one substance selected from:

anti-infective agents, antibiotics, antibacterial additives, antiviral agents, analgesics, combination analgesics, means reducing appetite, deworming drugs, anti-arthritis means, anti-asthma drugs, anticonvulsants, antidepressants, antidiuretic funds, Antidiarrhoeal funds, antihistamines, anti-inflammatory drugs, drugs against migraine, antiemetics, anti-tumor drugs, anti-parkinsonism, antipruritic drugs, antipsychotic drugs, antipyretic drugs, antispasmodic funds, anticholinergics, sympathomimetic funds, cardiovascular drugs, antiarrhythmic drugs, antihypertensive drugs, diuretics, vasodilators, is rest, of immunosuppressants, muscle relaxants, parasympatholytics drugs, stimulants, sedatives, tranquilizers, cholinergic funds, chemotherapeutic drugs, radiopharmaceuticals, medium, inducing the growth of bone tissue, heparin neutralizers, procoagulants, hemostatic means, xanthine derivatives, hormones, natural proteins or proteins synthesized by genetic engineering methods, polysaccharides, glycoproteins, lipoproteins, oligonucleotides, antibodies, antigens, vasopressin, and analogues of vasopressin, epinephrine, selectin, promoting coagulation toxins, inhibitors of factor activation of plasminogen activators of platelets, synthetic peptides having hemostatic action, and perfumes, such as orange oil, grapefruit oil, lemon oil, lime oil, clove oil, Wintergreen oil, peppermint oil, rectified peppermint, banana distillate, cucumber distillate, honey distillate, rose water, menthol, anethole, alkylsalicylate, benzaldehyde, MSG, ethylvanillin, thymol and vanillin.

The cured product obtained from the composition for the reconstruction of hard tissue 24 hours after the preparation of compositions for the reconstruction of hard tissue has a thickness of not less than 0 μm, length not less than 25 mm and a width of not less than 2 mm, preferably has a flexible elastic modulus measured at a testing speed of 2 mm/min, not less than 100 MPa and the tensile strength measured at a testing speed of 1 mm/min, not less than 10 MPa. Set for vosstanovleniya solid fabric of the present invention has a section that is placed contained in the above composition for the regeneration of hard tissue components of the monomer (A), (meth)acrylate polymer (b) and containing organoboron compound initiates the polymerization of the composition (C), in the form of two or more separate groups in arbitrary combination.

Set for the reconstruction of hard tissue, preferably, is of such a construction, in which the monomer (A), the polymer (b) and initiate polymerization of the composition (C) each placed separately, and the first monomer (A) is mixed with initiate polymerization of the composition (C) containing an organoboron compound, and then mixed with the polymer (B).

When the reconstruction of hard tissue kit contains the polymerization inhibitor (D), the set has a section in which the components of the monomer (A), methacrylate polymer (B) initiating polymerization of the composition (C) containing an organoboron compound, and the polymerization inhibitor (D), contained in the above composition for recovery firm the tissue, placed in two or more separate sets in arbitrary combination.

The set containing the polymerization inhibitor, preferably has such a structure in which the monomer mixture (a) and the polymerization inhibitor (D), the polymer (b) and initiate polymerization of the composition (S) each independently placed separately, and the first monomer mixture (a) and the polymerization inhibitor (D) is mixed with initiate polymerization of the composition (C) containing an organoboron compound, and then mixed with the polymer (B).

The kit may include a device that is used for applying the composition to recover a solid fabric obtained by mixing components (A), (b) and (C) and if necessary additional components.

The device is, for example, swab, brush, fiber ball, cloth, sponge ball or a piece of sponge.

In the above kit may further contain an aqueous solution for pre-treatment, containing 1-15% by weight. citric acid and 1-5 wt%. iron chloride (III).

Advantages of the invention

Composition for recovery of the solid fabric of the present invention allocates a small amount of heat during curing and in addition possesses exceptional adaptability.

Brief Description of Drawings

Fig.1 is sobo is a schematic representation, showing an example of a method of obtaining a sample of the cured product used in the examples of the present invention.

Fig.2 is a schematic illustration showing an example of a method of obtaining a sample of the cured product used in the examples (compressive strength) of the present invention.

Description of embodiments of the invention

Composition for regeneration of hard tissues of the present invention contains the monomer (A). As the monomer (a) may be any monomer without specific restrictions, which can be polymerized by the action described below is used to initiate the polymerization of the composition (C). As the monomer (A) can be any monofunctional and polyfunctional monomer, depending on the purpose of use.

Examples of the monomers (A) include methacrylate, acrylates and other vinyl compounds.

Of these monomers, acrylates and methacrylate are preferred because of the relatively low irritation to the human body (acrylates and methacrylate sometimes hereinafter referred to as (meth) acrylates).

Of the monomers (A) from the point of view exceptional adhesion properties to the hard tissues are preferred monomers having the acid group.

Therefore, the preferred embodiment of the present invented the I is using a combination of (meth) acrylate (having an acid group) and monomer, having acidic group, such as the monomer (A).

Examples of the monofunctional (meth) acrylate (having an acid group include:

the alkyl (meth) acrylates such as methyl (meth) acrylate, ethyl (meth) acrylate, propyl (meth) acrylate, butyl (meth) acrylate, hexyl (meth) acrylate, 2-ethylhexyl (meth) acrylate, dodecyl (meth) acrylate, lauryl (meth) acrylate, cyclohexyl (meth) acrylate, benzyl (meth) acrylate and isobornyl (meth) acrylate;

complex hydroxyanisole esters of (meth) acrylic acid such as 2-hydroxyethyl (meth) acrylate, 2-hydroxypropyl (meth) acrylate, 3-hydroxypropyl (meth) acrylate, 4-hydroxybutyl (meth) acrylate, 5-hydroxyphenyl (meth) acrylate, 6 hydroxyhexyl (meth) acrylate, 1,2-dihydroxypropyl mono (meth) acrylate, 1,3-dihydroxypropyl mono (meth) acrylate and erythritol mono (meth) acrylate;

polyalkyleneglycol mono (meth) acrylates such as diethylene glycol mono (meth) acrylate, triethylene glycol mono (meth) acrylate, polyethylene glycol mono (meth) acrylate and polypropyleneglycol mono (meth) acrylate;

monoalkyl ethers of (poly)allenglish (meth) acrylates, such as onomatology ether glycol (meth) acrylate, monotropy ether glycol (meth) acrylate, onomatology ether of diethylene glycol (meth) acrylate, onomatology ether of triethylene glycol (meth) acrylate, onomatology ether glycol (meth) acrylate and monoalkyl ether polypropyleneglycol (meth) acrylate;

complex peralkaline esters of (meth) acrylic acid, such as perforater (meth) acrylate and hexaferrites (meth) acrylate;

compounds of silane having a (meth) aryloxyalkyl group, such as γ - (meth) acrylonitrilebutadiene and γ - (meth) Acrylonitrile(trimethylsiloxy)silane; and

(meth) acrylates having a heterocyclic nucleus, such as tetrahydrofurfuryl (meth) acrylate.

Examples of the polyfunctional (meth) acrylate (having an acid group include:

poly (meth) acrylates of alcantarillas, such as ethylene glycol di (meth) acrylate, propylene glycol (meth) acrylate, butyleneglycol di (meth) acrylate, neopentylglycol di (meth) acrylate, hexyleneglycol di (meth) acrylate, trimethylolpropane three (meth) acrylate and pentaerythritol Tetra (meth) acrylate;

poly (meth) acrylates of polyoxyalkylene, such as diethylene glycol di (meth) acrylate, triethylene glycol di (meth) acrylate, polyethylene glycol di (meth) acrylate, dipropyleneglycol di (meth) acrylate, polypropyleneglycol di (meth) acrylate, dibutylamino di (meth) acrylate and dipentaerythritol hexa (meth) acrylate;

alicyclic or aromatic di (meth) acrylates represented by the following formula (I):

where R represents a hydrogen atom or a metal group, m and n is from 0 to 10, which may be the same or different is, and R' is any one of the following:

,,,,,,,,,,,;

alicyclic or aromatic epoxy (meth) acrylates represented by the following formula (2):

where R is a hydrogen atom or a metal group, n is from 0 to 10, and R1- any one of the following:

,,,,,,,,,,,;

and

polyfunctional (meth)acrylate having in the molecule of the urethane bond represented by the following formula (3):

where R is a hydrogen atom or grave group, and R2- any one of the following:

,,,, ,,,

Of these (meth) acrylates are preferred monofunctional (meth) acrylates include:

the alkyl (meth) acrylates such as methyl (meth) acrylate and ethyl (meth) acrylate;

hydroxyalkyl esters of (meth) acrylic acid such as 2-hydroxyethyl (meth) acrylate, 1,3-dihydroxypropyl mono (meth) acrylate and erythritol mono (meth) acrylate; and

polyethylene glycol mono (meth) acrylates, such as onomatology ether of triethylene glycol (meth)acrylate, triethylene glycol mono (meth)acrylate.

Preferred polyfunctional (meth) acrylates include:

di (meth)Crilly having in a molecule etilenglikolevye chain, such as triethylene glycol di (meth) acrylate and polyethylene glycol di (meth) acrylate;

compounds represented by the following formula (1):

where R is a hydrogen atom or a metal group, and m and n is from 0 to 10, which may be the same or different;

compounds represented by the following formula (2):

where R is a hydrogen atom or a metal group;

and compounds represented by the following formula (3):

where R is a hydrogen atom or a metal band. This (meth) acrylates can be used singly or in combination of two or more types.

Examples of mono is', having the acid group include:

monomers having a carboxylic acid group or its anhydrous group, such as (meth) acrylic acid and its anhydride,

1,4-di (meth) acrylonitrilebutadiene acid,

6-(meth) Acrylonitrile-1,2,6-tricarboxylic acid,

N-(meth) acryloyl-p-aminobenzoic acid,

N-(meth) acryloyl-o-aminobenzoic acid,

N-(meth) acryloyl-m-aminobenzoic acid,

N-(meth) acryloyl-5-aminosalicylic acid,

N-(meth) acryloyl-4-aminosalicylic acid,

4-(meth) aryloxyethylhalides acid and its anhydride,

4-(meth) aryloxypropanolamine acid and its anhydride,

4-(meth) ariloxipicolinamidei acid and its anhydride,

4-(meth) acrylamidoglycolate acid and its anhydride,

2-(meth) acryloyloxy acid,

3-(meth) acryloyloxy acid,

4-(meth) acryloyloxy acid,

β-(meth) acryloyloxy hydrosylate,

β-(meth) acryloyloxy gidromolot,

β-(meth) acryloyloxy hereafter,

11-(meth) acryloyloxy-1,1-undecadienal acid and

R-vinylbenzoic acid;

the monomers having the group of phosphoric acid, such as (2-(meth) aryloxides) phosphoric acid, (2-(meth) arylacetylenes) phosphoric acid and

10-(meth) acalokitesvara acid; and

the monomers having sulfonylurea group, such as p-styrelseledamot acid and 2-acrylamide-2-methylpropanesulfonic acid.

Of these monomers having an acid group, 4-methacryloxypropyltrimethoxy acid and its anhydride are preferred.

These monomers having the acid group may be used singly or in combination of two or more types. Having an acid group, monomers can be used in the form of calcium salts. When using these with the acid group of the monomer composition of the recovery of the solid fabric of the present invention have tencency to have improved adhesive properties.

Preferably having an acid group monomer is contained in an amount of 1-20 weight parts, more preferably 1-10 weight parts, even more preferably 1-8 weight parts, per 100 weight parts of the total amount of (meth) acrylate and a monomer having an acid group contained in the composition for recovery of the solid fabric of the present invention. If this amount is outside the above range, is shown an adverse effect on the adhesive strength with solid fabrics or biocompatibility with the body.

The amount of monomer (A) is preferably in the range from 5 to 98,95 weight parts, more preferably from 17 to 98.5 weight parts, even more preferred is sustained fashion from 24 to 86 weight parts, 100 weight parts of total monomer (A), the below-described polymer (b) and described below is used to initiate the polymerization of the composition (S).

If the amount of monomer (A) is less than the lower limit of the above range, increases the viscosity and difficulties arise in the application or by injection into the bone tissue and thus deteriorate the performance properties. If the amount of monomer (A) exceeds the upper limit of the above range, the adhesion strength and other properties, such as a flexible elastic modulus, tensile strength, compressive strength and Flexural strength, tend to deteriorate.

In the composition for recovery of the solid fabric of the present invention may further contain at least one polymer (C) selected from acrylate polymers and methacrylate polymers, methacrylate polymers, and acrylate polymers are hereinafter sometimes referred to as "(meth)acrylate polymers".

Examples of the (meth)acrylate polymers include:

unstitched polymers, such as polymethyl (meth) acrylate, polyethylene (meth) acrylate, methyl (meth) acrylate/ethyl(meth) acrylate copolymer, methyl (meth) acrylate/butyl (meth) acrylate copolymer and a copolymer of methyl (meth) acrylate/styrene; and

crosslinked polymers such as a copolymer of methyl (meth) acrylate/ethylene glycol di (meth) acrylate, the copolymer is ethyl (meth) acrylate/triethylene glycol di (meth) acrylate and a copolymer of methyl (meth) acrylia and butadiene monomer and polymers, which contain the partial calcium salt.

In the (meth)acrylate polymers also include organic or inorganic components, in which the oxides or salts of metals covered above unstitched or crosslinked polymers.

