The method of forming a bone implant

 

(57) Abstract:

The invention relates to the field of medicine and relates to a method of forming a bone implant, which can be used for plastic bone as in the treatment and prosthetics areas of bone affected by degeneration, when bone defects resulting from congenital or acquired diseases. The method of forming a bone implant is carried out in a homogeneous microheterogeneous environment in the synthesis of hydroxyapatite in aqueous solution at a temperature not exceeding 45oWith ions of calcium, phosphate and hydroxide on the collagen with the degree of dispersion of 1-100 μm-1when the potentiometric pH control 10,01,0 and concentration of reactive cations and anions. The material obtained upon completion of the synthesis centrifuged, washed with distilled water, dried at a temperature not exceeding 45oTo give it the desired shape required for operations on bone, Packed and sterilized. If necessary, the proposed material can optionally contain medicinal substances and drugs such as growth factors, immunosuppressive drugs, antibiotics, antiseptics, etc. in required concentration. Use the HN defect own newly formed bone tissue not only in the normal fractures, but slow accretion when splinter fractures, which leads to a considerable shortening rehabilitation patients. 3 C.p. f-crystals.

The invention relates to the field of medicine and relates to a method of forming a bone implant, which can be used for plastic bone as in the treatment and prosthetics areas of bone affected by degeneration, when bone defects resulting from congenital or acquired diseases.

At the present time to recover intraosseous defects in traumatology and orthopedics, surgical dentistry and maxillofacial surgery, dental implantology and Periodontology bone of auto - and allografts successfully replaced osteoplastic materials based on collagen and hydroxyapatite.

This requires the development of new materials and methods of its production, which would stimulate histogenesis from the patient.

A method of obtaining biocomposite materials for reconstructive surgery on the basis of "collagen-hydroxyapatite" by mixing an aqueous solution of collagen and hydroxyapatite powder, freeze the mixture in the will gorhaut freeze-drying. Products freeze-drying is pressed, structure in pairs glutaraldehyde or formaldehyde, then aerate, Packed and sterilized. If necessary, this material may contain any medicinal substance (EN 2174410 C2, publ. 10.10.2001).

The disadvantage of this method is the presence of the saturation point products freeze-drying pairs of aldehyde and does not have a uniform distribution of hydroxyapatite on the collagen.

The closest analogue to the claimed method of forming a bone implant is a method of bone formation on the basis of "collagen-hydroxyapatite", according to which the collagen matrix is placed in an aqueous solution containing calcium ions, phosphate and hydroxide, and the deposition of hydroxyapatite on collagen carried out under the action of electrophoresis. To prevent acidification of a solution containing calcium ions, it adds a hydroxide or carbonate of calcium, which prevents the dissolution of the main product - hydroxyapatite (EN 2174848 C1, publ. 20.10.2001).

The disadvantage of this method is the uneven distribution of microcrystalline hydroxyapatite on the collagen matrix, the use of electrochemical reactor, Trolis of calcium salt solution, which acid is formed, which is connected with the appearance in a solution of hydrogen ions.

Ca5(OH)(PO4)3+H+=5Ca2++3PO43-+H2O

Introduction to the solution an excess concentration of calcium hydroxide is not possible to accurately control the pH of the environment.

The task of the invention is to simplify the method of forming a bone implant in obtaining synthetic bone material that imitates the properties of natural bone tissue.

The technical result of the present invention is to create an implant that stimulates histogenesis patient and contributing adjustable bone resorption of the implant in the postoperative period. This is achieved by forming the material of the bone implant in a homogeneous microheterogeneous environment in the synthesis of hydroxyapatite in an aqueous solution of calcium ions, phosphate and hydroxide at a temperature not exceeding 45oWith the collagen. Microheterogeneous environment is provided by the degree of dispersion of 1-100 μm-1collagen and deposited it hydroxyapatite. The process is performed by potentiometric pH control 10,01,0 and concentration Rea the bath water, dried at a temperature not exceeding 45oWith, if necessary, make implantate some form composite after centrifugation pressed, packaged and sterilized.

If necessary, the proposed material can optionally contain medicinal substances and drugs such as growth factors, immunosuppressive drugs, antibiotics, antiseptics, etc. in required concentration.

Hydroxyapatite (HAP) - Ca5(HE)(RHO4)3- mineral substances by chemical composition, close to the main mineral component of bone tissue.

Collagen is a protein that is present in virtually every human tissue, extracellular forms the skeleton of tissues and actively influences the repair processes of damaged connective tissue, speeding up the healing process. In this invention can be any biologically compatible, collagen, for example, pharmaceutical - VFS 42.

