Calcium phosphate biomaterials
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to medicine. What is described is a biomaterial on the basis of calcium phosphate, preferentially on the basis of hydroxyapatite, or on the basis of a material containing hydroxyapatite, such as diphase calcium phosphates and calcium phosphate cements, and using it for making an implant or for positioning prosthesis for the purpose of osteoanagenesis.
EFFECT: biomaterial provides the excellent properties of biological compatibility and fast osteoneogenesis.
17 cl, 4 dwg, 1 tbl
The present invention relates to new biomaterials based on calcium phosphate, preferably hydroxyapatite, or on the basis of material containing hydroxyapatite, such as biphasic calcium phosphate and calcium phosphate cements, the method of its production and its use for obtaining an implant or for the installation of the prosthesis to ensure regeneration of bone tissue.
Recovery of bone lost, mainly due to injuries and, in more rare cases, tumors, represents one of the biggest difficulties faced by orthopaedic surgeons. Defects of small size, from "pronounced" false joint (defect consolidation of the fracture, where the likely loss of substance) to bone loss by length of 5-6 cm, most often represent objects autologous transplantation cancellous or cortical-cancellous bone taken from the iliac crest (the gold standard). Defects of large size (≥ 6 cm) require significantly more serious surgical operations like transfer of vascularized bone tissue or procedures Muscle. When the available quantity of autologous bone tissue is limited, bone consolidation random in nature, and such techniques are of different type are often the cause of postoperative complications by m the STU selection of transplant.
Various biomaterials that are available in clinical practice, theoretically allowing you to bypass the disadvantages of autologous transplant. Unfortunately, none of them compare with bone graft on the results and does not restore the substances lost in large numbers.
The most studied in the present materials is associated with biomaterials strains of mesenchymal cells obtained from bone marrow after a few weeks of breeding and cultivation of cells in vitro. This approach is time-consuming and costly, which limits the clinical results.
It is known that coagulated blood promotes the restoration of bone. L. Okazaki et al., Clin. Oral Impl. Res., 16, 2005, 236-243 described implants based powder demineralized bone or coagulated blood. In WO 02/068010 described composite material based on bone marrow, and this material contains implantable, biocompatible and porous matrix and coagulated material, such as coagulate bone marrow, blood, plasma.
Such materials representing the result of the combination of the substrate and optional coagulated blood, up to the present time used in maxillofacial surgery, where problems of consolidation of the bones are less significant, and little used or the e used when restoring a diaphyseal bone.
The methods of making such implants are required to take the blood from the donor, often representing a recipient of the implant, and then to carry out the stage of manipulation with the substrate (demineralized bone, synthetic polymer or ceramics), in particular the stage of mixing with the blood that is a source of contamination of the biomaterial. In addition, such methods are difficult to obtain homogeneous biomaterial.
Thus, there is a need for a method of producing an implantable biomaterial based on a synthetic substrate, which can be easily obtained and has a stable and homogeneous properties, and this method should provide excellent properties in relation to biological compatibility and rapid recovery of the quality of bone tissue without the need to resort to the stages of cultivation or selection.
The present invention eliminates the disadvantages of the prior art and provides bone of excellent quality in terms of hardness and vascularization. Furthermore, the method of obtaining such a biomaterial is a simple, easy to implement, does not require repeated surgical intervention in the patient's body and is not expensive compared with the methods predshestvuyuschei what about the level of technology.
Hydroxyapatite is a member of many materials for repair of bones. In this application, the hydroxyapatite may be used individually or in mixture with other components, such as, for example, in the case of biphasic calcium phosphate or calcium phosphate cements.
Biphasic calcium phosphate, BCP is used in many cases of medical and dental practices. Biphasic calcium phosphate as a material for restoration of bone was first described Nery et al., J. Calls. 1992, Sept., 63(9):729-35. BCP is a mixture of hydroxyapatite (HA) Ca10(PO4)6(OH)2and beta-forms of tricalcium phosphate Ca3(PO4)2(β-TCP). Its biological activity and bioresorbability can be adjusted by changing the content of hydroxyapatite and β-TCP, included in its composition.
In the US 2005/0226939 described method of producing nanoparticles of hydroxyapatite, and in this way apply the mixed composition based on calcium ions and phosphate ions and processing of microwave heating. The conditions described in this document do not provide for the formation of hydroxyapatite or BCP, impregnated with a solution of calcium chloride.
Biomaterials-based BCP have the advantage that, compared with other synthetic biomaterials they favor osteogenesis.
BCP was the object of a lot of olenych research: Lerouxel et al., Biomaterials, 2006, Sept., 27(26):4566-72, 18, 287-294; O. Malard et al., J. Biomed. Mater. Res., 46(1), 1999, 103; Mankani M.H. et al., Biotechnology and Bioengineering, 72(1), 2001, 96-107. Various authors carried out studies on the influence of particle size of BCP. On Mankani M.H. et al. the method includes mixing particles of HA/TCP with cells and then with fibrinogen and thrombin, restored in the solution of CaCl2. But the solution of CaCl2is more concentrated than the solution used in the present invention, and molar-mass ratio CaCl2/BCP exceeds the ratio used in the biomaterials of the present invention.
Trojani C. et al., Biomaterials, 27, 2006, 3256-3264 showed that a good osteoinductive could be achieved by implantation of a composite material "BCP/hydrogel Si-hydroxypropylmethylcellulose", to which were added cells in the bone marrow, in the case of BCP particles sorted in the range from 40 to 80 μm. However, such methods require the implementation stage of selection of bone marrow cells and their cultivation.
In WO 2006/015275 described method, promoting regeneration of bone tissue, and this method comprises a composition consisting of a substrate material based on calcium phosphate, plasma with a high content of platelets, calcium and activator receptor PAR, other than thrombin. But the concentration of CaCl2in such compositions is that the Oh high, he will act as an anticoagulant when used in the conditions of the present invention.
Both components of the BCP, i.e. HA and β-TCP are two main types of calcium phosphate used in osteobiol and dentistry. They have excellent biological compatibility, it is considered that their combination shows better biological activity and, therefore, greater efficiency, than HA or β-TCP used separately. In practice, the two components (HA and β-TCP) are in BCP synergistic effect.
Hydroxyapatite, after implantation in vivo, due to its chemical structure may facilitate the formation on its surface polishmaster with non-stoichiometric ratio of calcium phosphate Apatite (the so-called "biological Apatite") due to epitaxial growth. This layer of biological Apatite, which is very close to crystals of bone matrix, could promote cell adhesion and activity.
