DD248351A1 - Glass-ceramic bioactive material - Google Patents

Abstract

The subject of the invention is a glass-ceramic bioactive material of the CaO-P2O5-SiO2 type with apatite, wollastonite and cristobalite crystal phase for alloplastic bone replacement. The object of the invention is to further improve the chemical stability of ceramic-active bioactive material of the CaO-P2O5-SiO2 type with apatite and wollastonite crystal phase for alloplastic bone replacement, while maintaining known peak bioactivity and fracture mechanical behavior. Object of the invention is the change in the chemical composition and the Keramisierungsprozesses of glass-ceramic bioactive material CaO-P2O5-SiO2-type with apatite and wollastonite crystal phase for alloplastic bone replacement with regard to the creation of a direct connective tissue bone contact after implantation, improvement of hydrolytic resistance and a simultaneous formation of the structure in the mold, which produces good fracture-mechanical properties (high KIC values). The material according to the invention is characterized by a content (calculated on an oxide basis and in% by mass) 30 to 50 CaO, 2 to 20 P2O5, 27 to 53 SiO2, 0.1 to 4 Na2O, 0.1 to 0.5 K2O, 0.1 to 4 MgO, 0.1 to 5.5 Al2O3, 0.1 to 6 CaF2 and 0.1 to 7.5 ZrO2, the sum of CaF2 and ZrO2 being 1 to 10 mass% and the sum of Al 2 O 3 and ZrO 2 are 1 to 8% by mass. The manufacturing process of the material is shown in the description of the invention.

Description

Field of application of the invention

The invention relates to glass-ceramic bioactive material of CaO-P ₂ O ₅ -SiO ₂ -TyP with apatite, wollastonite and cristobalite crystal phase for the alloplastic bone substitute.

This material is characterized by improved chemical resistance as a result of the stabilization and structural alteration of the superficial Ca / P-rich layer with hydroxylapatite-like structure which was hitherto considered necessary for high bioactivity. Despite this stabilization of the Ca / P-rich layer formed in vivo in the course of the corrosion process, an equally good bioactivity is achieved, as was the case with the previously known solutions. At the same time, the corresponding additives cause a change in the crystallization behavior. By means of a method according to the invention for producing the glass-ceramic bioactive material, a microstructure is created which is characterized by the presence of apatite, wollastonite and cristobalite crystal phases. This structural structure has a positive effect on the fracture-mechanical behavior of the corresponding shaped bodies.

Characteristic of the known technical solutions

Heretofore, bioactive glass crystalline materials are essentially known from the following patent literature:

a) on the basis of apatite crystal phase DE-AS 2.326.1 OO

DE-AS 2,349,859 DE-OS 2,606,540

b) on the basis of apatite and mica crystal phases DE-OS 3,306,648

c) based on apatite and wollastonite crystal phase IP patent 57 / 191,252

In DE-AS 2,326,100 glass ceramic materials for prosthetic purposes with apatitic crystal phases through a range of chemical composition in the limits of (Ma .-%) 20-60SiO ₂ , 5-40P ₂ O ₆ , 2.7-20Na ₂ 0.04-20K ₂ O 2.9-30MgO, 5-40 CaO and 0.05-3 F, wherein the addition of fluoride or fluorine ion donating compounds according to the invention to an advantageous embodiment of the recrystallization process, in particular with respect to a improved nucleation tendency leads.

In DE-AS 2,349,859, glass ceramic materials with apatitic crystal phase are obtained within the range of the chemical composition claimed in DE-AS 2,326,100 by an additional ion exchange process in the near-surface layer of the material with improved mechanical properties {strength behavior). DE-OS 2,606,540 describes biocompatible glass ceramics for implantation with apatitic crystal phase with the addition of fluorides and rare earth oxides (yttrium or lanthanum oxides), wherein up to three isomorphic with the natural hydroxyapatite crystal phases, eg. B. of the type of fluorinated lanthanum Apatite be formed. The addition of the rare earth oxides is attributed to biocompatibility advantageous influencing effect.