Antibiotics are specific chemical substances produced by microorganisms and capable in small quantities to provide a selective toxic effect on pathogens. Antibiotics are used for inactivation of pathogenic mikroorganizmov necrobiology nature, possess anti-inflammatory action.

Depending on the chosen course of treatment, we offer bone implant may further comprise an antibiotic (e.g. gentamicin, lincomycin, and so on) or antiseptics (dioxidine, furatsilin and so on).

The invention is illustrated by examples of specific performance.

Example 1. To obtain a collagen matrix take native collagen, it is dispersed in an aqueous solution in a ratio of water to the collagen by weight of 1: 20, respectively. Then the reactor is filled with buffer solution with a pH 10,01,0 with dispersed therein collagen. The concentration of collagen is 5% by weight of water. Then with constant speed injected from one side of the reactor an aqueous solution containing calcium ions CA2+and on the other hand is an aqueous solution containing phosphate ions RHO43-and hydroxide HE-. The salt content of the component in the solution corresponds to the stoichiometric ratio reacts components. In the reactor continuously ensures uniform distribution of the reactants and products of the synthesis of the collagen (e.g., mixing). As a result, the synthesis of hydroxyapatite occurs in one the of ollagen and deposited it hydroxyapatite (collagen-Apatite composite). When this reaction occurs:

5Ca2+3PO43-+OH-=Ca5(OH)(PO4)3.

The resulting hydroxyapatite uniformly deposited on dispergirovannom collagen. The resulting collagen-Apatite composite upon completion of the synthesis centrifuged to separate the liquid containing the products of the synthesis reaction, washed with distilled water, dried at a temperature not exceeding 45oC. the material is Then packaged and sterilized by gamma radiation.

This method allows you to get a sample of the bone implant, stimulating histogenesis the patient, contributing to the regulation of bone resorption of the implant in the postoperative period.

Example 2. The method of forming bone implanta carried out in accordance with example 1. Adding antibiotic or antiseptic is carried out in a solution of dispersed collagen before mixing with hydroxyapatite.

Osteoconductivity, i.e. the effect of gradual replacement of the area of the defect own bone tissue was confirmed experimentally. With this purpose, the experimental male outbred rats shaped defect of the femur about 1 cm, then the area of the defect imposed obtained is after surgery, animals were taken from the experiment and performed histological examination of the injured area of the site. Histological studies have shown that 15 days after surgery, the bone implant weevils, border trepanned holes faintly traced, at the micro level was observed structure is almost identical to the structure of the normal femur.

At 1 month after surgery, the border trephination bone was not observed, the bone defect was not determined.

Prolonged action entered in the developed implant medicinal substances was confirmed microbiologically. Standard substrate with a nutrient medium and bacterial flora (Staphylococcus aureus and Escherichia coli) were applied to the implant with antibiotic. The expiration date of the drug was considered the time when the activity of the drug was less than 50%. The activity of the implant with antibiotic was expressed by a time delay bacterial growth. The study showed that antimicrobial activity Imperata remained within 3-7 days, while the antimicrobial activity of control solution of the antibiotic remained no more than 3-4 hours.

Example 3. Patient D., born in 1961 received multiple comminuted fractures of the mandible. When surgical intervention OS is wt.%. After a month radiographically in the area of the joints defined bone. After 4.5 months after surgery radiographically in the area of injury is defined monolithic bone.

Thus, clinical application of implant obtained by the proposed method provides a stimulating processes of substitution zone defect own newly formed bone tissue not only in the normal fractures, but slow accretion when splinter fracture, which leads to a considerable shortening rehabilitation patients.

1. The method of forming a bone implant comprising a dispersion of collagen in aqueous solution, the synthesis of hydroxyapatite by his deposition on collagen in microheterogeneous environment of an aqueous solution of calcium ions, phosphate and hydroxide when the potentiometric pH control 10,01,0 and reacting ions, when the degree of dispersion of 1-100 μm-1composite of collagen and besieged it hydroxyapatite, after which the resulting composite centrifuged, dried at a temperature not exceeding 45oWith and sterilized.

2. The method according to p. 1, characterized in that an aqueous solution of dispersed collagen impose additional medicinal substance is TBE medicinal substances used antibiotics, and/or growth factor, and/or immunosuppressive drugs, and/or antiseptics.

4. The method according to PP.1-3, characterized in that the composite after centrifugation give a desired shape, packaged and sterilized.

 

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