β-TCP, with a substantially higher solubility than the HA supports the saturation for calcium and phosphate in biological fluids surrounding the implant of the BCP. This feature allows you to maintain the phenomenon of precipitation of biological Apatite phase HA. In addition, this phase is much more Rezo is biswamoy, than HA, which gives the possibility to regulate the resorbable implant, by varying the ratio of HA/β-TCP.
These chemical phenomena have been shown in vitro (J.M. Bouler, G. Daculsi, Key Engineering Materials, 2001, 192-195 (in Russian):119-122; S. Yamada et al., Biomaterials 1997, 18:1037-41; S. Yamada et al., J. Biomed. Mater. Res., 1997, 37:346-52) and in vivo (Daculsi G. et al., J. Biomed. Mater. Res. 1989, 23:883-94; G. Daculsi et al., Int. Rev. Cytol. 1997, 129-191). These mechanisms probably contribute the best clinical effectiveness of BCP compared with single-phase materials of HA or TCP (Nery E.B. et al., J. Calls. 1992, 63:729-35; Ellinger R.F. et al., Int. J Periodontics Restorative Dent. 1986, 6:22-33; Passuti N. et al., Clin. Orthop. Relat. Res. 1989, (248):169-76; Gouin F. et al., Rev. Chir. Orthop. Reparatrice Appar. Mot. 1995, 81:59-65; Ransford A.O. et al., J. Bone Joint Surg. Br. 1998, 80:13-8; R. Cavagna et al., J. Long-Term effect of Med. Impl. 1999, 9:403-412).
The present invention is based on the recognition that some calcium phosphates, in particular calcium phosphate apatites, such as hydroxyapatite, inhibit spontaneous coagulation of whole blood in the case when they are in contact. Indeed, it was found that HA and BCP containing HA, inhibits spontaneous coagulation of whole blood in the case when they are in contact. It was also found that when the pre-impregnated hydroxyapatite or BCP saline solution (which is an aqueous NaCl solution according to instructions on the use of these biomaterials blood preveden which I then in contact with them, not coagulates.
Experimental conditions that allowed to install anticoagulant properties of the substrate material, described in detail in the experimental part.
The first object of the present invention is a method for implantable biomaterial containing a substrate based on at least calcium phosphate, such as hydroxyapatite or a mixture of hydroxyapatite and at least one other material, and this method includes at least one stage of impregnation of the substrate with at least one coagulant.
Under the substrate based on calcium phosphates understand the material containing at least one component of a type of calcium phosphate Apatite selected from hydroxyapatite, fluorapatite, polyamidine with non-stoichiometric ratio of Apatite (ANSPS), as well as their mixtures with other calcium phosphate biomaterials. These substrates can be composed of hydroxyapatite, BCP, ANSPS and Apatite calcium phosphate cements.
Saturated thus the substrate is then implanted at the place, which must be filled in the bone defect. This implantation of the substrate causes the coagulation of blood, which comes in contact with the biomaterial or penetrates into the biomaterial in situ. In tests carried out with BCP, it was found that the BCP, combined with coagulated blood, ensure which ensures good osteogenesis and leads to the formation of bone tissue is very acceptable quality in a very simple way in comparison with the methods of the prior art. Without impregnation BCP solution of coagulant osteogenesis occurs.
In one embodiment of the present invention the substrate on the basis of calcium phosphate, preferably hydroxyapatite or a mixture of hydroxyapatite and other material, is implanted in place, which should be filled in the bone defect, and then impregnate her at the place of implantation of the coagulant solution.
The substrate used in the present invention, preferably is a substrate on the basis of hydroxyapatite, fluorapatite, polyamidine with non-stoichiometric ratio of Apatite (ANSP) or mixtures of such compounds with at least one other material, such as tricalcium phosphate in α - and β-form (Ca3(PO4)2), dihydrate dicalcium phosphate (CaHPO4·2H2O), anhydrous dicalcium phosphate (CaHPO4), monocalcium phosphate monohydrate (CA(HPO4)2·H2O), tetracalcium (CA(PO4)2O) and ostskanirovat (Ca8H2(PO4)6). The substrate is predominantly represents the substrate on the basis of hydroxyapatite or HRV, preferably it represents the substrate on the basis of HRV.
The substrate and, in particular, Apatite or HRV, which can be used according to the present invention may be in any form: as a monolithic body, and the form does not necessarily sorted granules.
HRV, which can be used according to the present invention is a high temperature Frit. When HRV represents granules, crushed him and sorted, for example, by screening, depending on the selected diameter. HRV, which can be used according to the present invention mainly contains hydroxyapatite and β-tricalcium phosphate with a mass ratio of HA/β-TCP in the range from 5/95 to 95/5, preferably from 30/70 to 80/20 and preferably from 40/60 to 60/40.
Preferably it is of a porous substrate, in particular HRV, with pore sizes in the range from 50 nm to 1000 μm, preferably from 500 nm to 100 μm and more preferably from 1 to 50 microns.
If the substrate is, in particular HRV used in the present invention is a granule, its particle size is preferably in the range from 40 to 500 μm, preferably from 40 to 400 μm, more preferably from 40 to 300 μm and preferably from 80 to 200 microns.
Pellets or powder of HRV can be obtained by methods described Bouler et al., J. Biomed. Mater. Res., 1996, 32, 603-609; Bouler et al., J. Biomed. Mater. Res., 2000, 51, 680-684; Obadia et al., J. Biomed. Mater. Res., 2006, 80 (), 32-42.
HRV can be purchased from the company GRAFTYS SARL (AIX-EN-Provence).
Hydroxyapatite, which can be used according to the present invention, preferably represents the edge of the s. It can be purchased from the company GRAFTYS SARL.
More preferably the present invention relates to a biomaterial containing a substrate on the basis of calcium phosphate impregnated with a solution of at least one coagulant, representing a derivative of calcium, and the substrate is selected from hydroxyapatite and HRV, and the coagulant is an aqueous solution with a concentration in the range from 1 to 50 mmol/l, and the ratio between the solution of the coagulant and or HRV ranges from 0.5 to 5 vol./about. of coagulant solution relative to the volume or HRV.
The present invention preferably relates to a biomaterial containing a substrate on the basis of calcium phosphate impregnated with a solution of at least one coagulant, representing a derivative of calcium, and the substrate is selected from hydroxyapatite and HRV, and the coagulant, representing a derivative of calcium, contains a ratio in the range from 2.5 to 60 mmol of calcium per gram or HRV and preferably from 5 to 40 mmol of calcium per gram or HRV.
The coagulant is a coagulant on the basis of calcium, such as biologically compatible salt of calcium, such as, for example, CaCl2Ca(NO3)2, Ca(AcOEt)2, CaSO4.