The writings cited under a) take into account only one prior art, which is oriented exclusively on apatitic crystal phases and does not yet take into account the coexistence of further crystal phases for improving the strength, which offers the glass-ceramic molded body, in addition to the bioactivity, further advantageous properties, such as, for example, machinability under b) cited font.

In DE-OS 3,306,648, machinable bioactive glass-ceramics are proposed on the basis of apatite and mica crystals or on the basis of apatite, mica and anorthite crystals. Such glass-ceramics, which can be formed both by controlled cooling of the melt and by thermal aftertreatment, contain as starting materials (in% by mass) 19-52SiO ₂ , 12-23Al ₂ O ₃ , 5-15MgO, 9-30CaO, 4- 24P ₂ O ₅ , 0.5-7F "and 3-10R ₂ O, where R ₂ O is equal to the sum of 0-8Ma% Na ₂ O and 0-8Ma% K ₂ O. The advantageous property of machinability of these bioactive glass-ceramics (for example also during the operation) is diminished by the disadvantage of a remarkably high content of Al ₂ O 3 addition of more than 10 mass% By WIHSMANN et al. (Wiss. Journal of the Friedrich Schiller University) Jena , Math. Naturwiss Row 32 (1983), (553-569), it has become known that high levels of Al ₂ Oa in the course of prolonged in-vivo lifetimes lead to a separate Al-rich protective layer which limits bioactivity and to significantly lower levels Furthermore, it has been known that when using high levels attention must be paid to AI ₂ O 3, especially from a toxicological point of view, since even very small leaching can lead to damage, so that the physiological variance of the ion concentrations in the blood or body fluid must be strictly adhered to. (See: RICKENBACHER and SCHLATTER, Naturwiss 70 [1983], 303).

In the patent IP 57 / 191,252 an implant material prepared by sintering and subsequent crystallization is claimed, which contains crystalline phases of the type hydroxyapatite for biological coupling and wollastonite to increase the strength and in Ma .-% of 42 to 53CaO, 22 to 41 SiO ₂ , 10 to 27P ₂ O ₅ 1 to 7 MgO and smaller 10Li, Na, K, Sr, B, Al, Ti, Zr, Nb and Ta oxides and CaF ₂ consists. This proposed solution has the disadvantage that with this material only fracture mechanical properties (K _ic value of 0.79 MPa.m- ^1/2 ) properties can be achieved, which represent only a slight improvement over the values of the starting glasses (see KOKUBO , Lecture, International Congress of Glass, Hamburg, FRG, 1983). The reason for this could be considered to be the increased MgO content, since either the residual glass phase must take up the MgO fraction or else, which is likely in the case of a high MgO content, additional MgO-containing crystal phases are added. In addition, it is known that increased release of Mg ²⁺ ions from the implant material associated with high MgO levels adversely affects the mineralization process of the newly formed bone. Another disadvantage is the limited chemical resistance.

Finally, in the DD patent application WPC 03C / 255974/3, a glass-ceramic bioactive material of the CaO-P ₂ O ₅ -SiO ₂ type with apatite and wollastonite crystal phase proposed for the bone substitute, which is characterized by a content (from oxide base and in Ma calculated .-%) of 30-50CaO, 2 to 20 P ₂ O _5, 27-53SiO _2, 4,7 ₂ 0,0,2 Nn Na ₂ O and 0.95 MgO and 1-6CaF ₂ wherein the mass ratio CaO: P ₂ O _{5 is} between 2 and 20. This material is obtained by glass ceramic. It

- ύ- AtO ΟΌ I

a significant improvement of the fracture mechanical properties (K ^ value between 1.8 and 2.6 MPa m ^1/2 ) in combination with the chemical resistance of 1.4 to 2.6 ml 0.01 η HCl according to standard TGL 14809 achieved , According to the conventional principle, however, a further improvement of the chemical resistance does not make sense, since this automatically leads to a limitation of the bioactivity (the hydrolytic resistance and the bioactivity are characterized by a reciprocal course).