Srednevekovoi molecular weight of the polymer preferably is in the range from 1000 to 1000000, more preferably from 50,000 to 5000000, more preferably from 100000 to 500000. The glass transition temperature (Tg) of the elastomer is usually not higher than 20°C., preferably not higher than 0°C. the Above-mentioned molecular weight is a molecular weight in terms of standard polymethyl methacrylate, as determined by gel permeation chromatography (GPC).

The polymer (B) may consist of polymer particles. When the polymer (A) composed of polymer particles, they can be polymeric particles of many kinds.

Examples of such polymer particles include polymer particles (b1) having srednevekovoi molecular weight of 30×104up to 60×104and a specific surface area of from 1.5 to 4.5 (m2/g), polymer particles (b2) having srednevekovoi molecular weight of from 5×104up to 20×104and a specific surface area of from 0.51 to 1.2 (m2/g), and polymer particles (b3) having srednevekovoi molecular weight of from 5×104up to 20×104and a specific surface area of from 0.1 to 0.5 (m2/g).

Specific power is the ability of the polymer particles (b1) is, preferably, in the range from 1.5 to 4.5 (m2/g), more preferably from 2.0 to 4.0 (m2/g).

The specific surface of the polymer particles (b2) is preferably in the range from 0.51 to 1.2 (m2/g), more preferably from 0.6 to 1.0 (m2/g).

The specific surface of the polymer particles (b3) is preferably in the range from 0.1 to 0.5 (m2/g), more preferably from 0.2 to 0.45 (m2/g).

Volumetric average diameter of the polymer particles (b1) is usually in the range from 1 to 50 (μm), preferably, 1-40 (μm). Volumetric average diameter of the polymer particles (b2) is usually in the range from 0.1 to 40 (μm), preferably, 1-20 (μm). Volumetric average diameter of the polymer particles (b3) is usually in the range from 1 to 50 (μm), preferably 5-40 (μm). When the polymer (B) is a polymer mixture consisting of polymer particles (b2) and polymer particles (b3), and, if necessary, the polymer particles (b1), the total number of polymer particles (b2) and polymer particles (b3) preferably is not less than 2 wt%, more preferably not less than 5% weight. with respect to the total weight of the polymer particles (b1), polymer particles (b2) and polymer particles (b3). Sometimes the polymer mixture consists of polymer particles (b2) and polymer particles (b3) in the total amount 100% weight.

When the total number of polymer clay is different particles (b2) and polymer particles (b3) is not less than the lower limit of the above range, the polymer (C) may be homogeneous dispersed in the monomer (a) and well soluble in the monomer (A). Further, during the operation of filling the bone described composition as bone cement or during the process of adhesion between the bone tissue between the bone tissue and artificial materials such as titanium and ceramics, or adhesion between the bone tissue and other tissues, such as soft tissue, can also be inhibited rapid increase in viscosity which results in a sufficient duration. In addition, when the composition for recovery of the solid fabric of the present invention add the following describes the radiopaque environment during mixing does not occur deposition radiopaque medium, and x-ray contrast medium can be uniformly dispersed. When the polymer particles are polymer particles (b1), the total amount of the polymer particles (b2) and polymer particles (b3) is preferably not more than 99 wt%, more preferably not more than 95 wt%, even more preferably not more than 90 wt%. with respect to the total weight of the polymer particles (b1), polymer particles (b2) and polymer particles (b3). When the polymer particles are polymer particles (b1), the content of the polymer particles (b1), preferred is entrusted, is not more than 98 wt%, more preferably not more than 95 wt%. the total weight of the polymer particles (b1), polymer particles (b2) and polymer particles (b3). The content of the polymer particles (b1) is preferably at least 1 wt%, more preferably at least 5 wt%, even more preferably at least 10 wt%. the total weight of the polymer particles (b1), polymer particles (b2) and polymer particles (b3). When the polymer particles are polymer particles (b1) in the above amount, the deposition of a contrast medium is rarely the case, even if the composition of this invention contains a contrast medium.

The number of (meth)acrylate polymer (b) is preferably from 1 to 75 weight parts, more preferably 1-73 weight parts, even more preferably 15-73 weight parts per 100 weight parts of total monomer (A), (meth)acrylate polymer (b) and described below is used to initiate the polymerization of the composition (C). If the number of (meth)acrylate polymer (b) is less than the lower limit of the above range, the polymerization process becomes difficult, adhesion strength and other properties, such as a flexible elastic modulus, tensile strength, compressive strength, Flexural strength, deteriorate. If the number of (meth)acrylate polymer (B) exceeds the upper paragraph is published by third parties of the above-mentioned range, increases viscosity and difficult to use for bone tissue due to the decrease in processability. When the polymer (B) is a (meth) acrylate polymer is a mixture of polymer particles (b1), (b2) and (b3), the preferred options are the following embodiment of the invention, provided that the total amount of the polymer particles (b1), (b2) and (b3) is 100 wt%. and the total number of polymer particles (b2) and (b3) is at least 2 wt%, preferably, at least 5% weight. When the amount of the polymer (b) is not less than 35 weight parts, but less than 65 weight parts, per 100 weight parts of the total amount of the monomer (A), polymer (b) and initiate polymerization of the composition (C), the number of polymer particles (b1) is preferably in the range from 10 wt%. up to 98 wt%, more preferably from 20 wt%. to 95 wt%, the number of polymer particles (b2) is preferably not more than 90 wt%, more preferably not more than 80 wt%, and the number of polymer particles (b3) is preferably not more than 90 wt%, more preferably not more than 80 wt%.

Composition for recovery of the solid fabric of the present invention is characterized by using the below described boron compound (C1) as containing the initiator composition (C) and when the boron compound is added to the containing monomer compositions is AI, at a relatively early stage slowly begins and continues the polymerization reaction. This contrasts with the case of using a peroxide as an initiator of polymerization, which requires a relatively long time to start polymerization even when adding a polymerization initiator, and if the polymerization reaction once it starts, the reaction proceeds quickly and ends in a relatively short period of time. To prepare the composition, which preferably is used to restore the hard tissues and so on, it is important to use such a polymer (B) of the present invention in such amount, as described above with respect to the monomer (A). When using such a polymer (C) can not only ensure suitability for subsequent use in a long time, but also to provide a liquid state and consumer properties, which is preferable when used for the reconstruction of hard tissue, etc.

Contained in the composition for repair of hard tissues of the present invention initiate polymerization of the composition (C) contains as a main component boron compound (C1) and may contain, if necessary, aprotic solvent (C2) and alcohol (C3). Boron compound (C1) has such a t the tion, in the case of the presence of small amounts of oxygen or water, the rate of polymerization increases, and, as in the composition of the present invention is present containing a boron compound (C1) initiate polymerization of the composition (C), upon contact of the composition containing moisture body part of the composition penetrates into the solid tissue and begins initiating polymerization on the surface as the seeding operation solid tissue, and when applied to her. Thus, leakage of the composition and the monomer (A) is negligible. In addition, even after curing in the body of the composition, the remainder of the monomer (A) tends to be smaller in comparison with the composition using a peroxide as an initiator of polymerization. Accordingly, the composition of the present invention is more favorable for the organism.

Examples of the organoboron compounds (C1) include dealkiller, alkoxyalkyl, dealkiller and partially oxidized dealkiller.

Examples trialkylborane include trialkyls having alkyl group of 2-8 carbon atoms, such as criativo, tripropyl, triisopropyl, tribution, three-second-Bolivar, triisobutylene, repentive, trihexalon, trileptalbuy, triactive, tricyclopentadiene and tricyclohexyl. Alkyl group which may be any alkyl group with a straight chain, branched alkyl group and cycloalkyl group and contained in trialkylborane three alkyl groups may be the same or different.

Alkoxyalkyl represents, for example, monoatomically boron or dilaksanakan. More specifically, alkoxyalkyl, for example, is monoalkylation, such as butoxyethanol. Alkyl group alkoxyalkyl may be the same or different from the alkyl part of the alkoxy group.

Examples dialkylamino include dicyclohexylmethane, vitaminbody. Two alkyl groups of dialkylamino may be the same or different. Two contained in dialkylamino alkyl groups may be associated with the formation of the monocyclic or bicyclic structure. Examples of such compounds include 9-borabicyclo [3.3.1] nonan.

Partially oxidized dealkiller is a partially oxidized product of the above-mentioned trialkylborane. As partially oxidized trialkylborane preferred is partially oxidized tribution. As partially oxidized trialkylborane can be used partially oxidized dealkiller obtained by the addition of oxygen in quantities of, preferably, from 0.3 to 0.9 mol., more preferably 0.4 to 0.6 mol. on 1 mol. dealkiller.

From the above brigance is of such compounds are preferred tributive or partially oxidized tribution, more preferred is partially oxidized tribution. When used as the boron compound (C1) tributive or partially oxidized tributive improve not only the performance properties of the composition, but the composition has a suitable reactivity to moisture-containing organisms. When used as the boron compound (C1) tributive or partially oxidized tributive reaction begins and continues even in high moisture content, such as the body, so that the monomer rarely remains on the boundary surface between acheiva and body. Therefore, decrease harmful to the body characteristics. Such boron compound (C1) can be used separately or in combination of two or more types.

In initiating the polymerization of the composition (C) may contain aprotic solvent (C2). So as to initiate polymerization of the composition (C) contains an aprotic solvent organoboron compound is diluted and exothermic properties of volatile boron compound (C1) weaken and, therefore, work with the composition during transport, storage and mixing easier. When you use an extremely large number of songs from this is retene, fast heat can ingibirovaniya by reducing the exothermic properties, and therefore, damage to the body, which is in contact with the composition of the present invention tends to decrease. Boiling point aprotic solvent (C2) at 1 ATM is typically in the range from 30°C to 150°C, preferably 50°C. To 120°C. If the boiling point is lower than the lower limit of the above range, aprotic solvent evaporates or volatilizes from initiating polymerization of the composition during transport or during storage, and the effect of suppressing ignition of organoboron compounds (C1) tends to decline.

If the boiling point exceeds the upper limit of the above range increases the balance of an aprotic solvent in the cured product formed from the composition for the reconstruction of hard tissue, decreases the adhesion strength of the cured product from the processed part and other properties, such as a flexible elastic modulus, tensile strength, compressive strength and Flexural strength.

As the aprotic solvent (C2) is the preferred solvent, which is not containing an active hydrogen group which can react with the boron compound (C1), such as hydroxyl the group or mercaptopropyl, and capable of forming a homogeneous solution of a boron compound (C1). Examples of aprotic solvents (C2) include:

hydrocarbons, such as pentane, hexane, cyclohexane, heptane, benzene and toluene;

galoidovodorodami, such as torbenson, 1,1-dichloroethane, 1,2-dichloroethane and the so-called felony;

ethers, such as diethyl ether, diisopropyl ether, dimethyl ether of ethylene glycol, and tetrahydrofuran;

ketones, such as acetone, methyl ethyl ketone and diethylketone; and esters such as methyl acetate, ethyl acetate and isopropylacetate.

Of them, preferred are saturated aliphatic hydrocarbons such as pentane, hexane and heptane, ethers, and esters, preferred are hexane, diisopropyl ether and ethyl acetate.

These aprotic solvents (C2) can be used separately or in combination of two or more types.

The content of the aprotic solvent (C2) to initiate polymerization of the composition (C) is preferably 30 to 80 weight parts per 100 weight parts of boron compound (C1).

If the content of the aprotic solvent (C2) is less than the lower limit of the above range is not achieved satisfactory effect of dilution and the effect of suppressing the heat generation or ignition is insufficient cnym. On the other hand, if the content of the aprotic solvent (C2) exceeds the upper limit of the above range, the ability to initiate polymerization of the composition (C) to initiate the polymerization becomes lower than necessary.

In initiating the polymerization of the composition (C) in addition to the aprotic solvent (C2) can optionally contain alcohol (C3). Adding to initiate polymerization of the composition (C) a small amount of alcohol (C3) can further weaken the jet action of the boron compound (C1) without reducing initiate polymerization activity, and even if the composition is brought into contact with paper, etc., on the air, inhibited the effect of fire or ignition.

The boiling point of the alcohol (C3) at 1 ATM is typically in the range from 60°C to 180°C, preferably from 60°to 120°C. If the boiling point is lower than the lower limit of the above range, the alcohol evaporates or volatilizes from initiating polymerization of the composition during transport or during storage, and the effect of suppressing ignition of organoboron compounds (C1) tends to decrease. If the boiling point exceeds the upper limit of the above range, increases the cure time of the composition of the present invention, decreases the adhesion strength Tveritinov the product with the processed part and other properties, such as a flexible elastic modulus, tensile strength, compressive strength and Flexural strength.

Examples of alcohols (C3) include methanol, ethanol, n-propanol and its isomers, n-butanol and its isomers, n-pengana and its isomers, n-hexanol and its isomers and n-heptanol its isomers.

Of these alcohols (C3) are preferred alcohols with 4 or less carbon atoms, namely methanol, ethanol, n-propanol and its isomers and n-butanol and its isomers, more preferred are ethyl alcohol and n-propanol.

These alcohols (C3) can be used separately or in combination of two or more kinds.

Alcohol content (C3) to initiate polymerization of the composition (C) is preferably in the range of from 0.2 to 5 weight parts, more preferably from 03 to 4.5 weight parts, even more preferably from 0.5 to 4 weight parts per 100 weight parts of organoboron compounds (b1).

If the content of alcohol (C3) is less than the lower limit of the above range, there is provided a satisfactory dilution effect and the effect of suppressing the heat generation or ignition is insufficient. On the other hand, if the content of alcohol (C3) exceeds the upper limit of the above range, initiating reduced ability to initiate polymerization of the composition (S).