The coagulant is preferably a coagulant on the basis of calcium and selected from biologists who Eski compatible salts of calcium and preferably from CaCl 2. To ensure impregnation of the substrate, in particular HA or BCP, coagulant, the latter is used in the form of an aqueous solution, preferably in aqueous solution with a concentration in the range from 1 to 50 mmol/l, preferably from 3 to 40 mmol/l and preferably from 5 to 20 mmol/L. these values are especially preferred when the coagulant is a salt of calcium and preferably CaCl2.
The ratio between the solution of the coagulant and the HA or the BCP used in the method according to the present invention is from 0.5 to 5 vol./about. of coagulant solution with respect to unit mass of HA or BCP and preferably from 1 to 3 and preferably equal to about 2.
One of the other variants of the present invention, the biomaterial is obtained directly before applying the substrate treatment on the basis of calcium phosphate directly before implantation.
Also may be provided for receipt of the biomaterial of the present invention in accordance with the following procedure: to impregnate the substrate based on calcium phosphates solution of coagulant, then dry or lyophilisate, then packaged in sterile conditions and stored substrate prior to its implantation.
Preferably the duration of the impregnation is from 1 minute to 1 hour, preferably from 1 to 30 minutes and preferably from 5 to 15 m the chickpeas.
According to another variant of the present invention, the biomaterial of the present invention can be obtained by soaking a substrate on the basis of calcium phosphate with a solution of a coagulant, then this biomaterial Packed in sterile conditions and stored in this form before implantation.
In one embodiment of the present invention can provide that the bio-substrate (based on the calcium phosphate) combined with the coagulant in the form of a powder. In particular, it is possible to mix the biomaterial, such as BCP or HA in the form of powder or granules, salt of calcium in the form of a powder of a solid body. Thus, the biomaterial can be stored prior to its application and impregnation extemporal aqueous solution, such as saline solution just before implantation during its application. The biomaterial may also be implanted in a dry form, without impregnation.
According to the present invention can be provided by introducing into the substrate, in particular in BCP, one or more possible additives, such as polymers, ceramic particles, compounds pharmaceutical purposes, biologically active substances, and the conditions of application of such materials are their biological compatibility and the absence of negative effects on the reaction of blood coagulation. If one of these additives turns out the t adverse effect on the coagulation of blood, this circumstance should be taken into account when determining the applicable amount of coagulant. For example, such additives or active substances can be used in the binding of the substrate, BCP or other material when mixing or impregnation or coating. Such additives are well known to experts in the art and are intended to modify the rheological properties of the biomaterial, its behaviour in vivo (hardness, resorption, osteogenesis) or actions against infections or inflammation (antibiotics, anti-infective, anti-inflammatory drugs).
Can also be provided by the introduction of a biomaterial according to the present invention one or more therapeutic compounds as compounds intended for the prevention or the treatment of pathologies selected from, for example, cancer, osteoporosis.
Can also be provided by the introduction into the biomaterial of the present invention adipose tissue or any other drug from tissues or cells taken from the patient who is the biomaterial, and such fatty tissue or such a drug previously suspended in the blood, plasma or saline solution.
In the biomaterial of the present invention it is also possible to introduce a natural or synthetic facto is s growth. Can also be provided by the presence of biomarkers or contrast agents, enabling visualization of resorption of the biomaterial and its changes in the body through medical equipment to obtain images.
According to the method according to the present invention a substrate, in particular HA or BCP, is placed in the cavity of a closed and sterile container. If the substrate is in the form of granules, it can, for example, be placed in the inner cavity of the syringe. The appropriate amount of coagulant is introduced into the container, for example by dialing into the syringe, in the case of using such a device.
In the case where the substrate, in particular HA or BCP, is a monolithic body, then it is placed in the appropriate container shapes and sizes.
In all cases the volume of the container provide in order to provide the introduction of the desired quantity of coagulant solution.
After closing the container contained in the substrate, in particular HA or BCP, and the coagulant can be mixed to ensure uniform impregnation of the biomaterial. But it can also be provided by passive substrate treatment coagulant.
After this stage, the biomaterial is:
- homogeneous liquid paste, if the substrate was used in the form of pellets;
- solid body, the cavity of which C is acted upon by the fluid, if the substrate was used in the form of a monolithic body.
In one embodiment of the present invention may be provided for implantation into a fillable space directly to the substrate material, if necessary, mixed with the coagulant in the form of a powder, followed by impregnation in situ as a coagulant solution, and in the case where the substrate is already mixed with the coagulant corresponding aqueous solution, such as saline. Can also be provided by implantation without impregnation in the case where the substrate is a dry mix with a coagulant, which is then soaked with blood from surrounding tissues.
Another object of the present invention is a biomaterial containing a substrate on the basis of calcium phosphate such as hydroxyapatite or BCP, impregnated with a solution of at least one previously described coagulant.
Based on the physical form of the substrate, the HA or the BCP, and the type of device used to produce the biomaterial of the present invention, the biomaterial can then be made through devices, more adapted to move in place, which should be filled in the bone defect, for example, by means of an instrument such as a spatula, or by means of a syringe, having a side opening adapted to rheological properties and particle size of the biomaterial of the present invention. The biomaterial may also be implanted directly in the form of a monolithic body. In this case, the biomaterial must be designed or executed so that its shape and dimensions corresponded to fill the space.
The present invention relates also to a method of filling the bone defect, and this method includes the earlier stage and, in addition, the phase space of the biomaterial in a place where there is a bone defect. In addition, this method may include the stages of dissection of tissue and suture.
Based on the size and configuration of the bone defect, filling the biomaterial of the present invention may be combined with a temporary fixation, allowing you to give the affected tissue mechanical strength required for the recovery time of the bones at the site of implantation of the biomaterial of the present invention.
Applicants found that the implantation of the biomaterial of the present invention would facilitate the formation of bone tissue in a short time (a few weeks), and this bone had a very good vascularization.
Another object of the present invention is a kit for implementing the method of the present invention, and this set includes a combination of the substrate on the basis of calcium phosphate is, such as hydroxyapatite or a mixture of hydroxyapatite and at least one other material, such as, for example, microporous BCP, coagulant, representing a derivative of calcium. The coagulant is preferably a biologically compatible salt of calcium, such as CaCl2.
The amount of coagulant expect to compensate for the anticoagulant effect of calcium phosphate, in particular hydroxyapatite, and facilitate coagulation of blood into the surrounding tissues.
This combination can be a set, which includes:
(a) a sterile device having a sterile internal cavity in which is placed a substrate, such as, for example, BCP or HA;
(b) a sterile container containing a coagulant.
Capacity (b) may be a part of the device (a) or a separate product, such as a test tube or vial, which can be selected coagulant to move into the internal cavity of the device (a), or a syringe, allowing you to enter a coagulant into the cavity, in which is placed the substrate.