However, it would be advantageous to find a new solution for increasing hydrolytic stability which does not limit bioactivity and thus abolishes the existing dependence of the counteracting behavior between bioactivity and hydrolytic resistance.

Object of the invention

The aim of the invention is, in the case of glass-ceramic bioactive material of CaO-P ₂ O ₅ -SiO ₂ -Typ with apatite and wollastonite crystal phase, for alloplastic bone replacement, the chemical resistance, while maintaining the known peak values for the bioactivity and with respect to the fracture mechanical behavior, continue to improve.

The technical problem which is solved by the invention

The invention has for its object to change the chemical composition and the ceramization process of glass-ceramic bioactive material of CaO-P ₂ O ₅ -SiO ₂ -Typ with apatite and wollastonite crystal phase for the bone substitute so that the corrosion layer formed after implantation the surface of the implant is treated by the organism as endogenous hard tissue, ie leads to direct connective tissue free bone contact, this layer overall improves the hydrolytic resistance and at the same time in the molding body to a microstructure, the good fracture mechanical properties, characterized by high K | _C values, yields.

Features of the invention

A glass-ceramic bioactive material of CaO-P ₂ O ₅ -SiO ₂ -TyP with apatite, wollastonite and cristobalite crystal phase was found for the alloplastic bone substitute, in which a special reaction corrosion zone is formed in the course of the lying time in vivo, and which allows for a kind of microstructure including considerable cristobalite parts, which have good fracture mechanical properties, characterized by high K | _C values, lead. This material is characterized by being (calculated on an oxide basis)

30 to 50 Wt .-% CaO 2 to 20 Ma .-% P ₂ O ₅ 27 to 53 % By weight of SiO ₂ 0,1bis4 Ma .-%, preferably 0.1 to 3.5 Ma .-% Na ₂ O 0.1 to 0.5 Ma .-%, preferably 0.1 to 0.18 Ma .-% K ₂ O 0.1 to 4 Ma .-%, preferably 0.1 to 0.8 Wt .-% MgO 0.1 to 5.5 Ma .-% Al ₂ O ₃ 0.1 to 6 Ma .-% CaF ₂ 0.1 to 7.5 Ma .-% ZrO ₂

and

where the sum of CaF ₂ and ZrO _{2 is} 1 to 10% by mass and the sum of Al ₂ O ₃ and ZrO _{2 is} 1 to 8% by mass, and has the following property parameters:

Fracture Mechanical Properties:

Critical Stress Intensity Factor (K | _C ) between 1.6 and 2.6 MPn · m ^1/2

Hydrolytic resistance (according to standard TGL 14809:

0.15 to 0.85 ml 0.01 η HCl

Bioactivity (expressed as the size of the bone-implant interface in% after one year of laytime):

up to 80%

biocompatibility:

- no cytotoxic reactions in different cell cultures,

- Detectable inflammation-free ingrowth in the hard tissue.

There has also been found a process for producing the glass-ceramic bioactive material which comprises melting a mixture of the above-mentioned composition (calculated on the basis of oxide and calculated in terms of% by weight) into a glass,

- the molten glass deforms orfrittet and the molded or fritted glass

- a temperature-time program

Heating at a speed between 0.1 and 10K min ^-1 to a temperature between 850 ⁰ C and 1050 ° C and maintaining this temperature between 10 minutes and 48 hours and cooling at between 1 and 2OK min ^-1 lying speed to room temperature

subjects. , "

The material may be molded after melting, as will be the case when it is intended for use as an implant molding, or it may be fritted if it is to be used as a component for producing a bioactive composite (composite or coating). In each of these two cases, the material is advantageously subjected to a temperature-time program in order to convert the glassy products thus obtained into glass-crystalline ones. A further advantage of the bioactive glass-ceramics according to the invention is the process found for this transformation, since it is designed as a one-step program and, for the purpose of nucleation, no additional holding at a typical temperature is required for the crystallization process. As a result, the ceramization process can be made more economical.