When sleep is t (C3) and aprotic solvent (C2) are used in combination, the content of the aprotic solvent (C2) initiating polymerization of the composition (C) is preferably in the range of 5-40 weight parts, more preferably 10-30 weight parts, more preferably 10 to 25 weight parts, per 100 weight parts of boron compound (C1).

If the content of the aprotic solvent (C2) is less than the lower limit of the above range on 100 parts by weight of boron compound (C1), the effect of suppressing the generation of heat or ignition is insufficient. On the other hand, if the content of the aprotic solvent (C2) exceeds the upper limit of the above range on 100 weight parts of the boron compound (C1), initiating reduced ability to initiate polymerization of the composition (S).

The number of initiating polymerization of the composition (C) is preferably in the range of from 0.05 to 20 weight parts, more preferably 0.5 to 10 weight parts, more preferably 1-3 weight parts per 100 weight parts of total monomer (A), polymer (b) and initiate polymerization of the composition (S).

If the number of initiating polymerization of the composition (C) is less than the lower limit of the above range, the difficult process of polymerization and increases the cure time. If the number of the originating p is linerization composition (C) exceeds the upper limit of the above range, because of the dilution reduces the viscosity or there is a possibility of a negative impact on safety. In addition, with the rapid polymerization immediately formed the cured product.

In the composition for the reconstruction of hard tissue, if necessary, may further contain other components, as they do not render harmful influence on the operating characteristics of the composition.

As one of such other components may be specified polymerization inhibitor (D). Examples of polymerization inhibitors (D) include compounds hydroquinone, such as hydroquinone and dibutylamine, onomatology ether of hydroquinone, phenol, such as 2,6-di-tert-butylphenol and 2,6-di-tert-butyl-p-cresol, catechin, pyragollole, benzoquinone, 2-hydroxybenzophenone, p-methoxyphenol, t-butylcatechol, butylhydroxyanisole that is equivalent and t-butylhydroquinone.

Of these, the mixture nanometrology ether of hydroquinone and 2,6-di-tert-butyl-p-cresol is preferred.

Of these polymerization inhibitors (D) sometimes are preferred monomethylamine ethers of hydroquinone from the point of view of their good stability.

The above-mentioned polymerization inhibitors (D) can be used individually or in combination of two or more types.

When you add a polymerization inhibitor (D), its number is the primary objective is, preferably, in the range of 10-5000 ppm, more preferably 50-1000 ppm, still more preferably 50-500 ppm on the whole amount of the composition for the reconstruction of hard tissue.

It is also desirable to add a polymerization inhibitor (D) in an amount of 10-5000 ppm relative to the monomer (A).

Preparing such a composition, for example, for applying it on the body or body part, such as damaged during surgical operations area (solid fabric containing moisture, such as a biological fluid), get a composition that has excellent consumer properties, provides an appropriate request curing time and can be more stable to work than before. In addition, the composition has a high adaptability.

Although the amount of the polymerization inhibitor (D) is the same as described above, it is more preferable to add the polymerization inhibitor (D) in an amount of 50-1000 ppm, still more preferably 5 50-500 ppm no relation to the monomer (A). Thus obtained composition may, for example, not only to operate stably at the time of application, but also effectively cured after application. If the content of the polymerization inhibitor (D) is less than the lower limit of the above range, the curing occurs immediately after mixing of the monomer (A), polymer (C) and initiating polymerization to the position (S) and, therefore, the application becomes difficult. On the other hand, if the content of the polymerization inhibitor (D) exceeds the upper limit of the above range, the ability to initiate polymerization initiating the polymerization of the composition (C) is reduced and the curing period becomes longer than necessary. Therefore, medical use of the composition becomes difficult.

As one of the other components can be specified as an absorber of ultraviolet radiation. Examples of the ultraviolet absorber of radiation include:

connection benzotriazole, such as

2-(2'-hydroxy-5'-were) benzotriazol,

2-(3',5'-di-tert-butyl-2'-hydroxyphenyl)benzotriazol,

2-(5'-tert-butyl-2'-hydroxyphenyl)benzotriazol,

2-(2'-hydroxy-5'-(1,1,3,3-TETRAMETHYLBUTYL)phenyl)benzotriazole,

2-(3',5'-di-tert-butyl-2'-hydroxyphenyl)-5-chlorobenzotriazol,

2-(3'-tert-butyl-2'-hydroxy-5'-were)-5-chlorobenzotriazol,

2-(3'-sec-butyl-5'-tert-butyl-2'-hydroxyphenyl)benzotriazol,

2-(2'-hydroxy-4'-octyloxyphenyl)benzotriazole,

2-(3',5'-di-tert-amyl-2'-hydroxyphenyl)benzotriazol,

2-(3',5'-bis(α,α-dimethylbenzyl)-2'-hydroxyphenyl)benzotriazol,

2-(3'-tert-butyl-2'-hydroxy-5'-(2-octyloxyphenyl)phenyl)-5-chlorobenzotriazol,

2-(3'-tert-butyl-5'-[2-(2-ethylhexyloxy)carbonylethyl]-2'-HYDR shall xifei)-5-chlorobenzotriazol,

2-(3'-tert-butyl-2'-hydroxy-5'-(2-methoxycarbonylethyl)phenyl)-5-chlorobenzotriazol,

2-(3'-tert-butyl-2'-hydroxy-5'-(2-methoxycarbonylethyl)phenyl)benzotriazole,

2-(3'-tert-butyl-2'-hydroxy-5'-(2-octyloxyphenyl)phenyl)benzotriazol,

2-(3'-tert-butyl-5'-[2-(2-ethylhexyloxy)carbonylethyl]-2'-hydroxyphenyl) benzotriazol,

2-(3'-dodecyl-2'-hydroxy-5'-were) benzotriazole, a mixture of 2-(3'-tert-butyl-2'-hydroxy-5'-(2-isooctylmercaptoacetate)phenyl)

benzotriazole and 2,2'-methylene-bis[4-(1,1,3,3-TETRAMETHYLBUTYL)-6-benzotriazol-2-kilfenora],

the product of the interesterification reaction of 2-[3'-tert-butyl-5'-(2-methoxycarbonylethyl)-2'-hydroxyphenyl]benzotriazole with polyethylene glycol 300 and [[R-CH2CH2-COOCH2]3]2(where R is 3'-tert-butyl-4'-hydroxy-5'-2H-benzotriazol-2-ylphenyl);

compounds of benzophenone, such as

2.4 dioxybenzone, 2-hydroxy-4-methoxybenzophenone, 2-hydroxy-4-octyloxybenzophenone, 2-hydroxy-4-decyloxybenzoate, 2-hydroxy-4-dodecyloxybenzoyl, 2-hydroxy-4-benzyloxybenzophenone, 2,2', 4,4'-tetrahydroxybenzophenone and 2,2'-dihydroxy-4,4'-dimethoxybenzophenone;

4-tert-butyleneglycol, fenilsalitsilat, antifederalist, dibenzoylresorcinol, bis(4-tert-butylbenzoyl)resorcinol, benzoylation,

2,4-di-tert-butylphenyl,5-di-tert-butyl-4-hydroxybenzoate, hexadecyl 3,5-di-tert-butyl-4-HYDR who sibental, octadecyl 3,5-di-tert-butyl-4-hydroxybenzoate, 2-methyl-4,6-di-tert-butylperbenzoate and

3,5-di-tert-butyl-4-hydroxybenzylated;

steric employed amines, such as

bis(2,2,6,6-tetramethylpiperidine) sebacina,

bis(2,2,6,6-tetramethylpiperidine) succinate,

bis(1,2,2,6,6-tetramethylpiperidine) sebacina,

bis(1,2,2,6,6-pentamethylpiperidin)-n-butyl-3,5-di-tert-butyl-4-hydroxybenzyl-malonate,

the condensation product of 1-hydroxyethyl-2,2,6,6-tetrametyl-4-hydroxypiperidine and succinic acid,

the condensation products of N,N'-bis(2,2,6,6-tetramethyl-4-piperidyl) -diamine and 4-tert-octylamine-2,6-dichloro-1,3,5-8-triazine, Tris(2,2,6,6-tetramethyl-4-piperidyl)nitrilotriacetate, tetrakis(2,2,6,6-tetramethyl-4-piperidyl)-1,2,3,4 - butanoate, 1,1'-(1,2-ethandiyl) bis(3,3,5,5-tetramethylpiperidine), 4-benzoyl-2,2,6,6-tetramethylpiperidine,

4 sterilox-2,2,6,6-tetramethylpiperidine,

bis(1,2,2,6,6-pentamethyl-4-piperidyl)-2-n-butyl-2-(2-hydroxy-3,5-di-tert-butylbenzyl) malonate,

3-n-octyl-7,7,9,9-tetramethyl-1,3,8-diazaspiro [4.5] decane-2,4-dione,

bis(1-octyloxy-2,2,6,6-tetramethylpiperidine) sebacina,

bis(1-octyloxy-2,2,6,6-tetramethylpiperidine) succinate,

the condensation products of N,N'-bis (2,2,6,6-tetramethyl-4-piperidyl)-

diamine and 4-morpholino-2,6-dichloro-1,3,5-triazine,

the condensation products of 2-chloro-4,6-di(4-n-butylamino-2,2,6,6-tetramethylpiperidine)-1,3,5 resinae 1,2 - bis (3-aminopropylene)ethane,

the condensation products of 2-chloro-4,6-di(4-n-butylamino-1,2,2,6,6-pentamethylpiperidin)-1,3,5 triazine and 1,2 - bis (3-aminopropylene)ethane,

8-acetyl-3-dodecyl-7,7,9,9-tetramethyl-1,3,8-diazaspiro [4.5] decane-2,4-dione,

3-dodecyl-1-(2,2,6,6-tetramethyl-4-piperidyl)pyrrolidin-2,5-dione

3-dodecyl-1-(1,2,2,6,6-pentamethyl-4-piperidyl)pyrrolidin-2,5-dione;

connection oksamida, such as 4,4'-distractionware, 2,2'-diethoxyaniline,

2,2'-dioctyloxy-5,5'-di-tert-butylanisole, 2,2'-didodecyl-5,5'-di-tert-butylanisole, 2-ethoxy-2'-ethyloxazole, N, N '-bis (3-dimethylaminopropyl) oksamid, a mixture of 2-ethoxy-5-tert-butyl-2'-atrocinerea and 2 ethoxy-2'-ethyl-5,4'-di-tert-butylaniline, a mixture of o-methoxy - and p-methoxy-di-substituted oxanilide and a mixture of o-ethoxy - and p-ethoxy di-substituted oxanilide;

compounds 2-(-2 hydroxyphenyl)-1,3,5 triazine, such as 2,4,6-Tris-(2-hydroxy-4-octyloxyphenyl)-1,3,5 triazine,

2-(2-hydroxy-4-acyloxymethyl)-4,6-bis (2,4-dimetilfenil)-1,3,5 - triazine,

2-(2,4-dihydroxyphenyl) (2,4-dimetilfenil)-4,6-bis - 1,3,5-triazine,

2,4-bis(2-hydroxy-4-proproxyphene)-6-(2,4-dimetilfenil)-1,3,5 triazine,

2-(2-hydroxy-4-octyloxyphenyl)-4,6-bis (4-were)-1,3,5 - triazine,

2-(2-hydroxy-4-dodecyloxyphenyl)-4,6-bis (2,4-dimethanol)-1,3,5 triazine,

2-[2-hydroxy-4-(2-hydroxy-3-bullocksteads) phenyl]-4,6-bis (2,4-dimetilfenil) 1,3,5-t is Yasin,

2-[2-hydroxy-4-(2-hydroxy-3-octyloxyphenyl)phenyl]-4,6-bis(2,4-dimetilfenil)-1,3,5-triazine and

2-[4-dodecyl/tridecylamine-(2-hydroxypropyl) oxy-2-hydroxyphenyl]-4,6-bis (2,4-dimetilfenil)-1,3,5 triazine; and

the phosphites or phosphonites, such as

triphenylphosphite, diphenylacetic, phenylvaleric,

Tris(nonylphenylether), trilaurylamine, trioctadecyl,

distearoylphosphatidylcholine,Tris(2,4-di-tert-butylphenyl)FOSFA,

diisodecylphthalate, bis(2,4-di-tert-butylphenyl)pentaerythrityl,bis(2,6-di-tert-butyl-4-were)pentaerythrityl, messagelistenerthreadpool, bis (2,4-Yes-tert-butyl-6-were)pentaerythrityl, bis(2,4,6-tri-tert-butylphenyl)pentaerythrityl,christianisatiori, tetrakis(2,4-di-tert-butylphenyl)-4,4'-biphenylenediisocyanate,6-isooctane-2,4,8,10-Tetra-tert-butyl-N-dibenzo [d,g] - 1,3,2-dioxaphosphinan, 6-fluoro-2,4,8,10-Tetra-tert-butyl-12-methyldibenzo [d,g]-1,3,2-dioxaphosphinan, bis(2,4-di-tert-butyl-6-were)metaltastic and bis(2,4-di-tert-butyl-6-were)ethylphosphate.

As an absorber of ultraviolet radiation is preferred benzotriazole.

Adding absorber of ultraviolet radiation amount is preferably 10-1000 ppm, more preferably 100-800 ppm, no relation to the monomer A). Adding absorber of ultraviolet radiation is reduced staining containing monomer liquid and increases the stability of the monomer during storage.