The internal cavity of the device (a) has a size that allows you to enter a coagulant in an amount necessary for obtaining a biomaterial according to the present invention and other components of the mixture, such as, for example, of the active substance.
Device (a) mainly contains the e means, ensuring the application of the biomaterial in the area having the defect of the bone.
Such a device can be a syringe.
Can also be provided using a device such as the device described in WO 02/068010, which includes the tube, inside which holds the substrate, in particular BCP, which is injected coagulant and which may be provided with a piston for displacement of the biomaterial after its formation.
The biomaterial according to the present invention can be used to obtain a bone implant in the case of filling the fracture site, compensate loss of substance due to injury or destruction of the tumor, the defect resulting from a surgical operation, or to facilitate the installation of the prosthesis.
The biomaterial through surgical operations can be entered in the area, which must be filled in the bone defect. After dissection of the biomaterial is implanted, and the wound closed.
The biomaterial of the present invention may be combined with osteosynthesis with the purpose of providing temporary consolidation to stabilize the area having the defect of the bone.
The coating of the prosthesis by the biomaterial of the present invention favors the introduction of a living bone into the prosthesis or around it.
The biomaterial of the present invention can also be is used in vitro or ex vivo as a substrate for the production of bone tissue.
In practice, the cultivation of bone cells around the biomaterial allows you to produce bone tissue, which can then be implanted.
Another object of the present invention is the use of in vitro or ex vivo as described earlier biomaterial to receive a bone implant.
According to the present invention can be grown bone cells on the biomaterial of the present invention in a form appropriate configuration manufactured prosthesis. Cultivation of cells under such conditions allows to obtain biocompatible prosthesis of appropriate shapes and sizes.
Fig. 1A-1D. - Getting implants and surgical procedure
Fig. 2. - Graphical representation of the concentration of calcium in plasma is in contact with the biomaterials of calcium phosphate
Fig. 3A. - Photo of the product obtained by addition of calcium chloride to the BCP and HA before the addition of blood.
Fig. 3B. - Photo of the product obtained by the addition to the BCP solution of calcium chloride with increasing concentration.
Fig. 4. - Study of scanning electron microscopy implants obtained using whole blood taken without anticoagulant (A, C), and BCP microparticles (80-200 μm), and implants obtained by the traditional method (B, D). In implants, be obtained the use of calcium, noticeable lack of education fibrin mesh and blood clot around the granules (A, C). Arrow white color in Fig. C indicates a few red blood cells, deposited on the granules. The scale on the figures: A and B: 100 μm; C and D: 10 μm.
I - the Effect of BCP and HA coagulation
We are talking about extemporally procedure performed in the operating theatre. The procedure involves mixing in the cavity of a syringe made of polypropylene particles BCP and coagulant CaCl2. Implantation of such a biomaterial according to the place where there is a bone defect, favors coagulation around the biomaterial.
2. Materials and methods
2.1. Particles biphasic calcium phosphate
The biomaterial of the biphasic calcium phosphate (BCP) is composed of 60% hydroxyapatite (HA; Ca10(PO4)6(OH)2and 40% tricalcium phosphate (TCP; Ca3(PO4)2). The BCP particles sorted in the range from 40 to 200 μm, were supplied by GRAFTYS SARL (AIX-EN-Provence, France). Particles were sterilized by heating at 180°C for two hours.
2.2. Measurement of calcium concentration in mouse plasma
The concentration of calcium was measured in the plasma of C57BL/6 mice (Janvier, Le Genet-Saint-Isle, France). This plasma obtained from blood taken from the addition of heparin by centrifugation at 1800 g is for 15 minutes. Heparin was used as anticoagulant, do not change the concentration of calcium in plasma. The analysis was carried out for automatically operating the device Hitachi (Orleans, France).
2.3. Getting implants and surgical procedure
As shown in Fig. 1A-1D, use the syringe (1)with a cylindrical hollow body (2), in which moves a piston (3). With the end of the body (2), is not closed by the piston, the body of the syringe is closed filter cap (4). In case (2) of the syringe between the end face (5) of the piston and the filter cap (4) are granules (6) BCP (Fig. 1A). To use the kit has been sterilized. The end of a syringe equipped with a filter cap (4)placed in the container (7)filled with an aqueous solution (8) CaCl2with a concentration of 1%. The movement of the piston (3) back ensures the absorption of the solution (8) into the housing (2) of the syringe (1) (Fig. 1B). Kit left alone for 10 minutes to BCP particles becomes saturated, and then through a piston (3) the excess of the solution (8) CaCl2squeeze through the filter cap (4) (Fig. 1C). Filter cap (4) remove the filter (9) and the pressure on the piston (3) is applied granules (6) BCP impregnated with a solution of (8), at the place of operation (10) (Fig. 1D). Then place the implant close (stage not shown).
3.1. Effect of hydroxyapatite and TCP coagulation
50 mg of HA powder or powder DROMEDARY in a syringe with a capacity of 1 ml In each of the syringes containing HA or TCP were added to 100 µl of blood. The resulting mixture was placed on the rotor, which was able to maintain the powder in the blood in a state of suspension during the time of coagulation, i.e. within 10 minutes. In each experiment one syringe containing 100 µl of whole blood and aged, as well as other syringes, i.e. within 10 min, rotor, served as a positive control coagulation. After 10 minutes, the rotor is stopped, the syringes were removed, their ends cut off and a mixture of blood/powder" squeezed, pushing the plunger of the syringe. Noted the presence or absence of blood coagulation around the powder. Each experiment was repeated 3 times.
It was observed that in the presence of 50 mg HA and 100 µl of whole blood coagulation was ingibirovany. The blood was still liquid.
Supervisory experience: positive control coagulation. Note the presence of the clot and exudation of serum.
In the presence of 50 mg TCP+100 µl of blood was coagulation, it was expressed in the formation of the implant, in which the fibrin mesh supported the powder in suspension in a uniform manner.
The same experiment was carried out by adding calcium chloride to the syringe containing HA, before the introduction of blood: it was observed coagulation and formation of the implant.
3.2. The effect of BCP on coagulation
Applicants it was observed that blood (100 μl), vegetariana in the absence of an the of coagulant and immediately mixed with BCP particles (50 mg), not coagulates. This anticoagulant effect is eliminated by the addition of CaCl2(20 µl of 1%solution of CaCl2), which leads to the assumption that the capture BCP plasma calcium. This hypothesis was confirmed by the measurement of the concentration of calcium in plasma before and after contact with BCP. This purpose was obtained plasma from the blood of C57BL/6 mice, selected with the addition of heparin (an anticoagulant does not affect the plasma concentration of calcium). In the presence of BCP applicants was seen falling plasma concentration of calcium of 2.06 ± 0.06 mmol/l (normal value) to a 0.59 ± 0.07 mmol/L.
