CS272350B1 - Surface bioactive vitreous crystalline material - Google Patents

Abstract

Surface-bioactive glass-crystalline particularly suitable for bone tooth replacement and artificial roots; contains 20 to 35% silica SiO 2, 4 30 to 45% calcium oxide CaO; 2 to 5% MgO, 10 to 10% 18% phosphorous oxide P 2 O 5; 0.1 to 0.3% fluorine F and other zirconia oxides ZrO? and yttrium oxide YgO3 in an amount of 8 and / or alumina Al 2 O 3 in an amount of 0.4 to 10% by weight.

Description

The present invention relates to a surface-bioactive glass-crystalline material, particularly suitable for bone replacement in the human body or for artificial tooth roots, based on silica SiO _2, calcium CaO and phosphorus Ρ ₂ θ5 *

Many materials are known for bone replacement, in particular from the group of metallic materials, plastic polymeric substances, ceramic corundum or zirconium materials and their composites.

All groups of materials used for bone replacements are constantly the subject of intensive research in order to achieve such biological, mechanical and chemical properties that they are as close as possible to the properties of the replaced tissue. The applicability of individual materials for implantation into a living organism depends on their properties, especially tissue biocompatibility, enzymatic and hydrolytic stability, chemical, physical, mechanical and other properties.

The biocompatibility of each implant is determined primarily by the type of chemical; physical and biological interactions between host tissue and the implant. The ss organism tries to isolate every foreign body from the surrounding tissue, creates a demarcating fibrous sheath around it and tries to eliminate it from the body. The wall thickness of the sheath around the implant is considered critical for assessing the degree of tissue compatibility of the implants. The thin wall of the housing is characterized by good compatibility of the material, a strong signal a high degree of rejection. An obvious requirement for compatible substances is that they must not have a cytotoxic effect, cause tissue necrosis and inflammatory reactions.

The formation of a more or less thick fibrous sheath is characteristic of all the above-mentioned materials, which brings considerable difficulties in fixing the implants in the body during surgical practice.

Another group of known materials are surface bioactive materials, for example bioD active glass Bioglass CL.L.BENCH. Proceedings of the 10th International Congress on Glass. Kyoto, Japan, July 1974 Ceramic Society of Oapan, Tokyo, 1974, N _o . 9. p. 30). U. This type of bioactive glass undergoes chemical bonding between the implant and the bone tissue without the formation of a fibrous sheath, so that anchoring of these implants in the host tissue offers completely new possibilities of application. Surface bioactive glasses based on soda-lime glasses with the addition of phosphorus oxide P ₂ 0g, for example with a composition of 45% by weight of silica SiO ₂ , 25.5% by weight, calcium oxide CaO, 24.5% by weight, sodium oxide Na ₂ 0 and 6 % by weight of phosphorus pentoxide ^ρ 2θ5 ' ^{in the} environment, in vitro or in' vivo, first by leaching sodium ions they form a surface film enriched in silica SiO2, on the outside of which a phosphate-calcium coating is formed, initially amorphous, which It changes to a polycrystalline layer of apatite agglomerates, which can incorporate organic components such as collagen, into 6 weeks. This layer is essential in physicochemical processes that allow the bond between the glass surface during implantation into the human body and the newly formed bone tissue. An equally important function of the formed surface layers is to suppress further dissolution of the glass and thus to ensure the desired stability of the implant during long-term application. However, despite their high bioactivity, these materials have low mechanical properties and are brittle, so that their application possibilities are significantly limited.

Surfactant rock crystalline materials are also known, for example CERAVITAL ^R CH.BROMER. K.DEU · SHER, B.BLENKE, E.PFEIL and V.STRUNZ, Sci. Ceram. 9 (1977) 219) or Glass ceramics A / W based on oxides of silica SiO ₂ , calcium CaO, phosphorus P ₂ 0 _g CT.KOKUBO, S.ITO, M.SHIGEMATSU, S.SAKKA and YAMAMURO, 3. Mater. Sci. 20 (1985) 2001). These bioactive glass-ceramic materials show relatively better mechanical properties, but still do not reach the desired values, in particular flexural strength and fracture toughness, compared to bioinsert materials such as corundum ceramics or metals. Another disadvantage is the limited possibility of control, prediction and control, bioactivity of these materials.

It is known from in vitro and in vivo experiments that the formation of a strong bond between a surfactant bioactive material and living bone tissue depends on the mutual rate of cheΜ.