As one of the other compounds can be specified plasticizer and softening agent.

Examples of plasticizers include:

rubbers such as natural rubbers and synthetic rubbers, and elastomers, such as thermoplastic elastomers. With such a plasticizer may be increased flexibility of the composition for the reconstruction of hard tissue.

Examples of synthetic rubbers include EPT (ethylene/propylene/terpolymer). Examples of thermoplastic elastomers include elastomers based on styrene elastomers based on vinyl chloride, elastomers based on olefins, elastomers based on polyesters, polyamide elastomers based urethanes.

The molecular weight of the elastomer is typically in the range from 1000 to 1,000,000, preferably from 2,000 to 500,000. The glass transition temperature (Tg) of the elastomer is usually not higher than 20°C., preferably not higher than 0°C.

Examples of the softeners include:

esters of hydroxycarboxylic acids, such as esters of citric acid, esters of solimano acid, esters of tartaric acid, esters of malic acid, esters of lactic acid, esters of glyceric acid is you and esters of glycolic acid; timetravel ether trimellitic acid, dibenzoate of diethylene glycol, the diethyl ester of malonic acid, triethyl o-acetylated, benzylbutylphthalate, dibenzoate dipropyleneglycol, diethylaluminum, tributyl o-acetylated, dimethylsilicone and diesters alkalophiles.

Although the amount of the softening agent is selected depending on the type of material, usually softening agent is used in such quantity that its content ranged from 0 to 30 wt%, preferably, from 0 to 20 wt%, more preferably from 0 to 10 wt%, all songs for the reconstruction of hard tissue.

As one of the other compounds can be specified preservative.

Examples of preservatives include:

methylparaben, sodium methylparaben, ethylparaben, propylparaben, sodium propylparaben, butylparaben;

the cresol, chlorocresol;

resorcinol, 4-n-hexylresorcinol, 3A, 4,7,7-tetrahydro-2-(trichloromethyl)thio)-1H-isoindole-1,3 (2H) dione;

benzalconi chloride, sodium benzalconi chloride, benzene chloride;

benzoic acid, benzyl alcohol, pyridinium chloride, chlorbutanol, dehydrator acid, o-phenylphenol, phenol, phenethyl alcohol, potassium benzoate, potassium sorbate, sodium benzoate, sodium salt dehydracetic acid, sodium propionate, sorbic acid, thimerosal, thymol, connection finalstate, such as borate of finalstate, nitrate is inistute, acetate of finalstate and formaldehyde.

As other components can then be specified anti-infective funds, antibiotics, bactericidal agent, antiviral agents, analgesic, composition analgesics, anorexicskin tools, antihelminthic drugs, anti-arthritis remedies, Antiasthmatic drugs, anticonvulsants, antidepressants, antidiuretic tools, anti-diarrhoeal remedies, antihistamines, anti-inflammatory drugs, anti-migraine, anti-emetics, anti-tumor drugs, anti-Parkinson tools, antipruritic drugs, antipsychotics, antipyretics, anti-spam tools, anticholinergics, simpatomimeticescoe means, cardiovascular drugs, antiarrhythmic drugs, antihypertensive drugs, diuretics, vasodilator, immunosuppressive drugs, muscle relaxants, parasympatholytics drugs, stimulants, sedatives, tranquilizers, cholinergic tools, chemotherapeutic drugs, radiopharmaceuticals, drugs inducing bone growth, heparin neutralizers static bladder, procoagulant, hemostatic agents, xanthine derivatives, hormones, natural proteins or sintesio the data using genetic engineering proteins, polysaccharides, glycoproteins, lipoproteins, oligonucleotides, antibodies, antigens, vasopressin, and analogues of vasopressin, epinephrine, selectin, promoting coagulation toxins, inhibitors of factor activation of plasminogen activators of platelets and synthetic peptides having hemostatic action. Due to the content of these components, the composition of the present invention can be used as drug delivery or with the aim of regenerative medicine.

Examples of microbicides include:

elemental iodine, solid iodine polyvinylpyrrolidone, polyvinylpyrrolidone iodine;

phenolic compounds, such as tribromophenol, trichlorophenol, tetrachlorophenol, NITROPHENOL, 3-methyl-4-chlorophenol, 3,5-dimethyl-4-chlorophenol, Phenoxyethanol, dichlorophen, o-phenylphenol, m-phenylphenol, p-phenylphenol, 2-benzyl-4-chlorophenol, 2,4-dichloro-3,5-dimethylphenol, 4-hartimo, chlorophen, triclosan, phenol, 2-METHYLPHENOL, 3-METHYLPHENOL, 4-METHYLPHENOL, 4-ethylphenol, 2.4 dimethylphenol, 2.5 dimethylphenol, 3.4 dimethylphenol, 2.6 dimethylphenol, 4-n-propylene, 4-n-butylphenol, 4-n-aminophenol, 4-tert-amylphenol, 4-n-hexylphenyl, 4-n-heptylphenol, monoalkylphenol, polyalkylphenol, aromatic halophenol and ammonium salts, alkali metal salts and salts of alkaline earth metals of these substances;

silver nitrate, hexachlorophene, those whom recyclin·HCl, tetracyclinee and erythromycin.

In the composition for the reconstruction of hard tissue to accelerate the recovery of the tissue may contain osteoplastic factor, etc.

As examples of the other components can then be specified odorants, such as orange oil, grapefruit oil, lemon oil, lime oil, clove oil, Wintergreen oil, peppermint oil, an alcoholic solution of peppermint, banana distillate, cucumber distillate, honey distillate, rose water, menthol, anethole, alkylsalicylate, benzaldehyde, monoglutamate sodium, ethylvanillin, thymol and vanillin.

In addition, as other components may contain an inorganic filler, organic filler, an organic composite filler, pigment filler, etc. to impart radiopaque properties and enhance properties such as adhesion strength and compressive strength.

Examples of inorganic fillers include:

powders of metal oxides such as zirconium oxide, bismuth oxide, titanium oxide, zinc oxide and aluminium oxide particles;

powders of metal salts, such as carbonate, bismuth, zirconium phosphate and barium sulfate;

the glass fillers, such as quartz glass, aluminum containing glass, barium-containing glass, transistorradio glass and glass, teramae zirconium silicate;

fillers, having a slow-release silver;

fillers, having a slow-release calcium; and

fillers, having a slow-release fluoride.

From the point of view of forming a solid connection between the inorganic filler and monomer (A) after curing, it is preferable to use the inorganic filler is subjected to surface treatment, for example, treatment with silane or polymer coating.

These inorganic fillers may be used singly or in combination of two or more types.

As examples of one of the other components can be specified radiopaque medium. Examples of such radiopaque environment include barium sulfate, zirconium oxide, bismuth carbonate, calcium tungstate, ytterbium compounds of iodine. In the present invention as a radiopaque medium zirconium oxide is preferred from the point of view of the actual results of its use for hard tissues, especially as bone cement, its high x-ray contrast properties and high dispersive ability of the pigment in comparison with barium sulphate, which also includes the results of its actual use.

Although the number of radiopaque medium vybere the SJ according to the purpose of use and so on, it usually is in the range from 10 to 70 weight parts, preferably 15-65 weight parts, per 100 parts by weight of the weight of the entire composition for the reconstruction of hard tissue, with the exception of the radiopaque medium.

Composition for recovery of the solid fabric of the present invention has high performance characteristics as agent for the reconstruction of hard tissue, i.e., consumer properties and molding or injection properties.

In this invention to obtain a composition for the reconstruction of hard tissue at first mix the monomer (A), (meth) acrylate polymer (B) initiating polymerization of the composition (C) and contained if necessary components and then the composition can be used by applying it to the damaged part. The temperature of the heat dissipation prepared above composition is usually not higher than 70°C, and the risk that may be to the detriment of the damaged tissue becomes lower.

When mixing these components, the order of mixing is not limited, but preferably, for the purpose of stability of the obtained composition for the reconstruction of hard tissue, the first monomer (A) is mixed with initiate polymerization of the composition (S) and then perform the mixing with the polymer (B).

When the composition for the reconstruction of hard tissue contains an inhibitor of p is liberizatsii (D), preferably, the monomer mixture (a) and the polymerization inhibitor (D) is first mixed with initiate polymerization of the composition (C) and then mixed with the polymer (B) to improve the stability of the obtained composition.

The cured product obtained from the composition for the reconstruction of hard tissue is formed within 24 hours after preparation of the composition, and has a thickness of not less than 0.1 μm, a length of not less than 25 mm and a width of not less than 2 mm, preferably, has a flexible elastic modulus measured at a testing speed of 2 mm/min, not less than 100 MPa, preferably has a tensile strength measured at a testing speed of 1 mm/min, not less than 10 MPa and preferably has a Flexural strength, measured at a testing speed of not less than 2 mm/min, not less than 10 MPa.

Flexible elastic modulus of the above-mentioned cured product may preferably be not less than 100 MPa, more preferably not less than 150 MPa, more preferably not less than 200 MPa.

When the composition for the reconstruction of hard tissue contains radiopaque environment, the cured product obtained from the composition for the reconstruction of hard tissue is formed within 24 hours after preparation of the composition, and has a thickness of not less than 0.5 μm, a length of not less than 25 mm and a width of 2 mm, predpochtite is) has a flexible elastic modulus measured at a testing speed of 2 mm/min, not less than 1800 MPa, more preferably not less than 2000 MPa, more preferably not less than 2200 MPa, and preferably has a Flexural strength, measured at a testing speed of 2 m/min, not less than 50 MPa

Further, the vulcanized product obtained from the composition for the reconstruction of hard tissue, repairs, formed after 24 hours after preparation of the composition, preferably has a shear strength of not less than 10 MPa (test speed: 2 mm/min). In addition, this cured product preferably has a compressive strength of not less than 10 MPa (test speed: 2 mm/min). When the composition for the reconstruction of hard tissue contains radiopaque medium, a vulcanized product obtained from the composition for the reconstruction of hard tissue formed after 24 hours after preparation of the composition and has a thickness of 5 mm, a length of 10 mm and width 10 mm, preferably has a compressive strength measured at a testing speed of 2 mm/min, not less than 70 MPa, more preferably not less than 75 MPa.

Composition for the reconstruction of hard tissue has exceptional adhesion between the solid fabrics, filling in solid tissues, adhesion between the solid fabrics and artificial the materials, such as titanium, ceramics and stainless steel, the adhesion between the solid tissues and other tissues, such as soft tissue, and so on, except for dental use.

The film, which is obtained from the composition for the reconstruction of hard tissue is formed within 24 hours after preparation of the composition and has a thickness of not less than 1 μm (preferably not more than 1 cm), length not less than 25 mm and a width of not less than 2 mm, may, preferably, have an elongation at tensile strength, measured at a testing speed of 1 mm/min, at least 30%, more preferably at least 40%, even more preferably not less than 50%.

When the composition for the reconstruction of hard tissue contains radiopaque environment, the cured product obtained from the composition for the reconstruction of hard tissue, is given 24 hours after preparation of the composition and has a thickness of 0.5 mm, a length of 25 mm and a width of 2 mm, preferably has a tensile strength, as measured under the conditions of test coefficient of 1 mm/min, not less than 30 MPa, more preferably not less than 31 MPa.

Accordingly, the composition of the present invention is favorable for the reconstruction of hard tissue.

Composition for repair of hard tissues of the present invention has a viscosity of from 0.4 to 2000000 SP within 30 seconds the settlement of the E. mixing components (A), (B) and (C) and contained, if necessary, other components.

When the viscosity is in the above range, the composition has high performance characteristics, for example, can easily be the use of a composition for the repair of hard tissue, or injection, or casting composition for filling bone.

From the point of view of operational properties and fluidity, it is preferable viscosity in the range 0.4-500000 JV, more preferred 1-500000 SP.

Composition for recovery of the solid fabric of the present invention preferably has a viscosity of from 1 to 2000000 SP, more preferably 10-2000000 SP 60 seconds after mixing of components (A), (b) and (C) and contained, if necessary, other components.

Next, the composition for recovery of the solid fabric of the present invention preferably has a viscosity of from 10 to 80000000 JV, more preferably from 50 to 50000000 SP, even more preferably from 100 to 20000000 JV after 540 seconds after mixing of components (A), (b) and (C) and contained, if necessary, other components.

Since the viscosity is in the above range, the composition has high performance characteristics, for example, can easily be the use of a composition for the repair of hard tissue or transfusion of composition in cement the Yu gun for filling bone or injection of the composition into the bone.

Before or during curing of the composition to recover a solid fabric of the present invention the composition may be subjected to irradiation with electromagnetic waves such as visible light, ionizing radiation (for example, γ - rays or electron rays, with the purpose of sterilization. Sometimes it is desirable irradiation of visible light as visible light does not significantly change the conditions of curing. Sterilization can be performed by processing gas, such as dry heat, steam, ethylene oxide (EO) or hydrogen peroxide, filtering, processing liquid, autoclave sterilization, etc.

Before applying the composition to recover a solid fabric of the present invention on the damaged part of the body, the damaged part can be disinfected with a disinfectant, such as alcohol.

In order to enhance adhesion to the damaged part of the body before applying the composition to recover a solid fabric of the present invention on the damaged part can be carried out pre-processing. The liquid pre-processing is, for example, an aqueous solution containing 1-15% by weight. citric acid and 1-5 wt%. iron chloride (III).