II - Effect of biomaterials based on calcium phosphates in plasma calcium concentration
Aliquots of 50 mg of BCP microparticles (60/40), aliquots of 50 mg HA or β-TCP were mixed with 50 μl of H2O or with 50 μl of a 2.5 mm solution of CaCl2·2H2O and dried overnight at 56°C. these samples were introduced into the wells of the microplate of 96 wells. In each of the wells was added 100 μl of plasma obtained from the blood of C57BL/6 mice, selected with the addition of heparin, i.e. anticoagulant, which does not affect the calcium content. After soaking for 15 minutes, the microplate was centrifuged for 2 minutes at 800 g, and the supernatant was collected to determine the concentration of calcium in plasma. Determination of calcium on Westlake, using the kit QuantiChrom Calcium Assay (CENTAUR, Brussels, Belgium) accordingly to the manufacturer's instructions. With this purpose, aliquots of 5 µl of the supernatant was mixed with 200 μl of a solution of phenolsulfonphthalein representing the dye, forming a stable complex of blue in the presence of free calcium ions. After soaking for 3 minutes is staining, the intensity of which is determined at 612 nm, is directly proportional to the calcium concentration in the sample. Each microplate was preparing a series of standards based on calcium concentrations 0-0,5-1-1,5-2-3-4-5 mm.
2. The results:
Applicants were installed (Fig. 2)that the BCP in the form of microparticles, and the HA powder, brought into contact with the plasma, induced a significant and meaningful reduction in the concentration of calcium. The drop in calcium concentration was comparable in the case of BCP and HA was not observed in the case of β-TCP. Based on the values obtained for the same plasma (1,960±0,044 mm), for a plasma in the presence of BCP (0,871±0,160 mm) and plasma in the presence of HA (0,840±0,121 mm) applicants assessed the capture of calcium value 0.125 mmol of calcium 50 mg BCP or HA.
Applicants also found that the addition of 50 μl of a 2.5 mm solution (or 0.125 mmol) to BCP or HA before the addition of plasma allows to restore normal plasma concentration of calcium (Fig. 2). This is the number of calcium chloride, added to β-TCP, is summed with the original amount of calcium in the plasma, which confirms the lack of capture of this biomaterial in such conditions.
At the same time applicants, it was observed that the capture of calcium was identical for the three specimens tested BCP with different particle size, i.e. for particles the size of 40-80, 80-200 and 200-500 microns.
In addition, applicants have obtained the same results in respect of compensation by the addition of calcium as in the case of extemporanea the addition of calcium chloride immediately before the addition of plasma, and in the case of pre-evaporation of this solution was in contact with the particles.
III - the Effect of addition of calcium on the anticoagulant properties of BCP and HA
To prove the existence of a causal link between inhibition of coagulation and decrease plasma calcium content induced by BCP and HA, applicants were carried out tests of coagulation aliquot of 50 mg of BCP microparticles (60/40) and 50 mg of HA powder after addition of 50 ál of 150 mm NaCl or 50 μl of a 2.5 mm solution of CaCl2·2H2O.
2. The results:
After addition of raw anticoagulant blood and keeping on the rotor for 15 minutes by the applicants was established (Fig. 3A)that the preliminary addition of calcium to the BCP and HA on which allows to restore the coagulation of blood in the presence of both of these biomaterials.
The results obtained prove that the anticoagulant effect of BCP and HA is associated with a decrease in plasma calcium concentration caused by both of these biomaterials, and the addition of calcium provides restoration of coagulation.
Applicants analyzed the response, the dose of calcium on the coagulation of blood, brought into contact with BCP (Fig. 3B). The biomaterial was obtained by adding 100 µl of whole blood, not supplemented with anticoagulant to 50 mg of BCP particles in the presence of a solution of CaCl2·2H2O, taken in a fixed volume of 50 ál and prepared with concentrations of 0.01% (0.68 mm) and 0.02% (1,36 mm) to 0.05% (3.4 mm) and 0.1% (6.8 mm) to 0.2% (13,6 mm) to 0.5% (34 mm) - 1% (68 mm) - 10% (680 mm), or the same volume of NaCl solution with a concentration of 150 mm. After soaking for 15 minutes on the rotor, the biomaterial was removed. Applicants found that at low concentrations, corresponding in this case, 0.01 and 0.02%of the added calcium is not provided recovery of coagulation. At concentrations in the range of from 0.05 to 0.5% was observed coagulation. In an unexpected way by the applicants, it was found that increasing the concentration of CaCl2·2H2O up to 1% and over again induced inhibition of coagulation (Fig. 3B and table. 1).
These tests allowed to determine the optimal concentration of calcium, providing blocking anticoagu antago effect BCP 60/40, and showed that there is a range of concentrations, the observance of which is very important.
IV. The study fibrin mesh, scanning electron microscopy
Anticoagulant effect of BCP visually estimated by the lack of cohesive gel implants during the previously described tests, corresponds to the molecular level inhibition of the formation of a fibrin mesh that forms the skeleton of the bunch. Applicants were carried out research on the presence of fibrin mesh by scanning electron microscopy. To this end, the implant was obtained by mixing 100 µl of blood, not supplemented with anticoagulant with 50 mg BCP or 50 mg BCP sustained in the presence of calcium and then dried. After incubation for 15 minutes on the rotor of the mixture were removed and immediately immersed in fixative of 1.6%solution of glutaraldehyde in phosphate buffer solution with a concentration of 0.1 M and pH=7. Then the samples were washed, obezvozhivani in ethanol solutions with increasing concentrations, was immersed for 5 minutes in hexamethyldisilazane (Sigma-Aldrich, L'isle d ABO-Shen, France) and dried at room temperature. After fixing on an aluminum substrate and a coating layer of gold-palladium for 4 minutes (Polaron, A5100, UK) carried out a study by scanning electron is on microscope (JEOL 6700F, Japan).
As can be seen in Fig. 4, in the case of BCP fibrin mesh (Fig. 4A, 4C) between BCP microparticles is not observed. The presence of multiple red blood cells, deposited on the granules, indicates a mixture of particles with blood. In contrast, in the presence of system BCP/calcium indicates the presence of a clot compressing particles, and the clot is rendered cells fibrin mesh and a very large number of red blood cells (Fig. 4B, 4D).
|The concentration of the solution CaCl2·2H2O added to a mixture of BCP and blood (in% and polyarnosti)||The number of mmol of calcium, brought to 50 μl of a solution of CaCl2·2H2O||Test coagulation mixture of 50 mg of BCP + 100 ál blood + 50 μl of a solution of CaCl2·2H2O (in liquid form or after drying)"|
|0,01% (0.68 mm)||0,034||-|
|1% (68 mm)||3,4||+/-|
|10% (680 mm)||34||-|
1. Biomaterial for bone tissue regeneration containing the substrate on the basis of calcium phosphate impregnated with a solution of at least one coagulant, representing a derivative of calcium, and under orca selected from hydroxyapatite and biphasic calcium phosphate (BCP), and the coagulant is an aqueous solution with a concentration in the range from 1 to 50 mmol/l, and the ratio between the solution of the coagulant and or HRV ranges from 0.5 to 5 vol./about. of coagulant solution relative to the volume or HRV.