CS 272 350 Bl ² mechanical processes; occurring on the surface of the bioactive material, as described above, and on the rate of new bone formation. If these processes take place at substantially different rates, so that the reactivity of the biologically active material is not able to monitor the formation of new bone tissue, the bond between the implant and the bone tissue is very weak and intermittent sheath intervening is highly likely. On the other hand, high bioactivity can cause the killing of living cells in the body and leads to an overall undesirable effect. In addition, each living organism responds specifically and individually, so that the optimal level of bioactivity will be different for the different sites in the human body where the implant is inserted, and will further depend on the patient's age and general condition. These conditions must be respected if we want to achieve an optimal result in terms of biocompatibility and at the same time good mechanical properties. Therefore, it is necessary to be able to control and even better predict the bioactive behavior of a glass-crystalline implant depending on its chemical and phase composition.

The above problem is solved by the surface bioactive glass crystalline material according to the invention, the essence of which consists in the fact that it contains silica XiOg in the amount of 20 to 35%, calcium oxide CaO in the amount of 30 to 45%, magnesium oxide MgO in the amount of 2 to 5% , phosphorus pentoxide P ₂ 0 ₅ in an amount of 10 to 18%, fluorine F in an amount of 0 ^,! 1 to 0.3%

a. Further, zirconia ZrO ₂ and yttrium Y ₂ O ₃ in an amount of 8 to 40% by weight, and / or alumina AlgOg in an amount of 0.4 to 10% by weight. In order to comply with the desired surface bioactive properties of the glass crystalline material, it is advantageous if no more than 0.3% by weight of sodium oxide Na ₂ O, at most 0.3% by weight of potassium oxide K ₂ O is introduced into the resulting glass crystalline material as impurities. and a maximum of 0.05% by weight of iron oxide Fe ₂ 0g.

The main advantage of this surface-bioactive glass-crystalline material, suitable for the implantation of bone replacements or tooth roots in the human body, is that its surface bioactivity can be controlled on the basis of its chemical composition.

According to results of a series of preliminary experiments and _how: a .zřejmé the examples below, bioactivity glassy crystalline material is essentially determined by the composition and structure of the residual glassy phase. The speed and character of chemical processes on the surface of bioactive glass-crystalline material in the given range of composition, which results in the formation of connections between implant and living bone tissue, are given by the open structure of the residual glass phase of glass-talc material, which can be qualitatively affected by 0 ° oxygens and O “unbridged oxides” in the glass structure of the residual glass phase. This balance can be expressed by the relation

0 ° + O ² ** 2 07

2 ·· ^J where O denotes free oxygen ions. • ii.

For the first approximation, the openness of the glass structure can be expressed by the parameters Y and X, where the mean number of bridging oxygen 0 ° a.

Y »2Z - 2R ·

X - 2R - Z · where Z is the mean number of all oxygens per polymer, i.e. the mean coordination number of the glass-forming cation, ’and R is the ratio of the total number of oxygen to the total number of glass-forming cations in the glass. The larger the value of Y, the more firmly and compactly it is connected to the spatial network. Conversely, with a smaller value of Y, the structural connection of the network is looser, with larger cavities in

2+ spaces of the network and easier mobility of modifiers of magnesium Mg and calcium ions 2+ *

Ca, which is reflected in the properties of glass and its bioactive ability.

• P ·

CS 272 350 Bl

The practical calculation of the parameters Y and X is shown in the following examples of compositions 1 and 3 according to the table.

The table shows the molar composition of the residual glass phase for the glass crystalline material in Example 3;

silica SiOg calcium oxide CaO 43,15% 3.90% magnesium oxide MgO 31,55% phosphorus pentoxide 2.34% alumina AlgOg 19.04%

From this molar composition of the residual glass phase, the R value can be determined as follows

as follows: component total. number of oxygen number of glass-forming cations silica SiOg 86.30 43.15 calcium oxide CaO. 3; 90 - magnesium oxide MgO 31.55 - phosphorus oxide PgOg 11, ‘70 4.68 alumina AlgOg 57.12 30, O8

190.57 85.91 of which R - 190.57: 85.91 «2.2182« ^ tcparameter X = 2R - Z π 4; 4365 - 4 = 0.4365

-parameter Y = 2Z - 2R and 8.000 - 4.4365 »3.5635

The average number of bridge oxygens 0 ° per tetrahedron is thus Y 3.50 and is therefore a very stable glass, in the structure of which on average more than three corners of each tetrahedra are common. Oak has been shown experimentally, this glassy crystalline material is inert and does not show bioactive properties,

The molar composition of the residual glass phase for the glass crystalline material of Example 1 is as follows according to the table:

silica SiOg calcium oxide CaO 47,92% 16.64% magnesium oxide MgO 30,46% phosphorus oxide PgO _g 3.75% alumina AlgOg 1.18%