If there are concerns that the form or characteristics of performance, composition for recovery of the solid fabric of the present invention are changed during a long the wow time thus deteriorating the effect of the present invention, it is possible that all components, including the monomer (A), (meth)acrylate polymer (B) initiating polymerization of the composition (C) and contained if necessary components, which are used for the reconstruction of hard tissue, stored in the form of a set for the reconstruction of hard tissue, which has two or more containers, which contained the above-mentioned components separately or divided into optimal combinations of groups, and which before use, mix with the formation of the composition for the reconstruction of hard tissue. Containers for placing components are, for example, a sealed gas-tight rubber containers to prevent evaporation or dispersion of the monomer (a) and initiate polymerization of the composition (C) or glass syringes. Tanks for posting polymer (B) are, for example, rubber containers, with good sealing properties, or glass containers, to prevent absorption of moisture. With regard to place quantities, in some cases, placed this amount that will be spent at one time, or cases where put this number that is used for several times.

Examples of methods of storage components include the method where the components are divided into three groups which, consisting of a mixture of component (a) and contained if necessary components of the mixture of the component (C) is contained, if necessary, components and mixture of the component (C) is contained, if necessary, components and their subsequent storage; the method, where the components are divided into two groups consisting of a mixture of component (A) with component (b) and contained, if necessary, components, and component (C), and their subsequent storage; the method, where the components are divided into two groups consisting of a mixture of component (A) component (b) and a mixture of the component (C) is contained, if necessary, components, and their subsequent storage; the method, where the components are divided into two groups consisting of a mixture of component (A) with component (b) and part contained, if necessary, components and mixture of the component (C) with the remainder contained, if necessary, components, and their subsequent storage; the method, where the components are divided into two groups consisting of a mixture of component (a) is contained, if necessary, components and mixture of the component (C) component (C) With their subsequent storage; and the way in which the components are divided into two groups, consisting of component (A) and a mixture of the component (C) with component (C) and contained if necessary components and their subsequent storage; the method in which the components are divided into two groups consisting of a mixture of component (a) contained in part if necessary components and of the mixture of the component (C) with component (C) and the remainder is contained, if necessary, components, and their subsequent storage.

In the case when contains the polymerization inhibitor (D), examples of the storage methods include a method in which the components are divided into three groups, consisting of a mixture of component (a) contained if necessary components. a mixture of the component (C) is contained, if necessary, components and mixture of the component (C) is contained, if necessary, components and their subsequent storage; the way in which the components are divided into two groups consisting of a mixture of component (A) with component (B), component (D) and containing, if necessary, components and component (C) With their subsequent storage; the way in which the components are divided into two groups consisting of a mixture of component (A) with component (b) and component (D) and the mixture of the component (C) is contained, if necessary, components and their subsequent storage; the way in which the components of profit into two groups, consisting of a mixture of component (A) with component (B), component (D) and part contained, if necessary, components and mixture of the component (C) with astatke is contained, if necessary, components and their subsequent storage; the way in which the components are divided into two groups consisting of a mixture of component (A) with component (D) and containing, if necessary, components and mixture of the component (C) with component (C) With their subsequent storage; the way in which the components are divided into two groups consisting of a mixture of component (A) with component (D) and a mixture of the component (C) with component (C) and containing, if necessary, components and their subsequent storage; and the way in which the components are divided into two groups consisting of a mixture of component (A) with component (D) and part contained, if necessary, components and mixture of the component (C) with component (C) and with the remainder contained, if necessary, components and their subsequent storage.

In addition to the above methods, when the monomer (A) use a mixture of the monomer having the acid group with a monomer having no acidic group, the components can be stored in such a way that the monomer having an acid group is not in contact with the initiating polymerization of the composition. Examples of such method include a method in which the components are divided into two groups consisting of a mixture of the monomer having an acid group, component (b) and containing, if necessary, components and mixtures of monomer not having an acid group to which momentum (S) with their subsequent storage; the way in which the components are divided into two groups consisting of a mixture of the monomer having an acid group, component (b) and a mixture of the monomer having no acid group, component (C) and containing, if necessary, components and their subsequent storage; the way in which the components are divided into two groups consisting of a mixture of the monomer having an acid group is contained, if necessary, the components and of the mixture of the monomer having no acid group, component (b) and component (C) With their subsequent storage; and the way in which the components are divided into two groups consisting of a monomer having an acid group, and a mixture of the monomer having no acid group, component (B), component (Q and contained, if necessary, components, and their subsequent storage.

Divided into two groups of components are placed in a separate container, for example, in containers, such as syringes and containers are combined into a set, which is used for the reconstruction of hard tissue and which can be executed as a product.

The dial design is not specifically limited, provided that there is no possibility of changing the shape or performance of the components during storage and thereby causing damage to the present invention, but preferably the set is of such a construction, when the cat is Roy monomer (A), the polymer (b) and initiate polymerization of the composition (S) are placed separately, and the first monomer (A) is mixed with initiate polymerization of the composition (C) containing an organoboron compound, and then mixed with the polymer (B). With this design provides a composition for the reconstruction of hard tissue with more stable performance.

Sets examples for the reconstruction of hard tissue include:

set with capacity (e.g., containers, syringes), in which the monomer (A), the polymer (b) and initiate polymerization of the composition (S) each independently are placed separately, and have the capacity (e.g., vessel or bowl for mixing) in order to extract placed in a container components and mix them; and

set with one container that has three or more chambers separated by partitions in said chambers independently placed the monomer (A), the polymer (b) and initiate polymerization of the composition (C), and having a mixer for mixing the monomer (a) and initiate polymerization of the composition (C) with polymer (B), and said components (a) and (C) pass through the bypass formed in the container by perforation or move partitions.

When set contains the polymerization inhibitor (D), the set preferably has such a structure, the which the mixture containing the monomer (a) and the polymerization inhibitor (D), the polymer (b) and initiate polymerization of the composition, each independently housed separately, and the mixture containing the monomer (a) and the polymerization inhibitor (D), first mixed with initiate polymerization of the composition (C) containing an organoboron compound, and then mixed with the polymer (B). Due to this structure provides a composition for the reconstruction of hard tissue, with more stable performance.

Examples of such sets include:

set with capacity (e.g., containers, syringes), in which a mixture containing the monomer (a) and the polymerization inhibitor (D), the polymer (b) and initiate polymerization of the composition (C), each independently housed separately, and have the capacity (e.g., vessel or bowl for mixing) in order to extract placed in a container components and mix them; and

set with one container that has three or more chambers separated by partitions in said chambers independently placed a mixture containing the monomer (a) and the polymerization inhibitor (D), the polymer (b) and initiate polymerization of the composition (C), and having a mixer for mixing a mixture containing the monomer (a) and the polymerization inhibitor (D) and initiate polymerization of the composition (C) with polymer (B), being the m the specified mix and the specified component (S), pass through the bypass formed in the container by perforation or move partitions.

Set with one container, where the components are placed in a separate three or more cameras, requires fewer operations than the means, where the composition of the present invention separated, placed in two or more containers, usually in containers, and mixed immediately before use. In addition, this set does not contain a mixing tank, etc., and is cheap, because from the container take the required amount of composition and applied to a suitable device for use, for example, a sponge.

It is also possible that a device that is used to apply the composition to the reconstruction of hard tissue at the damaged part of the body, for example, solid tissue, such as bone or cartilage, soft tissue or synthetic material, such as titanium, ceramics or stainless steel, in advance contains part or all of initiating the polymerization of the composition (S) and the device is brought into contact with the monomer (A) or the mixture containing the monomer (a) and the polymerization inhibitor (D), the polymer (B) and contained if necessary components to obtain the composition for recovery of the solid fabric of the present invention in situ and then using it on the damaged part of the A.

Examples of such devices for applying the composition to the damaged parts of the body include the brush, fiber ball, cloth, sponge ball or a piece of sponge.

Set for the reconstruction of hard tissue may include the above disinfectant liquid, such as alcohol, the above solution for pre-treatment to improve the adhesion and so on

When the components of the composition is stored in a set, they can be subjected to sterilization using electromagnetic waves such as visible light, preferably in the conditions under which the components are not modified (for example, a monomer not cures).

Composition for recovery of the solid fabric of the present invention can be used as a bone cement, which is used for adhesion between hard tissues, filling of hard tissues, adhesion between hard tissue and artificial materials such as titanium, ceramics and stainless steel, the adhesion between the solid tissues and other tissues, such as soft tissue fixation hard tissues such as bone and cartilage, artificial joints, and so on, or can be used as a filler for bone defects of material for replacement of bone, artificial bone, etc.

Examples

Further, the present invention is described with reference to the following examples that the E. limit the invention.

Examples 1A-10A, Comparative Examples 1A and 2A

Reagents

As the monomer (A), polymer (b) and initiate polymerization of the composition (C) in the examples you used the following compounds and compositions.

The monomer (A): 4-META/MMA, methylmethacrylate solution of the anhydride of 4-methacryloxypropyltrimethoxy acid (weight ratio: approximately 5%).

The polymer (C): a mixture of three kinds of the following emission spectra obtained for pure (polymetylmetacrylate) (b1) (b3) and pigment.

The weight ratio of these components is the following: 100 weight parts of the total amount of the three kinds of emission spectra obtained for pure and pigment (b1) is contained in the number 20,03 weight parts, (b2) is contained in an amount of 62.5 parts by weight of (b3) is contained in the amount of 12.5 weight parts and the pigment - rest.

Molecular weight and properties of the emission spectra obtained for pure (1)-(3) of the following:

(b1) srednevekovoi molecular weight: 450000, volumetric average diameter of particles: 26,7 μm, specific surface area: 2,913 m2/g

(b2) srednevekovoi molecular weight: 140000, volumetric average diameter of particles:

of 8.2 μm, specific surface area: 0,827 m2/g

(b3) srednevekovoi molecular weight: 140000, volumetric average diameter of particles:

24,6 μm, specific surface area: 0,371 m2/year

Volumetric average diameter of the particles of the emission spectra obtained for pure (refractive index: 1,49) was measured as follows. As the dispersion medium used special reaction the willows - methanol brand net (refractive index: 1,33 obtained from Wako Pure Chemical IndusTpnes, Ltd.). Emission spectra obtained for pure was dispersively in the dispersion medium using an ultrasonic homogenizer for 5 minutes (output: 25 watts) and carried out the measurement at a circulation rate of 50% (100%: 65 ml/s) using a Microtrac MCSTEP (measuring the distribution of particle size production Microtrac hie.).

Specific surface area was determined by absorption of gaseous nitrogen at liquid nitrogen temperature (77 K) using Autosorb 3 (manufactured by Quantachrome Instruments), and was measured by the BET method (method of brunauer-Emmett-teller).

Initiate polymerization of the composition (C): type TBB, namely, partially oxidized tributive: 80 weight parts, hexane: 19 weight parts ethanol: 1 weight part.

Determination of the viscosity

In the sampling tube was weighed polymer (B) in accordance with the ratio of components in the mixture described in Examples 1A-6A and Comparative Example 1A, the following Table 1. Into the sample tube, which was weighed polymer (B) was injected monomer (a) and initiate polymerization of the composition (C), which were mixed together in another sample tube in accordance with the ratio of components in the mixture described in Examples 1 AND 6A and Comparative Example 1A, the following Table 1 as above, and were mixed together at 25°With Poluchenie adhesive composition of the present invention. Within 30 seconds after receiving the measured viscosity of the composition. The viscosity at the time of receipt was not less than 0.4 JV and it was confirmed that over time the viscosity increased. The viscosity was measured using a conventional viscometer, type E (manufactured by Tokyo Keiki Inc., type ENR), at 25°C. the Results of determination are shown in Table 1.

Assessment of operational properties

In the syringe with the cap in Swarovski part, was slapped in the polymer (B) in accordance with the ratio of components in the mixture described in Examples 1A-6A and Comparative Example 1A, the following Table 1. In this syringe was injected monomer (a) and initiate polymerization of the composition (C), which were mixed together in the sampling tube in accordance with the ratio of components in the mixture described in Examples 1A-6A and Comparative Example 1A, the following Table 1, as mentioned above and mixed together at 25°C. Then the syringe was removed the lid, set the nozzle having a width of 1 cm and a thickness of 1 mm, and 1 ml of the mixed composition was applied in the form of 4 cm on a plastic sheet. Operational properties were evaluated on a 5-point system from 1 to 5. The case where the width of the applied composition was not less than 1 cm but less than 1.2 cm, was estimated at 5; the case where the width of the applied composition was not less than 1.2 cm but less than 1.4 cm, was estimated to be 4; the case where the Irina applied composition was not less than 1.4 cm, but less than 1.6 cm, was estimated at 3; the case where the width of the applied composition was not less than 1.6 cm, was estimated at 2; and the case where the application was impossible, was estimated at 1. The evaluation results are shown in Table 1.

Evaluation of extrusion from the container

In the syringe, the outlet of which was closed with a lid, was slapped in the polymer (B) in accordance with the mixing ratio described in Examples 1A-6A and Comparative Example 1A, the following Table 1. In a syringe, in which was placed the polymer (B) was injected monomer (a) and initiate polymerization of the composition (C), which were mixed together in the sampling tube in accordance with the mixing ratio described in Examples 1A-6A and Comparative Example 1 the following Table 1 as stated above, and was mixed at 25°C. Then the cap from the syringe, in which were placed the three components (A), (b) and (C), deleted, installed 11G needle and 1 ml of the mixed composition was squeezed out on a sheet of polyethylene. The extrusion was evaluated by 3-point scale ranging from 1 to 3. The case where the entire quantity of the composition was squeezed out for 20 seconds at a pressure of 50 kPa was estimated at 3; the case where the entire quantity of the composition was extruded at least 20 seconds, but less than 60 seconds, was estimated at 2; and the case where the entire quantity of the composition was not pressed even not less than 60 Sekou is d, was estimated at 1. The evaluation results are shown in Table 1.