2. The biomaterial according to claim 1, in which the coagulant, representing a derivative of calcium, contains a ratio in the range from 2.5 to 60 mmol of calcium per gram or HRV and preferably from 5 to 40 mmol of calcium per gram or HRV.
3. The biomaterial according to claim 1 or 2, in which the coagulant is a CaCl2.
4. The biomaterial according to claim 1 or 2, wherein the substrate is a monolithic body.
5. The biomaterial according to claim 1 or 2, in which the substrate is in the form of granules with a particle size preferably in the range from 40 to 500 μm, more preferably from 40 to 400 μm, even more preferably from 40 to 300 μm and preferably from 80 to 200 microns.
6. The biomaterial according to claim 1 or 2, additionally containing at least one additive selected from polymers, ceramic particles, compounds, pharmaceutical purpose, natural or synthetic growth factors, biomarkers, contrast agents, drugs from tissues or cells.
7. The biomaterial according to claim 1 or 2 for use as an implant in the method of filling the bone defect.
8. Combination to regen the promotion of bone biomaterial according to any one of claims 1 to 7 with osteosynthesis.
9. Set for regeneration of bone tissue to the method of obtaining the biomaterial according to any one of claims 1 to 7, and this set includes a combination of the substrate based ON or HRV with coagulant, representing a derivative of calcium in the form of an aqueous solution with a concentration in the range from 1 to 50 mm/l, and the ratio of the coagulant solution and ON or HRV ranges from 0.5 to 5 vol./about. of coagulant solution relative to the volume or HRV.
10. Set for regeneration of bone tissue to the method of obtaining the biomaterial according to any one of claims 1 to 7, and this set includes a combination of the substrate based ON or HRV with coagulant, representing a derivative of calcium in dry form and/or in the form of a powder, and the coagulant, representing a derivative of calcium, contains a ratio in the range from 2.5 to 60 mmol of calcium per gram or HRV.
11. The set of claim 10, in which the coagulant, representing a derivative of calcium, contains a ratio in the range from 5 to 40 mmol of calcium per gram or HRV.
12. The kit according to claim 9 or 10, in which the coagulant is a CaCl2.
13. The kit according to claim 9 or 10, which includes:
(a) a sterile device having a sterile internal cavity in which is placed the substrate;
(b) a sterile container containing a coagulant.
14. The kit according to claim 9 or 10, in the cat the rum device (a) includes tools, ensuring the application of the biomaterial in the area having the defect of the bone.
15. The kit according to claim 9 or 10, in which the device (a) is a syringe.
16. The application of the biomaterial according to any one of claims 1 to 7 in vitro or ex vivo as a substrate for the production of bone tissue.
17. The application of the biomaterial according to any one of claims 1 to 7 in vitro or ex vivo as a substrate for receiving a bone implant.
SUBSTANCE: invention relates to chemical-pharmaceutical industry and represents artificial dura mater, produced from electrospinning layers by technology of electorspinning, with electrospinning layer, consisting of, at least, hydrophobic electrospining layer, which is produced from one or several hydrophobic polymers, selected from polylatic acid and polycaprolactone.
EFFECT: invention ensures creation of artificial dura mater, which has good tissue compatibility, anti-adhesiveness and possibility of introducing medications, preventing cerebrospinal fluid outflow during regeneration of person's own dura mater.
30 cl, 7 ex, 11 dwg
SUBSTANCE: claimed invention relates to ophthalmological device, method of its obtaining. Device contains antimicrobial particles of metal salts, which have size less than approximately 200 nm, dispersed throughout polymer mass. Device ensures at least 0.5 log reduction of at least one of Pseudomonas aeruginosa and S.aureus, and opacity value constituting less than 100%, with 70 micron thickness, in comparison with CSI lens.
EFFECT: invention possesses high antibacterial activity 3 independent claims, 34 dependent claims of invention formula.
17 tbl, 46 ex, 5 dwg
SUBSTANCE: group of inventions refers to medicine, particularly to ophthalmology, namely: to antibacterial lenses containing metals, as well as to methods for producing them. The method for producing an antibacterial lens containing a metal salt involves the stages: (a) preparation of a hard lens by a salt precursor, as well as (b) preparation of the lens produced at the stage (a) by a disperse additive specified in a group consisting of polyvinylpyrrolidone, polyvinyl alcohol, glycerol and polyethylene oxide, and a metal-containing agent specified in a group consisting of silver tetrafluoroborate, silver sulphate, zinc acetate, zinc sulphate, copper acetate, copper sulphate, silver nitrate, manganese sulphide, zinc oxide, zinc sulphide, copper sulphide, copper phosphate, silver nitrate, silver sulphate, silver iodate, silver carbonate, silver phosphate, silver sulphide, silver chloride, silver chloride, silver bromide, silver iodide and silver oxide. The other method for producing involves the stages (a) of preparation of a hard lens by a metal-containing agent, and a disperse agent, (b) preparation of the lens prepared at the stage (a) by a salt precursor. The antibacterial lens containing the metal salt is produced by said methods.
EFFECT: group of inventions provides producing the lenses with a decreased degree of opacity.
16 cl, 1 tbl
SUBSTANCE: invention refers to medicine, namely to textile treatment for cardiovascular surgery. A method involves textile treatment with a composition containing gelatin and intermolecular cross-linking of gelatin by an aqueous solution of glutaric dialdehyde, an antibiotic and 0.9% sodium chloride in certain proportions.
EFFECT: method enables make textiles hermetic and antimicrobial, reduced postoperative chemotherapeutic load on the patient.
5 cl, 11 tbl, 11 ex
SUBSTANCE: invention relates to N-substituted monomers and polymers used in medical devices. Disclosed is a polymer meant for use in implantable medical devices, which contains a plurality of monomer repeating units containing an N-substituted amide of formula (I) where each of X1 and X2 is independently selected from Br and I; each y1 and y2 is independently equal to zero or an integer ranging from 1 to 4, and R1 is selected from substituted or unsubstituted, saturated or unsaturated, straight or branched aliphatic groups containing up to 48 carbon atoms, substituted or unsubstituted aromatic groups containing up to 48 carbon atoms, and substituted or unsubstituted araliphatic groups containing up to 48 carbon atoms, wherein the aliphatic parts are straight or branched and saturated or unsaturated, wherein R1 contains 2-8 heteroatoms selected from O, S and N, where two of the heteroatoms form an amide group of the polymer backbone chain which is an N-substituted C1-C6 alkyl group. Corresponding monomers and versions of use of the disclosed polymer in medicine are also disclosed.