Of which calculation R: component total. number of oxygen number of glass-forming cations

silica SiOg 95.84 47.92 calcium oxide CaO 16.64 - magnesium oxide MgO 30.46 - phosphorus oxide PgOg 18.75 7.50 alumina AlgOg 3.54 2.36

165.23 57.78

Of which R - 165,23: 57,78> 2,8596 parameter X - 2R - Z 5, '7183 - 4 = 1,7183 parameter Y «2Z - 2R« 8,0000 - 5,7183 - 2,2817

Thus, the mean number of bridging oxygen 0 ° is 2.28, indicating a high bioactive ability of the glass crystalline material, as confirmed by in vitro and in vivo experiments.

It is clear that the bipactivity of the glass-crystalline material in the defined composition can be controlled by the Y parameter of the residual glass phase, with the material showing a high bioactivity at an lowest recommended values of Y = 1.8 to 2.0 and an increasing value of 272,350 B the bioactivity is key, so that at Y = 3.5 ja it is bioinert. Another advantage of the bioactive material of the invention is that the bioactive glass crystalline material with controlled bioactivity comprises polycrystalline zirconia Zr0 ₂ and yttrium oxide ^and / ^no bo AlgOg alumina, which also enables the controlled bioactivity agent may also achieve a high mechanical strength and fracture toughness.

The practical embodiment of the invention is further described in the four exemplary embodiments given in the table. ·

Example 1 '

The melts of Exemplary Compositions 1, 2, 3 listed in the table were prepared by mixing the appropriate ratios of silica sand, calcium and magnesium carbonates, calcium phosphate, alumina and fluorspar and sealing in a platinum crucible in an electric furnace at 1550 ° C. Compositions 1, 2, 3 contained, in addition to the components listed in the table, traces of sodium oxide Na ₂ O and iron oxide Fe ₂ 0 ₃ , which were introduced into the melt by impurities from the raw materials. To improve homogeneity, the melts were mixed during melting with platinum stirrers. After melting, the melts were poured between metal cylinders to form glasses of the desired composition. The chilled glass slides were crushed in a jaw crusher and then ground in an agate bowl with a pestle. The crumb sorting was performed on sieves. From the fraction with a particle size of less than 40 .mu.m, compacts were prepared by isostatic pressing at pressures of 80 and 150 MPa. Paraffin or water was used as a binder. The actual sintering and crystallization took place in an electric furnace according to a predetermined temperature program by continuous heating at a rate of 0.5 ° C / min with a time delay at temperatures of 750 to 800 ° C and 1,050 to 1,100 ° C. The obtained glass-crystalline materials were subjected to X-ray diffraction analysis and the crystalline phases and their mass proportions were determined, which are given in the table together with the determined composition of the residual glass-phase.

. Biocompatibility and bioactivity of glass-crystalline materials were tested on the one hand by implantation in experimental animals (dogs) and on the other hand by laboratory macrocontact and dynamic cytotoxicity test, carcinogenicity test and mutagenic activity tests using Amos taste. Tasty cytotoxicities have shown that the prepared materials are completely cytotolerant with a negative indication of carcinogenicity and mutagenic activity. Implants of french fries of glass-crystalline materials measuring 10x5x5 mm were performed in the tibia and form of the knee joints of experimental dogs of both sexes of indeterminate breed and weighing 12 _ + 2 kg.

Implants prepared from glass-crystalline materials of composition 1 were in all cases firmly attached to bone tissue without an intermediate fibrous layer two months after implantation. In most cases, the surface of the implants was even partially or completely overgrown with compact bone. Because the implanted chips cannot be removed from the bone without force, chunks of bone and 1x2x2 mm surface bioactive glassy crystalline material were cleaved with a chisel or the sample was cut with a diamond saw to access the bone-glassy crystalline material sites for more detailed electron study. microscope and electron microprobe, which again confirmed the formation of a tight immediate bond between the implant and the bone tissue. Implants of glassy crystalline material exhibiting a Y 3, 5 residual rock phase parameter at the same time since implantation were surrounded by a 0.5 to 1 mm wide fibrous sheath and could be removed from the bed without forceps, demonstrating that no tight bonds between the implant and the bone tissue.