Table 1
Adhesive composition (weight parts)Viscosity through
30 s after mixing (JV)
Service
nye properties
Extrusion from the container
Ave.1AThe monomer (A): 1680 mg (87.2) Polymer (In): 192.7 mg (10.0) initiate polymerization of the composition (C): 54 mg (2.8)0.523
Ave.2AThe monomer (A): 1680 mg (82.4) Polymer (In): 192.7 mg(15.0) initiate polymerization of the composition (C): 54 mg (2.6)43
Ave. 3AThe monomer (A): 1680 mg (77.5) Polymer (In): 433.5 mg (20.0) initiate polymerization of the composition (C): 54 mg (2.5)2443
Ave.4AThe monomer(A): 1680 mg (67.8) On the emer (In): 743.1 mg (30.0) initiate polymerization of the composition (C): 54 mg (2.2) 4053
Ave.5AThe monomer(A): 1680 mg (58.1) Polymer (In): 1156 mg (40.0) initiate polymerization of the composition (C): 54 mg (1.9)16453
Ave.6AThe monomer(A): 1680 mg (48.4) Polymer (In): 1734 mg (50.0) initiate polymerization of the composition (C): 54 mg (1.6)256053
EUR. Ave.1AThe monomer(A): 1680 mg (19.4) Polymer (In): 6939 mg (80.0) initiate polymerization of the composition (C): 54 mg (0.6)Immeasurable

Evaluation of flexible elastic modulus, tensile strength and the Flexural.

A 5 ml sample tube was weighed polymer (B) in accordance with the ratio of components in the mixture described in Examples 7A-9A the following Table 2. Into the sample tube, which was weighed polymer (B) was injected liquid mixture of monomer (a) and initiate polymerization of the composition (C), which was prepared in another sample tube of 1 m is in accordance with the ratio of components in the mixture, described in Examples 7A-9A the following Table 1 as above, and were mixed together at 25°C for 5 seconds using a glass rod to obtain a homogeneous mixture.

The resulting composition was injected into the syringe and immediately filled the frame in order to prepare a sample of the cured product in accordance with the following procedure, as shown in Fig.1.

The glass plate was placed in the following order sheet RE Lumirror (trade mark) and the fluorine-rubber frame, having a thickness of 0.5 mm (inside dimension of frame: 25 mm (length) × 2 mm (width)). This frame was filled with the prepared composition for the reconstruction of hard tissue. The filling is carried out so that no air bubbles. After filling later on it was applied in the specified order sheet RE Lumirror (trade mark) and a glass plate and the four corners of the two outer plates were fixed with clamps. Then kept for 24 hours at 25°C (room temperature) and then took the cured product from the frame. If the surface of the obtained cured product had irregularities, the surface was cleaned waterproof abrasive sandpaper #600 to remove irregularities and received a sample of the cured product. The obtained cured product had a size with a length of 25 mm, a width of 2 mm and a thickness of 0.5 mm.

Flex is the first modulus of elasticity (test speed: 2 mm/min), the tensile strength (test speed: 1 mm/min) Flexural strength (test speed: 2 mm/min) of the cured product was determined 24 hours after preparation with EzTest/CE, the production of Shimadzu Corporation. Each value was measured as the average value for the four samples. The evaluation results are shown in Table 2.

Evaluation of compressive strength

A 5 ml sample tube was weighed polymer (B) in accordance with the ratio of components in the mixture described in Examples 7A-9A the following Table 2. Into the sample tube, which was weighed polymer (B) was injected liquid mixture of monomer (a) and initiate polymerization of the composition (C), which was prepared in another sample tube 1 ml in accordance with the ratio of components in the mixture described in Examples 7A-9A the following Table 1 as above, and were mixed together at 25°C for 5 seconds using a glass rod to obtain a homogeneous mixture.

From the obtained composition was prepared cured product having a size of 4.0 mm × 4.0 mm × 3.0 mm, and the cured product 6 mm (diameter) × 8 mm (length). 24 hours after the preparation was measured compressive strength (testing speed: 2 m/min) using an Autograph (DSS500, production Shimadzu Corporation). The results are shown in Table 2.

Table 2
Adhesive composition (weight parts)Flexible elastic modulus (MPa)Tensile strength (MPa)Compressive strength (MPa)Flexural strength (MPa)
Ave.7AThe monomer (A): 586 mg (66.6) Polymer (In): 262 mg (29.7) initiate polymerization of the composition (C): 33 mg (3.7)420305550
Ave.8AThe monomer (A): 586 mg (51.2) Polymer (In): 525 mg (45.9) initiate polymerization of the composition (C): 33 mg (2.9)540266060
Ave.9AThe monomer (A): 586 mg (32.6) Polymer (In): 1180 mg (65.6) initiate polymerization of the composition (C): 33 mg (1.8)1500506367

Exothermic properties

A 30 ml sample tube was weighed polymer (b) and barium sulfate (obtained from Wako Pure Chemicl Industries, Ltd.) in accordance with the ratio of components in the mixture described in Example 10A. Then a 10 ml sample tube was weighed solution of the monomer (a) and initiate polymerization of the composition (C) in accordance with the ratio of components in the mixture described in Example 10A similar to the above and mixed components. The mixture was introduced into the sample tube, which was weighed polymer, and mixed together at 25°C for 1 minute, using a glass rod to obtain a homogeneous mixture. Then the mixture was placed in a cylindrical container having a diameter of 30 mm and a height of 15 mm, and in the Central part of the mixture was put in a thermometer to measure the temperature.

An example of a case where the polymerization initiator used benzoyl peroxide (obtained from Wako Pure Chemical Industries, Ltd.), shown as a Comparative Example 2A. In chemical beaker 100 ml was weighed polymer (B), barium sulfate and benzoyl peroxide in accordance with the mixing ratio described in Comparative Example 2A. In this glass is injected with a solution of monomer (A) was mixed at 25°C for 1 minute, using a glass rod to obtain a homogeneous mixture. Then the mixture was placed in a cylindrical container having a diameter of 30 mm and a height of 15 mm, and in the Central part of the mixture was put in a thermometer to measure the temperature.

The results bring the us in Table 3. As for the composition, prepared from a monomer (A), polymer (b) and initiate polymerization of the composition (C), the temperature began to rise immediately after mixing and the highest temperature was relatively low. On the other hand, in the case of using as a polymerization initiator benzoyl peroxide, it took a relatively long time before the temperature began to rise, and after the start of raising the temperature rapidly increased for a short time. In addition, the highest temperature was higher than the highest temperature in the case of compositions prepared from monomer (A), polymer (b) and initiate polymerization of the composition (S).

Table 3
Adhesive composition (weight parts)Temperature
Ave.10AThe monomer (A): 20 g (27.7) Polymer (In): 48 g (66.4) initiate polymerization of the composition (C): 0.9 g (1.2) barium Sulfate: 3.4 g (4.7)Immediately after mixing, the temperature is mildly increased in 5 minutes 30 seconds to 30°C, and then relatively quickly rose to reach the highest temperature of 60°C for 7 minutes and 30 CE is und after mixing and then slowly went down.
EUR. Ave.2AThe monomer (A): 20 g (30.6) Polymer (In): 40 g (61.2) initiate polymerization of the composition (C): 0.4 g (0.6) barium Sulfate: 5.0 g (7.6)After mixing temperature for 6 minutes slowly increased, then gently reached 30°C for 9 minutes after mixing, after quickly increased to reach the highest temperature 85°C for 9 minutes 30 seconds after mixing and then slowly went down.

Assessment of the strength of adhesion

On the cortical layer of the femur dogs were set at right angles polyacrylic rod having a diameter of 5 mm, using a composition obtained by mixing components in accordance with the ratio in the mixture described in Example 10A, and was immersed in water at 37°C for 24 hours followed by implementation of test for exfoliation of the acrylic block from the bone using an Autograph (DSS500, production Shimadzu Corporation). As a result, the adhesion strength was 10 MPa.

Examples 1B-13B, Comparative Examples 1B-13B

In the following examples and comparative examples used the same monomer (A) and the same initiate polymerization of the composition (C) as in the above examples. As the polymer (C) used a mixture obtained by mixing the above-mentioned polymers (b1), (b2) and (b3) in the ratio the AI components of the mixture, described in the following Tables 4-11. As a radiopaque medium used zirconium oxide obtained from Daiichi Kigenso Depending Kogyo Co., Ltd. The mixing of the polymers (b1), (b2) and (b3) with zirconium oxide was performed using rocking the turbula (type TS, production of Willy A. Bachofen AG) for 30 minutes at 23±1°C.

Assessment of homogeneity of variance

In a polypropylene container having an inner diameter of 2.5 cm and a depth of 1 cm, was slapped in the polymer (b) and zirconium oxide in accordance with the mixing ratio of Examples 1B-13B and Comparative Examples 1B-13B, described in the following Tables 4-11. In this plastic container inject the monomer (a) and initiate polymerization of the composition (C), which were mixed together in 10 ml glass sample tube in accordance with the ratio of components in the mixture described in Examples 1B-13B and Comparative Examples 1B-13B the following Tables 4-11, as mentioned above and mixed together in a polypropylene spatula at 25°C for 20 seconds. After that, the state of the mixture in the container was evaluated by visual observation. The evaluation was performed as follows. The case where the powder of the polymer (B) could not be mixed, was estimated as 0; the case where there has been a large amount of undissolved powder was evaluated as 1; the case where the mixture lacked the fluidity and was in klinoobrazno dissolved with the state of was estimated as 2; and the case where the mixture had a fluidity and was dissolved, was estimated as 3. The evaluation results are shown in Table 7. In the case of 0 could not be prepared any sample for testing, and therefore, other assessments were not performed. The evaluation results are shown in tables 4-11.

The homogeneity of variance of contrast media environments

In a polypropylene container having an inner diameter of 2.5 cm and a depth of 1 cm, was slapped in the polymer (b) and zirconium oxide in accordance with the mixing ratio of Examples 1B-13B and Comparative Examples 1B-13B, described in the following Tables 4-11 same as described above. In this plastic container inject the monomer (a) and initiate polymerization of the composition (C), which were mixed together in 10 ml glass sample tube in accordance with the ratio of components in the mixture described in Examples 1B-13B and Comparative Examples 1B-13B the following Tables 4-11, as mentioned above and mixed together in a polypropylene spatula at 25°C for 20 seconds. After that, the state of the mixture in the container was evaluated by visual observation under stirring with a spatula and dripping from the pipette. The evaluation was performed as follows. The case when the observed sediment radiopaque medium in the polymer (B) was estimated as 0; the case when the residue of the rent is encontraste environment was observed, but it was not visible under stirring with a spatula for 20 seconds, was estimated as 1; and the case when the sediment x-ray contrast medium was not observed under stirring, was estimated as 2. The evaluation results are shown in tables 4-11.

The estimation of the initial viscosity

In a polypropylene container having an inner diameter of 2.5 cm and a depth of 1 cm, was slapped in the polymer (b) and zirconium oxide in accordance with the mixing ratio of Examples 1B-13B and Comparative Examples 1B-13B, described in the following Tables 4-11. In this plastic container inject the monomer (a) and initiate polymerization of the composition (C), which were mixed together in 10 ml glass sample tube in accordance with the ratio of components in the mixture described in Examples 1B-13B and Comparative Examples 1B-13B the following Tables 4-11, as mentioned above and mixed together in a polypropylene spatula at 25°C for 20 seconds. 60 seconds after mixing was measured viscosity at 25°C using a capillary viscometer (manufactured by HAAKE, RS150.). It was confirmed that the viscosity will increase with time. The evaluation results are shown in Tables 4-11.

Assessment of operational properties

In a polypropylene container having an inner diameter of 2.5 cm and a depth of 1 cm, was slapped in the polymer (b) and zirconium oxide in accordance with the rate of mixture components of Examples 1B-13B and Comparative Examples 1B-13B, described in the following Tables 4-11. In this plastic container inject the monomer (a) and initiate polymerization of the composition (C), which were mixed together in 10 ml glass sample tube in accordance with the ratio of components in the mixture described in Examples 1B-13B and Comparative Examples 1B-13B the following Tables 4-11, as mentioned above and mixed together in a polypropylene spatula at 25°C for 20 seconds. After 540 seconds after mixing was measured viscosity at 25°C using a capillary viscometer (manufactured by HAAKE, RS150.). It was confirmed that the viscosity will increase with time. The evaluation was performed as follows. The case where the viscosity is not less than 80000×103JV, was estimated as 0; the case where the viscosity was in the range of 80000×103JV to 50000×103JV, was estimated as 1; the case where the viscosity was in the range of 50000×103SP-20000×103JV, was estimated as 2; and the case where the viscosity of not more than 20000×103JV, was estimated as 3. The evaluation results are shown in Tables 4-11.

Evaluation of mechanical properties

(1) a Flexible elastic modulus, Flexural strength and tensile strength

In a polypropylene container having an inner diameter of 2.5 cm and a depth of 1 cm, was slapped in the polymer (b) and zirconium oxide in accordance with the mixing ratio of the Use the and 1B, Example 2B Example 8B, Comparative Example 1B and Comparative Example 2, Comparative Example 4 and Comparative Examples 6V-9V, described in the following Tables 4-11. In this plastic container inject the monomer (a) and initiate polymerization of the composition (C), which were mixed together in 10 ml glass sample tube in accordance with the ratio of components in the mixture of the above-described examples and Comparative Examples, the following Tables 4-11, as mentioned above and mixed together in a polypropylene spatula at 25°C for 20 seconds. The mixture was immediately filled the frame in order to prepare a sample of the cured product in accordance with the following procedure, as shown in Fig.1.