EFFECT: disclosed polymers are characterised by low melt viscosity and can be easily processed without decomposition.
24 cl, 8 ex
SUBSTANCE: group of inventions relates to antibacterial lenses, containing metals and methods of their obtaining. Method of obtaining antibacterial lens, containing metal salt, is characterised by a) stage of processing hardened lens with solution, containing salt precursor and b) processing of lens, obtained at stage a) with solution, containing metal-containing agent, where molar ratio of said metal-containing agent in its solution constitutes from 0.6 to 10.0.
EFFECT: invention ensures obtaining antibacterial lens with low content of opacity/Ag, which makes possible its long application with transparency, sufficient for user to be able to see through the lens clearly.
10 cl, 1 tbl, 1 dwg, 4 ex
SUBSTANCE: group of inventions relates to field of medicine, in particular, to ophthalmology. Group of inventions relate to antibacterial lenses, which contain metals, and methods of there production. Antibacterial lens which contains metal salt, obtained by method (versions), which includes stages: (a) processing hardened lens by solution, which contains metal-containing preparation and efficient quantity of acid substance, where pH of claimed solution constitutes from 2 to 5; and (b) processing of lens from (a) stage with solution, containing, basically containing or consisting of salt precursor and efficient quantity of acid substance, where pH of said solution constitutes from 2 to 5.
EFFECT: group of inventions ensures obtaining contact lenses, which contain antibacterial medications of constant composition.
19 cl, 2 dwg, 2 ex
SUBSTANCE: invention refers to medicine. There are described medical implanted devices made of a polymer material and a separation agent wherein the device is a cast reservoir implant, while the separation agent has a molecular weight (M.w.) of min. 1000. The separation agent can be presented by a non-ionic surfactant, such as Bridge-35, polyoxyethylene (20) sorbitan trioleate, Tween 20, Tween 80, vitamin E TPGS, and a mixture of any two or more of them. The hydrated implants can have a surface area of approximately 500 mm2 or more.
EFFECT: used separation agents causes no undesired reactions with cartridge polymer and are safely introducible in a patient.
29 cl, 5 tbl, 3 ex
SUBSTANCE: invention refers to medicine, specifically to cardiovascular surgery and may be used for modification of synthetic implanted medical devices. What is described is a method for processing synthetic textile implanted medical devices involving coating the devices with hydrogel of natural biodegradable polymers wherein the natural biodegradable polymer is presented by polysaccharide chitosan or its derivatives (carboxymethykated sulphated chitosan) in a combination with polyester-poly-3-hydroxybutyrate. The coating is dried and transferred in the water-soluble state by thermal processing at 100°C.
EFFECT: method for processing synthetic textile implanted blood contact medical devices enables providing the devices with a complex of the required properties: higher thromboresistance and antimicrobial action, zero surgical porosity and prolonged drug release.
3 cl, 1 tbl, 5 ex
SUBSTANCE: invention relates to medicine. Described is membrane envelope of implanted dosing system, which is suitable for hypodermic application. Membrane envelope contains first half and second half, and both halves contain continuous locking edge and are made with possibility of connection to each other by means of lockable connection. Locking edges of halves contain, at least, one hollow and/or, at least, one projection, made as continuous or discontinuous, and membrane envelope is made with possibility of locking in such a way, that, at least, one projection and/or, at least, one hollow of second half became opposite to, at least, one hollow and/or, at least one projection of first half by means of locking connection.
EFFECT: membrane envelope is suitable for hypodermic application aimed at separation of active agent in constant quantity during increased time interval.
10 cl, 2 dwg, 1 ex
SUBSTANCE: producing method of monophasic nanocrystalline silicon-replaced hydroxyapatite involves synthesis of silicon-containing hydroxyapatite by means of a method for deposition from water solution of reagents containing orthophosphoric acid, calcium hydroxide and tetraethyl orthosilicate at pH of not less than 9 and molar ratio of Ca/P in the range of 2.0 to 2.5; sedimentation for completion of a phase formation process, extraction of deposit, drying and heat treatment of deposit; with that, synthesis is performed by adding 10-20% solution of orthophosphoric acid at the speed of 0.2-0.8 ml/min per litre of water solution of calcium hydroxide / tetraethyl orthosilicate composition prepared by means of 0.08-0.16% water solution of calcium hydroxide and design amount of tetraethyl orthosilicate to obtain a finished product with silicon replacement degree x equal to 1-2 and molar ratio of Ca/(P+Si), which is close to 1.67, and heat treatment is performed at the temperature of not lower than 300°C, but not higher than 400°C. Invention allows obtaining stoichiometric monophasic product of phases with average size of crystals of 9.95-12.53 nm, specific surface of 108.97-132.58 m2/g, and increased bioactivity, at the heating of which incidental phases do not occur.
EFFECT: improvement of characteristics.
4 dwg, 2 tbl, 8 ex
SUBSTANCE: invention relates to a method of producing canaphite, i.e. a hydrated disodium pyrophosphate of calcium (Na2CaP2O7*4H2O). The method involves feeding starting components: water, a crystalline hydrate of sodium pyrophosphate, calcium acetate or a crystalline hydrate of calcium nitrate, in molar ratio of the crystalline hydrate of sodium pyrophosphate to calcium acetate or crystalline hydrate of calcium nitrate of 0.98-1.02 and ratio of the mass of water to mass of the produced canaphite of 0.7-0.8. Said components then react while mixing intensely in a planetary mill at a rate of 5000-7000 rpm for 1-3 hours. The obtained product is then washed with water 4-6 times and disaggregated.
EFFECT: method enables to obtain single-phase canaphite powder with particle size in the range of 100-500 nm with high output of the end product.
1 tbl, 2 ex
SUBSTANCE: invention refers to porous microsphere granules with the adjusted particle size for bone tissue regeneration. The above microspheres have a size within the range of 1-1000 mcm, have through pores of the size of 1-100 mcm and total porosity 40-75%. The declared microsphere granules are prepared by granulation by electrospinning, and heat-treated. A mixture used to form the granules by electrospinning contains a mixture of magnesium orthophosphate and biological hydroxyapatite of bovine demineralised bones in ratio 0.5:1.0, as well as 1-3% sodium alginate in distilled water and a hardener representing saturated calcium chloride.