The ability of mutually binding of the prepared glass-crystalline materials was tested on the aggregation of two pieces of glass-crystalline material with a defined contact area in a simulated human plasma solution. Two samples of glass-crystalline material, rollers with a diameter of about 10 mm and a height of 10 mm, were placed together with a ground surface and bound with nylon thread. They were then immersed in the prepared solution in a 100 ml polyethylene container. Samples were tempered at 37 ° C and taken for observation at time intervals. The bodies of composition 1 formed a joint after only 4 weeks. After 8 weeks, the joint was tight, so

CS 272 350 Bl could not be separated by hand strain. Under improvised loading, the joint was not broken even under a stress of about 10 MPa.

The reactivity and ability of the rock crystalline material to form a bond for compositions 1 (Y * 2.28), 2 (Y »2.82) and 3 (Y« 3.56) decreased with increasing Y value, again at Y 3.5 the joint was not formed even after 20 weeks, so that the test rollers of composition 3 could be separated in the hand after releasing the nylon threads.

Example 2

First, a mixture of silica sand, calcium and magnesium carbonates, calcium and magnesium phosphates, aluminum hydroxide and calcium fluoride was prepared, corresponding to an oxide amount of 22.42 g of silica SiOg, 30.2 g of calcium oxide CaO, 2.80 g of magnesium oxide MgO, 11.5 g of phosphorus pentoxide Pg0 ₅ ^{0.3 9} AlgOg alumina and 0.1 g of fluorine F. the mixture was melted in a platinum crucible at 1550 ° C to a homogeneous melt and cooled between metal rolls. The resulting glass flakes were crushed to a grain size of less than 15 .mu.m. To the glass powder thus prepared was added a mixture of 24 g of zirconia ZrOg with the addition of 2.04 g of yttrium oxide YgOg and 6.5 g of alumina AlgOg, which was previously heat-treated at elevated pressure at 1450 ° C for 3.5 hours. hours and ground to a powder with a grain size of less than 20 .mu.m.

The powders were mixed well and then sintered and crystallized at elevated pressure and a temperature of 1,100 to 1,150 ° C for 2 to 3 hours. The resulting material was subjected to X-ray diffraction analysis, the proportion of the individual crystalline phases was determined and the Y-parameter of the residual glass phase was determined as shown in the table, composition 4. and a mechanical flexural strength of about 400 to 500 MPa.

Table

Examples of the composition of glass crystalline materials.

2 3 4

Chemical weights of the composition

silica SiOg 33; 23 32.64 31.44 22.42 calcium oxide CaO 44.71 43.92 42.30 30.20 magnesium oxide MgO 4.24 4.16 4; 01 2.80 phosphorus oxide PgOg 17.08 16, ‘78 16.16 11.50 alumina AlgOg 0.42 2/38 6.07 6.80 zirconia ZrOg - - · 24.00 yttrium oxide Y ₂ ° 3 - - - 2.04 fluor F 0.11 O; ll 0.11 0.10 Phase mass Ingredients apatite 30 35 35 20 wollastonite 45 35 35 20 whitlockit 5 0 0 0 zirconia Zr0 ₂ and yttria Yg0 ₃ 0 0 0 26 corundum 0 0 0 10 residual glass phase 20 20 20 7

CS 272 350 Bl

Chemical molar composition of the residual glass phase in percent

silica Si0 ₂ 47.92 46.24 43.15 33.36 calcium oxide CaO 16, ^μ 64 12.30 3.90 8.31 phosphorus pentoxide P ₂ 0 _g . 3, '75 3.58 2.34 12.66 magnesium oxide MgO 30, ‘46 30; '83 31.55 43.90 alumina Al ₂ 0 ₃ 1.18 7, '02 19.04 1.70 Parameter Y of the residual glass phase 2.28 2.82 3.56 1.96

BACKGROUND OF THE INVENTION

Claims (2)

1. Surface bioactive glass crystalline material; particularly suitable for bone replacements or artificial tooth roots, based on silica S10 ₂ , calcium CaO and phosphorus P ₂ ° 5 ', characterized in that; that it contains silica SiO ₂ in an amount of 20 to 35% by weight, calcium oxide CaO in an amount of 30 to 45% by weight. magnesium oxide MgO in an amount of 2 to 5 wt. phosphorus pentoxide P ₂ 0 ₅ in an amount of 10 to. 18% by weight . . fluorine F in an amount of 0.1 to 0.3% by weight. and furthermore zirconia ZrO ₂ and yttrium oxide Υ ₂ 0θ in an amount of 8 to 40% by weight, and / or alumina Al ₂ 0 ₃ in an amount of 0.4 to 10% by weight. 2. Surface bioactive rock crystalline material according to claim 1, characterized in that the content of iodine oxide Na ₂ O as well as potassium oxide K ₂ O does not exceed 0.3% by weight, and the content of ferric oxide FegOg does not exceed 0.05% by weight. .