The glass plate was placed in the following order sheet RE Lumirror (trade mark) and the fluorine-rubber frame, having a thickness of 0.5 mm (inside dimension of frame: 25 mm (length) × 2 mm (width)). This frame was filled with the prepared composition for the reconstruction of hard tissue. The filling is carried out so that no air bubbles. After filling later on it was applied in the specified order sheet RE Lumirror (trade mark) and a glass plate and the four corners of the two outer plates were fixed with clamps. Then kept for 24 hours at 25°C (room temperature) and then in the occupy the cured product from the frame. If the surface of the obtained cured product had irregularities, the surface was cleaned waterproof abrasive sandpaper #600 to remove irregularities and received a sample of the cured product. The obtained cured product had a size with a length of 25 mm, a width of 2 mm and a thickness of 0.5 mm.

Flexible elastic modulus (test speed: 2 mm/min) tensile strength (test speed: 1 mm/min) Flexural strength (test speed: 2 mm/min) of the cured product was determined 24 hours after preparation with the help of Avtograf (EZ-S, production Shimadzu Corporation). Each value was measured as the average value for the four samples. The evaluation results are shown in Tables 4-11.

The valuation was carried out as follows. The case where a flexible elastic modulus was not less than 1800 MPa, Flexural strength was not less than 50 MPa and the tensile strength was not less than 30 MPa was evaluated as a passing score. The case when the contrast medium was not a homogeneous dispersion and homogeneous sample of the cured product was not received, was regarded as immeasurable. The evaluation results are shown in Tables 4-11.

(2) evaluation of the compressive strength

In a polypropylene container having an inner diameter of 2.5 cm and a depth of 1 cm, was slapped in the polymer (b) and oxide is zirconium in accordance with the ratio of components of the mixture of Example 2B, Example 8B, Comparative Example 1B and Comparative Example 2 and Comparative Example 6B, described in the following Tables 4-11. In this plastic container inject the monomer (a) and initiate polymerization of the composition (C), which were mixed together in 10 ml glass probational tube in accordance with the ratio of components in the mixture of the above-described examples and Comparative Examples, the following Tables 4-11, as mentioned above and mixed together in a polypropylene spatula at 25°C for 20 seconds. The glass plate was placed in the following order sheet RE Lumirror (trade mark) and silicone frame, having a thickness of 5 mm (inside dimension of frame: 10 mm (length) × 10 mm (width)) in the order as shown in Fig.2. This frame was filled with the prepared composition for the reconstruction of hard tissue. The filling is carried out so that no air bubbles. After filling later on it was applied in the specified order sheet RE Lumirror (trade mark) and a glass plate and top with cargo 200, then kept for 24 hours at 25°C (room temperature), then took the cured product from the frame and thus received the cured product. If the surface of the obtained cured product had irregularities, the surface was cleaned waterproof abrasive sandpaper #600 is La removal of irregularities. 24 hours after preparation was measured compressive strength of the cured product using a precision universal testing machine (type 2100, production Intesco Co., Ltd.) when testing speed of 2 mm/min at 23±1°C. Evaluation was made as follows. The case where the compressive strength was not less than 70 MPa, was regarded as a passing grade. The case where no point of critical flow was not observed was evaluated as immeasurably. The evaluation results are shown in Tables 4-11.

The overall score

Case when homogeneity of variance was not less than 2, the homogeneity of the dispersion x-ray contrast medium was not less than 1, the initial viscosity, i.e. the viscosity after 60 seconds was in the range of 10 to 2000000 SP, operational properties were evaluated as 3 and the mechanical properties were regarded as a passing grade, was evaluated as AA; case, where homogeneity of variance was not less than 1, the uniformity of dispersion x-ray contrast medium was not less than 1, the viscosity after 60 seconds was in the range of 10 to 2000000 SP, operational properties were not less than 2 and the mechanical properties were regarded as a passing grade, was evaluated as A; the case where homogeneity of variance was not less than 1, the uniformity of dispersion x-ray contrast medium was not less than 1, the viscosity after 60 seconds was di is the range from 10 to 2000000 SP, operational properties were not less than 1 and the mechanical properties were regarded as a passing grade, was evaluated as a; the case where the solubility was 0, or the case where homogeneity of variance was 0, or the case where the uniformity of dispersion x-ray contrast medium was 0, or the case when the viscosity after 60 seconds went beyond 10-2000000 JV, or the case where the operational properties were 0, or the case where the mechanical properties were regarded as insufficient, were evaluated as C. the Evaluation results are shown in Tables 4-11.

The reference list of items

11: glass plate, 12: Lumirror (trade mark), 13: fluoro-rubber frame (the Central white part indicates the space of 25 mm (length) × 2 mm (width), which is filled with liquid mixture of a solution of monomer (A), polymer (b) and initiate polymerization of the composition (C).)

21: glass plate, 22: Lumirror (trade mark), 23: silicone frame (the Central white part specifies a space of 10 mm (length) × 10 mm (width) × 5 mm (thickness), which is filled with liquid mixture of a solution of monomer (A), polymer (b) and initiate polymerization of the composition (C).)

1. Composition for the reconstruction of hard tissue, comprising from 5 to 98,95 parts by weight of methacrylate (A), from 37.9 to 75 parts by weight of unstitched (meth)acrylate polymer (B), from 0.05 to 20 parts by weight of initiating polymerization of the composition (C) containing partially oxidized tribution (c1) and x-ray contrast medium, provided that the total amount of components (A), (b) and (C) is 100 weight parts of the polymer (A) composed of polymer particles of many kinds, namely, the polymer (B) is a mixture of polymers, which comprises polymer particles (b1) having srednevekovoi molecular weight of 30×104up to 60×104and the specific surface area of from 1.5 to 4.5 (m2/g), polymer particles (b2) having srednevekovoi molecular weight of from 5×104up to 20×104and the specific surface area of from 0.51 to 1.2 (m2/g), and polymer particles (b3) having srednevekovoi molecular weight of from 5×104up to 20×104and the specific surface area of from 0.1 to 0.5 (m2/g), and contains polymer particles (b1) in an amount of from 0 to 98 wt.% and polymer particles (b2) and polymer particles (b3) in a total amount of not less than 2 in the S.% relative to the total weight of the polymer particles (b1), (b2) and (b3), provided that the total number of polymer particles (b1), (b2) and (b3) is 100 wt.%.

2. Composition for the reconstruction of hard tissue under item 1, where initiating the polymerization of the composition (C) contains an aprotic solvent (C2'), having a boiling point of from 30°C to 150°C, in the amount of 30-80 weight parts per 100 weight parts of boron compound (c1).

3. Composition for the reconstruction of hard tissue under item 1, where initiating the polymerization of the composition (C) contains an aprotic solvent (C2'), having a boiling point of from 50°C to 120°C, in the amount of 5-40 weight parts and the alcohol (C3) having a boiling point of from 60°C to 180°C, in an amount of from 0.2 to 5 weight parts per 100 weight parts of boron compound (c1).

4. Composition for the reconstruction of hard tissue according to any one of paragraphs.1-3, having a viscosity of from 0.4 to 2000000 SP within 30 seconds after mixing of components (A), (b) and (C).

5. Composition for the reconstruction of hard tissue according to any one of paragraphs.1-4, further comprising a polymerization inhibitor (D).

6. Composition for the reconstruction of hard tissue according to any one of paragraphs.1-5, where the concentration of the polymerization inhibitor (D) is in the range from 10 to 5000 ppm, relative to component (A).

7. Composition for the reconstruction of hard tissue under item 5 or 6, where the polymerization inhibitor (D) is at least the one substance, selected from hydroquinone, dibutylamino, simple nanometrology ether of hydroquinone, 2,6-di-tert-butylphenol, 2,6-di-tert-butyl-p-cresol, catechin, pyragollole, benzoquinone, 2-hydroxybenzophenone, p-methoxyphenol, t-butylcatechol, butylhydroxyanisole, butylhydroxytoluene and t-butylhydroquinone.

8. Composition for the reconstruction of hard tissue according to any one of paragraphs.1-7, further comprising an absorber of ultraviolet radiation.

9. Composition for the reconstruction of hard tissue according to any one of paragraphs.1-8, further comprising at least one substance selected from a plasticizer and softener.

10. Composition for the reconstruction of hard tissue according to any one of paragraphs.1-9, further comprising at least one substance selected from: anti-infective agents, antibiotics, antibacterial additives, antiviral agents, analgesics, combination analgesics, means reducing appetite, deworming drugs, anti-arthritis means, anti-asthma drugs, anticonvulsants, antidepressants, antidiuretic funds, Antidiarrhoeal funds, antihistamines, anti-inflammatory drugs, drugs against migraine, antiemetics, anti-tumor drugs, anti-parkinsonism, antipruritic drugs, neuroleptics, araponga is their preparations, antispasmodic funds, anticholinergics, sympathomimetic funds, cardiovascular drugs, antiarrhythmic drugs, antihypertensive drugs, diuretics, vasodilators, immunosuppressants, muscle relaxants, parasympatholytics drugs, stimulants, sedatives, tranquilizers, cholinergic funds, chemotherapeutic drugs, radiopharmaceuticals, medium, inducing the growth of bone tissue, heparin neutralizers, procoagulants, hemostatic means, xanthine derivatives, hormones, natural proteins or proteins synthesized by genetic engineering methods, polysaccharides, glycoproteins, lipoproteins, oligonucleotides, antibodies, antigens, vasopressin, and analogues of vasopressin, epinephrine, selectin, promoting coagulation toxins, inhibitors of factor activation of plasminogen activators of platelets, synthetic peptides having hemostatic action and fragrances such as orange oil, grapefruit oil, lemon oil, lime oil, clove oil, Wintergreen oil, peppermint oil, rectified peppermint, banana distillate, cucumber distillate, honey distillate, rose water, menthol, anethole, alkylsalicylate, benzaldehyde, MSG, ethyl is aniline, thymol and vanillin.

11. Composition for the reconstruction of hard tissue according to any one of paragraphs.1-9, which has a viscosity 80,000,000 JV within 540 seconds after mixing of components (A), (b) and (C).

12. Set for the reconstruction of hard tissue, with sections that are placed contained in the above composition for the reconstruction of hard tissue under item 1 components of the alkyl methacrylate (A), seamless (meth)acrylate polymer (b) and containing partially oxidized tributive initiate polymerization of the composition (C), in the form of two or more separate groups in arbitrary combination.

13. Set for the reconstruction of hard tissue by p. 12 having such a structure, in which the alkyl methacrylate (A), unstitched methacrylate polymer (B) and initiate polymerization of the composition (C) each placed separately, and the first monomer (A) is mixed with initiate polymerization of the composition (C) containing an organoboron compound, and then mixed with the polymer (B).

14. Set for the reconstruction of hard tissue, with sections in which the components of the alkyl methacrylate (A), unstitched methacrylate polymer (B) initiating polymerization of the composition (C) containing an organoboron compound, and the polymerization inhibitor (D), contained in the above composition for the reconstruction of hard tissue on p. 6, placed in the form of two or more of the Department is lnyh sets in arbitrary combination.

15. Set for the reconstruction of hard tissue on p. 14 having such a structure, in which a mixture of alkyl methacrylate (a) and the polymerization inhibitor (D), unstitched methacrylate polymer (b) and initiate polymerization of the composition (C), each independently placed separately, and first with a mixture of methacrylate (a) and the polymerization inhibitor (D) is mixed with initiate polymerization of the composition (C) containing an organoboron compound, and then mixed with the polymer (B).

16. Set for the reconstruction of hard tissue according to any one of paragraphs.12-15, comprising a device which is used to apply the composition to recover a solid fabric, which is obtained by mixing the components (A), (b) and (C), or composition for the reconstruction of hard tissue, which is obtained by mixing the components (A), (B), (C) and (D), the damaged part or region.

17. Set for the reconstruction of hard tissue on p. 16, where the device represents at least one device selected from a swab, brush, fiber ball, wipes, sponge ball or a piece of sponge.

18. Set for the reconstruction of hard tissue according to any one of paragraphs.12-17, optionally containing aqueous solution for pre-treatment, containing 1-15% wt. citric acid and 1-5 wt.% iron chloride (III).



 

Same patents:

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine and can be used for collection of organism's secretions. Device for collection of organism's secretions contains collection packet and adhesive pad for fixation to skin, and sad pad contains protective layer, first layer and second layer of hydrocolloidal adhesive substance, where second layer of hydrocolloidal adhesive substance, at least, partly is located between first layer of hydrocolloidal adhesive substance and protective layer. First and second layers of adhesive substance consist of continuous and discontinuous phase. Discontinuous phase of first layer of adhesive substance contains pectin, carboxymethylcellulose, gelatin, guar gum and potato starch, continuous phase of first layer of adhesive substance contains polyisobutylene, styrol block-copolymer, butyl rubber and tackifier. Discontinuous phase of second layer of adhesive substance contains carboxymethylcellulose, gelatin and guar gum, and continuous phase of second layer of adhesive substance contains polyisobutylene and styrol block-copolymer.

EFFECT: invention improves indices of tack and adhesiveness of first layer, which makes it possible to prevent passage of liquid, secreted fro body orifice through adhesive construction with preservation of low risk of irritation of skin around patient's body orifice.