It is an essential feature of the invention that is stabilized by reducing the content of minor constituents, the resulting residual glass phase. The resulting disadvantages of a lower tendency to glass formation could be compensated by Al ₂ O 3 or ZrO ₂ additions. It has been surprisingly found that when a certain content of Al2O3 and _ZrO2 (the sum between 1 and 8 mA .-%) is maintained it for forming a stabilized Ca / P-rich reaction corrosion zone at the surface of the bioactive glass-ceramic material comes in the course of lying time in vivo. By in vitro investigations (AES, IRRS measurements) it could be clarified that, in contrast to the known solutions, also other surface structural units than the previously known hydroxylapatite-like ones (OGINO and HENCH, J. Non-Cryst. Solids 38/39 [1980] , 673) can lead to bioactivity, ie direct bone contact. The limitation with respect to the amount content of these two oxide additives results from the fact that at too low levels (less than 1%), the chemical resistance is not significantly increased, ie, no sufficient stabilization is effected. An increase in contents over the range of 8% by mass causes separate, upstream ZrO ₂ or Al ₂ O ₃ layers, which considerably limit the bioactivity of the glass-ceramic material. In this context, it was also found that an addition of Al ₂ O ₃ of greater than or equal to 5.5Ma .-% in addition to low ZrO ₂ additions causes this envelope, ie improving in terms of hydrolytic resistance, but severely limits the bioactivity. The addition of ZrO ₂ with a maximum of 7.5 wt .-% in addition to low Al ₂ O ₃ levels allowed, otherwise there is a formation of a structure that significantly deteriorates the fracture mechanical properties. Furthermore, it has been found that favorable fracture mechanical properties are achieved in the composition range prescribed according to the invention when cristobalite is involved in the structure of the structure as a further crystal phase (up to 15 mass%). The favorable structure of the structure is supported by keeping the Na ₂ O and K ₂ O and MgO contents low and not exceeding the specified upper limit values. The glass-ceramic bioactive material according to the invention can be used as an implant material by itself and can be used as a composite material with bioactive polymers and as a coating material for implant materials made of metal, preferably titanium, tantalum and / or ceramic, preferably of Al ₂ O ₃ ceramic.

embodiments

The invention will be explained in more detail by the following embodiments, but the invention is not limited to these examples.

A mixture is prepared according to a composition It. Table 1, wherein the following components are used:

Tricalcium phosphate, p.a., annealed at 1 300 ° C for 2 h

Calcium carbonate, heavy, p.a., for silicate analysis

Silica (Weferlinger quartz sand, ground, opt. Grade) 'Sodium carbonate, p.a. anhydrous

Potassium carbonate, p.a.

Magnesium oxide, p.a., annealed at 1300 ° C for 2h

Calcium fluoride, p.a.

Zirconia, pure

The quantities required in each case are to be calculated by means of known conversion tables, it being noted that all the P ₂ O ₅ contents indicated in Table 1 are introduced into the mixture in the form of tricalcium phosphate. The remaining remainder of CaO is used as CaCO ₃ .

After suitable homogenization of the mixture, for example with a ball mill, the mixture is melted in platinum crucible, namely 5 h at 1 55O ⁰ C. The melts are then either cast into plates or fritted in water. The casting of the melts takes place in steel molds. The castings are placed in a cooling oven at 700 ° C and cooled to room temperature therein to be sawn or ground thereon to the approximate dimensions of 90 χ 40 χ 5mm. This is followed by ceramization, which is carried out according to the following temperature-time program:

Heating with 1 K · min " ¹ to 92O ⁰ C

Hold at 920 ⁰ C for 24h

Cool in the oven to room temperature.

The measurement of the crack growth curve for the determination of K | _C value takes place on the aforementioned plates. For exact sizing, they are reground on a wet grinding wheel, last with the SiC grain size F28 (20-28μ, ίτι, TGL 29-804). The results obtained on these samples are shown in Table 2. They indicate that

- that biocompatibility is consistently excellent,

- the bioactivity is good to very good,

- the hydrolytic resistance is in classes 2 to 3 and

- the fracture mechanical properties are between 1.6 and 2.59MPa · m ¹ ' ² .