EFFECT: invention provides preparing the microsphere granules possessing biocompatibility, biodegradation, osteoinduction and osteoconduction properties and able to be substituted by the bone tissue.
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers medicine, namely to preparing biological hydroxyapatite. What is described is a method for preparing biological hydroxyapatite involving pre-cleaning of bones, grinding, dissolving of bone tissue in hydrochloric acid, hydroxyapatite precipitation using a precipitant, filtration, heat treatment and deposit grinding; bones are ground to a particle size of 2.5-5 cm; bone tissue is dissolved hydrochloric acid of the concentration of 0.5-2M; that is followed by separating a liquid fraction of the suspension by filtration with the filtered solution added with chitosan of the concentration of 1.5-2 wt % at constant mixing until completely dissolved. The hydroxyapatite precipitant is 3-5M sodium hydroxide or potassium hydroxide added at constant mixing to ensure pH 7.0-7.5 of the reaction mixture; the filtered precipitation is heat treated by calcination at temperature 830°C for at least 40 minutes
EFFECT: fine hydroxyapatite powder of the particle size of 5 nm having the composition of microelements being as close as possible to that of human bone tissue.
SUBSTANCE: invention relates to medicine, namely to method of obtaining biocompatible bone-substituting material; powder of biological hydroxyapatite with particle size not more than 40 mcm is obtained from cattle bones, powder of hydroxyapatite is mixed with magnesium phosphate powder with particle size not more than 40 mcm with their ratio 1.0:0.25, water suspension of 2-amino-5-guanidine valeric acid is added to obtained mixture of powders with their further mixing for 40-50 minutes and drying at 50-60°C. Obtained mixture is combined with liquid, containing chitosane solution in 3% water solution of succinic acid and 2% water solution of sodium alginate with their ratio 0.3:0.7, ratio between liquid and powder mixture being 1.0:0.5. Before application hardening agent 5-10% water solution of calcium chloride is added to obtained plastic mass with ratio 1.0:0.3.
EFFECT: obtained material has through pores 0,7-100 mcm, general porosity 50-85%, is biocompatible, biodegradable and contains conditions, which eliminate necessity of t bone tissue transplantation and reoperation.
2 cl, 1 ex
SUBSTANCE: invention relates to composite materials based on calcium phosphate ceramic with improved strength properties and can be used in filling bone defects in traumatology and orthopaedics, maxillofacial surgery and dental surgery. To obtain reinforced porous composite materials based on hydroxyapatite and tricalcium phosphate, a porous ceramic matrix of a calcium phosphate ceramic with the ratio Ca/P ranging from 1.5 to 1.67 is saturated with 1-5% solution of average molecular or high molecular chitosan in 8% acetic acid at residual pressure of 0.1 to 0.3 Pa and holding for 10 to 30 minutes, followed by drying at room temperature for 24 hours.
EFFECT: invention increases strength of the composite material 8-9-fold.
3 ex, 1 tbl
SUBSTANCE: group of inventions relates to three-dimensional matrix from monetite with structured porosity, method of claimed matrix synthesis and mould for its obtaining and application of monetite matrix for regeneration of bone structure. In its structure claimed monetite matrix has vertical cylindrical macropores with diameter from 350 to 650 mcm, which cross matrix in longitudinal direction from one end to another, and are located at from 0.4 mm to 0.6 mm distance from each other. Mould for obtaining claimed matrix is provided with uniformly allocated cogs with diameter 350-650 mcm, which are uniformly located at 0.4 - 0.6 mm distance from each other. Method of synthesis of monetite matrix includes stages of mixing basic calcium phosphates, acid calcium phosphates, pore-forming agent and setting retardant, and solidification by adding distillated water with formation of liquid phase, filling mould with said liquid phase, sterilisation of formed precursor material and its thermal transformation in monetite.
EFFECT: inventions are directed at obtaining matrix from bio-material monetite with predetermined porosity, which ensures possibility of neo-vascularisation and inoculation with cells and is bioactive, non-cytotoxic, non-mutagenic and hemo-compatible.
44 cl, 38 dwg, 11 ex
SUBSTANCE: invention refers to medicine, and may be used for facialmaxillary osseous prosthesis, as a drug delivery system and as a matrix for tissue engineering structures. Bruschite cement contains (wt %): β-tricalcium phosphate - 34.5-45, monocalcium phosphate monohydrate - 23-29.5, bioactive glass - 0.5-10, water-base tempering fluid 25-32.5. The bioactive glasses are strongly alkaline glasses as follows (wt %): SiO2-40-60, CaO-10-25, Na2O-22-35, P2O5-3-5, of insular, chain, ring or layer silica-oxygen motifs. The glasses are introduced in the amorphous or crystalline state at the granule dispersity 30 to 80 and 80 to 120 mcm.
EFFECT: allows adjusting the dig structure of the material, its mechanical properties, pH and solubility in the buffer solutions, as well as enables intensifying the regenerative processes in the injured osseous structures and reducing the length of treatment and recovery of the bone integrity.
8 cl, 8 ex
SUBSTANCE: method involves mixing phosphates, calcium and silicon compounds, milling and mechanochemical synthesis, wherein the starting components used are disubstituted anhydrous calcium phosphate, annealed calcium oxide and amorphous hydrated silicon oxide with water content of less than 0.5 mol, with specific surface area of 200-450 m2/g in amount of not more than 1.2 mol silicon per elementary cell of hydroxylapatite; mechanochemical solid-phase synthesis is carried out in high-energy planetary mills with drum rotation speed of 1200-1800 rpm for 12-30 minutes. Calcium oxide is annealed preferably at temperature of 900°C for 5 hours.
EFFECT: invention enables to obtain a powdered nanocrystalline single-phase product for 30 minutes of solid-phase mechanical activation.
2 cl, 1 tbl, 6 ex, 7 dwg
SUBSTANCE: invention refers to medicine and concerns composites for plastic reconstruction of the injured bone tissues. The composite is presented in the form of reaction-set mixed powders: tricalcium phosphate, containing hydroxyapatite particles ranging in size from 38 to 220 mcm. Fluid cement is presented by a solution of magnesium, potassium and/or sodium phosphates, phosphoric acid and water. The components are taken in certain proportions. In the process of the material setting, a solid frame with a uniform distribution of ceramic particles contributing to an increase in strength is formed.
EFFECT: high mechanical properties and availability of raw materials allows using the given material widely for closing the bone cavities.
1 tbl, 1 ex
SUBSTANCE: method involves applying hydroxyapatite collagen material plate so that plate size is selected to be by 5-8 mm greater than trepanation opening.
EFFECT: enhanced effectiveness in making plastic repair of maxillary sinus; excluded allergic responses.