11 cl, 3 dwg, 3 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to biocompatible polyisocyanate macromer or mixture of macromers for application as glue or sealant for internal application, represented by formula: , where f equals two or more; a in the range from 1 to 5 and R1 represents , where d is in the range from 0 to 5 and c can be in the range from 1 to 100; R2 represents , where R3 represents linear or branched residue of water-soluble polymer, which forms ester bonds with R4 and urethane bonds with R1, when a equals one or more; and R4 represents linear or branched organic residue, which contains two or more carboxylate terminal groups, and x gives the number of repeating R4 and is in the range 2≤x≤6. Also described are biocompatible elastic gel, obtained by polymerisation of said macromer, composition, applicable for medicine, and method of internal wound closing.

EFFECT: creation of glue or sealant for internal application, preserving ability for manipulations and smoothing, which fills internal sinuses and empty spaces, penetrates and tightly fits cavities and pores of tissue before hardening or setting, and is biologically decomposable.

9 cl, 3 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: present invention refers to medicine, and describes a medically applicable formulation containing macromer with terminal diisocyanate groups or a mixture thereof, and oxidised cellulose. This formulation is used as an adhesive or sealer for internal application.

EFFECT: use of the described formulation improves the polymer adhesion to the substrate when excessive free water in the operation place limits the effectiveness of the adhesive.

1 cl, 2 ex, 4 dwg

FIELD: medicine.

SUBSTANCE: invention refers to medicine. What is described is a medical semi-synthetic adhesive bioimplant of new generation of biopolymer nanocomposites in the form of semi-synthetic polymer matrix containing a base in the form of low-molecular polyisobutylene, an excipient in the form of collapan, a binding agent in the form of castor air-oil mist lubrication; in order to improve setting of the microporous adhesive sandwich, a repetitively-pulsed laser scalpel (CO2 laser) is used intraoperatively. An upper layer hardener is a polymer adhesive strip with polyacrylamide hydrogel placed in a polymer bath.

EFFECT: medical semi-synthetic adhesive bioimplant has high adhesion characteristics.

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medical equipment and may be used in producing adhesive elements for colo-, ileo- and urostomy bags and urine collection bags. The composition contains, wt %: acrylate copolymer 10-20, polyisobutylene 15-35, castor oil 10-20, hydrocolloids 20-30, and a target additive 0.1-30.

EFFECT: invention aims at preparing the adhesive polymeric composition having improved adhesion to polyolefines and natural latex, and also has a therapeutic and preventive action on skin, causes no irritations and erythemas.

4 cl, 1 tbl, 5 ex

FIELD: invention relates to medicine.

SUBSTANCE: method of agglutination of biological tissues is described herein; the method lies in smearing of the bio-degradable glue on the tissue; the glue containing liquid-hardened isocyanate-functional component is produced by interacting of: (a) the multifunctional isocyanate component and (b) multifunctional component with active hydrogen groups which includes at least 30% of the total mass of the multifunctional component with active hydrogen groups, multifunctional reagent with active hydrogen groups having the equivalent mass of less than 100; the relation of the R active hydrogen groups to the isocyanate groups can be less than 1.0.

EFFECT: agglutination of the biological tissues ensures good cosmetic result.

32 cl, 14 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: declared invention concerns hydrogel compositions useful as a dressing material or protective agent, and for application of a wide range of active substances in relation to the skin and tissues of mucosas, such as mouth, including tooth bleaches. The faza-parted, film-forming composition containing an admixture is offered: (a) the first polymer bulking up in water, and the specified polymer is not dissolved in water at pH less than approximately 5.5, or water-soluble polymer; (b) an admixture of hydrophylic polymer and additional low-molecular polymer, capable to formation of hydrogen communications with hydrophylic polymer; (c) the second polymer bulking up in water, and the specified polymer we will not dissolve in water at all value pH; and (d) unessential active substance, in a dissolvent or in an admixture of dissolvents where the composition is exposed to separation of phases at hydration.

EFFECT: treatment of a disease state of various surfaces of a body (teeth, fingernails, skin, mucosas etc).

44 cl, 7 ex

FIELD: medicine.

SUBSTANCE: adhesive contains mixed isocyanate-pattern molecules derived from molecule reaction with number of isocyanate functional groups with the complex precursor molecules including end functional groups, chosen from the group consisting of hydroxyl group, primary amides and secondary amides. Preferably, functional groups are hydroxyl. Complex precursor molecules are biologically compatible. Precursors with number of molecule amides with number of isocyanate functional groups are biologically compatible as well. Mixed molecules preferably has average isocyanate functional groups as at least, 2.1 and, more preferably, as at least, 2.5. Mixed molecules derive mixed cross-link polymers when contacting to organism tissues with water added. Cross-link polymer framework with is biologically compatible and biologically decomposable. Cross-link polymer framework is decomposed to products including molecules and precursors with number of functional amides.

EFFECT: improved adhesive and agglutination method.

20 cl, 4 dwg, 10 ex

FIELD: medicine.

SUBSTANCE: invention describes a glue composition contacting skin, with improved original and lasting adhesion properties, water absorption and light permeability, which can be obtained by a melt extrusion. The compositions can be applied in wound dressing.

EFFECT: improved composition.

97 cl

Antimicrobial gels // 2535013

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to medicine, particularly to aspects covering antimicrobial compositions, and described antimicrobial compositions, antimicrobial silicone gel based on the above antimicrobial composition, a wound dressing and methods for preparing them. Among other things, the antimicrobial compositions contain at least one alkenyl- and/or alkynyl-substituted polysiloxane, at least one polysiloxane containing silicone-linked hydrogen atoms, and at least one hydroxylation catalyst, at least one hydrophilic ingredient, at least one silver salt.

EFFECT: invention can be used for preparing a drug preparation to be used in treating burns, scars, bacterial infections, viral infections and/or mycotic infections.

19 cl, 5 dwg, 8 ex, 6 tbl

FIELD: medicine.

SUBSTANCE: what is described is a non-woven fabric consisting of several layers and comprises spot-glued carrier with polyamide nanofibres containing at least one antimicrobial substance, and a protecting coat. The polyamide nanofibres are made of polyamide and can be fixed on the carrier by means of a liquid adhesive. Non-woven fibre fabrics of the density of 15 to 90 g/m2 are used as the carrier of the nanofibres and protecting coat: polypropylene, polyester, cellulose-polyester, cellulose or paper. The polyamine nanofibres contain at least one antimicrobial substance in an amount of 0.4 to 35% of nanofibre weight among: guanidines, metal nanoparticles, stabilised silver salts, quaternary ammonium compound salts.

EFFECT: material possesses antimicrobial activity, high air permeability, and fracture resistance.

9 cl, 2 dwg, 5 ex

FIELD: medicine.

SUBSTANCE: what is described is hydrogel composition containing sodium acrylate, a linking agent, biologically active substances, polyvinyl pyrrolidone, glycerol, propanediol, water, a catalyst agent and a radical polymerisation indicator in the following proportions, wt %: sodium acrylate 2.0-10.0, catalyst agent 0.045-0.48, linking agent 0.195-0.21, radical polymerisation indicator 0.045-0.06, glycerol 4.5-7.5, propanediol 3.0-10.5, biologically active substances 0-1.5, polyvinyl pyrrolidone 0.3-1.5, water - the rest. What is described is a surgical dressing containing a carrier with the hydrogel composition applied thereon.

EFFECT: higher efficacy of the hydrogel composition and surgical dressing thereof, lower labour intensity of the method for preparing the above composition.

10 cl, 1 tbl, 2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to the field of obtaining and production of filtering materials for purification of air of industrial premises based on polymer fibres, possessing antibiotic properties. Synthesis of a polymer on a filtering material in low-temperature glow discharge plasma in adamantane vapours is performed. First, a chamber with the filtering material is vacuumed, argon is supplied and gas discharge purification of material is carried out. After purification the chamber is re-vacuumed and vapours of adamantane are input with further ignition of the glow discharge to obtain a thin coating on the material surface.

EFFECT: invention makes it possible to render antibiotic (antifungal) properties to the surface of the filtering material.

1 ex

FIELD: medicine.

SUBSTANCE: dressing represents a knitted mesh fabric coated with a composition of a biocompatible film-forming polymer of polyvinyl pyrrylidone and drug preparations: iodine, novociane, carboxymethyl cellulose sodium salt, of the following formulation (mg/cm2): iodine 0.0282±20%; polyvinyl pyrrylidone (Mr 20000) 1.2±20%; novociane 0.426±20%; carboxymethyl cellulose sodium salt 1.6-1.9.

EFFECT: using the wipe provides antimicrobial, antiseptic, disinfecting, antifungal and antiprotozoal action ensured by the fact that a polyvinyl pyrrylidone matrix retains iodine in the wipe and promotes its release on the skin.

FIELD: medicine.

SUBSTANCE: agent contains chitosan salt 75-95 wt % of polydisperse powders of chitosan hydrochloride, hydrobromide, formate, acetate, succinate, citrate, glycolate or lactate and polyhexamethylene guanidine hydrochloride 4-20 wt %. The chitosan salt and polyhexamethylene guanidine hydrochloride are covalently cross-linked by a polyfunctional compound 1-5 wt % of glycidyl ethers. The chitosan salt is specified with an average particle size of 0.2÷2.0 mm, degree of chitosan deacetylation 0.75÷0.95, and molecular weight 10÷500 kDa. The above polyfunctional compound of glycidyl ethers is presented by a diglycidyl ether of butandiol, di- or triethylene glycol or propylene glycol, oligoethylene oxide, as well as triglycidyl ethers of glycerol or trimethylol propane.

EFFECT: method possesses high blood sorption capacity, rapid hemostasis time and high antimicrobial activity.

3 cl, 2 tbl, 12 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to chemical-pharmaceutical industry and medical equipment and may be used in preparing multifunctional biological active structures for the fixation of dressings and objects. The fixation device consists of a paper carrier made of cellulose and viscous fibres impregnated with a special preparation, dried; with its one side of the prepared carrier coated with an adhesive and with its other side coated with a primer and an adhesive.

EFFECT: improved drape effect, enhancement, easier and faster usage.

6 cl, 1 tbl, 2 ex

Wound dressing ii // 2508127

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, more specifically to a sterile wound dressing having a bearing surface and a non-absorbent elastomeric layer contacting the wound; an elastomeric matrix comprises a synthetic three-unit elastomer, preferentially a polystyrene and polyolefin copolymer (SEPS, SEBS, SEEPS, etc.), or a mixture thereof; the total content of the polymer makes less than 3.2 wt %, particularly 3.0 wt % or less, preferentially 2.6 wt % or less, and plasticised by a non-polar oil and/or vaseline.

EFFECT: wound dressing provides better tissue compatibility.

12 cl, 1 tbl, 3 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine. What is described is a superabsorbent polymer composite containing superabsorbent polymers and cellulose nanofibrils having a diameter of 100 nm or less. The composite may be presented in the form of either particles, or foam. There are also described methods for preparing the composite and absorbent products containing the superabsorbent polymer composite.

EFFECT: cellulose nanofibrils improve the gel strength of the superabsorbent polymer.

23 cl, 6 dwg, 6 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, more specifically to a textile material for making dressings or absorbent tissues to be used for the infection protection of maxillofacial postoperative wounds. What is described is a multilayer material which is presented in the form of a needled non-woven 4÷25 mm thick with an area density 200÷1000 g/m. Both outside layers are formed of a viscose fibre, and at least one inside layer consists of a polypropylene and/or polyester fibre, with the external layer contacting the wound is processed with an antimicrobial and/or therapeutic preparation.

EFFECT: enabling both treatment and protection of the wound against the external environment and mechanical effect, and exudate absorption and transport.

9 cl, 1 dwg, 13 ex

FIELD: medicine.

SUBSTANCE: what is described is a coating in the form of a film which contains the following ingredients, wt %: low-molecular edible chitosan 5.3-5.7, glycerol 2.2-2.8, ceruloplasmin 0.06-0.08, L-asparaginic acid 0.04-0.06, a solvent with pH 5-7 - the rest. What is described is a method for preparing the coating consisting in the fact that a chitosan weigh is diluted in the solvent at 1000 mg of the weigh to 15 ml of the solvent, mixed and placed in a thermostat at a temperature of 37-42°C for 1-2 hours. The mixture is added with ceruloplasmin diluted in the solvent at 1:10 to form a homogenous hydrogel. L-asparaginic acid is diluted in the solvent pre-heated to 37-40°C and added to the mixture to provide pH of the mixture 5-7. A plasticising agent in the form of glycerol is added in the amount of 2.2-2.8% of total volume of the prepared biomass The prepared biomass is placed into containers to form a uniform layer of the coating 3-5 mm high and to form a film by drying the biomass for 18-24 hours in the thermostat at a temperature of 37-40°C.

EFFECT: wound coating provides the highest clinical effect.

6 cl, 6 dwg, 2 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine. What is described is using active ingredients as exemplified by GML (Glycerol Monolaurate) on a fibrous absorbent structure, such as viscose fibre, used for tampons production, in the very low concentrations enables maintaining effectiveness on the inhibition of synthesis of a toxic shock syndrome toxin 1 (TSST-1) produced by S.aureus, without evident microorganism elimination for the purpose of achieving the desired reduction of the toxin concentration and avoiding undesired impurities.

EFFECT: achieving the desired reduction of the toxin concentration and avoiding undesired impurities.

16 cl, 6 tbl, 3 ex

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