Table 1: Compositions of samples of the embodiments

Execution example

CaO

P ₂ O ₅

SiO ₂

Na ₂ O

K ₂ O MgO

Al ₂ O ₃

CaF ₂

ZrO ₂

31.0

32.5

33.0

31.0

33.55

30.0

31.58

30.98

30.38

10.8

11.4

11.0

11.0

11,45

12.0

11.09

10.87

10.67

43.85

44,95

42.55

45.45

42.4

46.45

44,03

43.78

42,98

3.5 3.5 3.5 1.5 2.5 0.1 4.3 3.5 3.2

0.15

0.15

0.15

0.15

0.1

0.15.

0.15

0.1

0.12

0.1 0.1 2.0 5.0 1.0 0.5 1.0 3.0 5.1

4.9 4.9 1.5 5.1 5.0 2.0 5.0 0.1 3.5 5.0 6.0 1.0 4.95 0.1 4.85 0.2 4.8 0.15

Table 2: Properties of samples of the embodiments

Out Bioeigenschaften Bioakti Hydrolyt. Duration. ¹ ' Vitrokeram Bruchmechan. own managerial biocom- ³¹ WBK (ml0,01nHCI) 3 (0.4) Community mark value example patibil. ²¹ + + Glass 3 (0.5) K, _c MPa -m ^1/2 1 + + + + + 3 (0.85) 3 (0.4) n.d. 2 + + + + + + 3 (0.85) 3 (0.38) n.d. 3 + + + + + 3 (0.33) 2 (0.15) 2.40 4 + + + + + 3 (0.27) 3 (0.22) 2.59 5 + + + + + + , 3 (0.30) 3 (0.51) 1.60 6 + + + + + + 3 (0.28) 3 (0.40) 2.42 7 + + + + + + 3 (0.65) 3 (0.49) 2.55 8th +++ + + 3 (0.60) n.d. 9 + + + 3 (0.52) n.d.

1 according to TGL 14809

2 Cell-toxicological tests and in vitro testing

3> 50 to 70% (+ +) and 70% (+ ++) after 20 weeks of laytime; n.d. - not determined

Claims (6)

Invention claim: 1. Glass-ceramic bioactive material of CaO-P ₂ O ₅ -SiO ₂ -Typ with apatite and wollastonite crystal phase for the alloplastic bone substitute, characterized in that it consists of (calculated on an oxide basis) wherein the sum of CaF ₂ and ZrO _{2 is} 1 to 10% by mass and the sum of Al ₂ O ₃ and ZrO _{2 is} 1 to 8% by mass, having a cristobalite crystal phase as a crystalline minor constituent, and having the following property parameters: Fracture Mechanical Properties: Critical Stress Intensity Factor (K | _C ) between 1.6 and 2.6MPa · m ^1/2 Hydrolytic Resistance (according to standard TGL 14809): 0.15 to 0.85 ml 0.01 η HCl Bioactivity (expressed in terms of the size of the contact area between bone and implant after one year's laytime in%): up to 80% biocompatibility: - no cytotoxic reactions in different cell cultures - Detectable inflammation-free ingrowth in the hard tissue. 2. Glass-ceramic bioactive material according to claim 1, characterized in that it contains 31.58% CaO, 11.09% P ₂ O ₅ , 44.03% SiO ₂ , 4.3% Na ₂ O, 0.15% K ₂ O, 2.8% MgO, 1.0% Al ₂ O ₃ , 4.95% CaF ₂ and 0.1% ZrO ₂ (data in% by mass). 3. A process for the preparation of a glass-ceramic bioactive material of CaO-P ₂ O ₅ -SiO ₂ -TyP with apatite and wollastonite crystal phase for the alloplastic bone substitute, characterized in that a mixture according to the composition (on oxide basis and in Ma. % calculated) according to claim 1 into a glass, - the molten glass deforms or frit and the molded or fritted glass - a temperature-time program Heating with a lying between 0.1 and 1OK · min "" ¹ speed to between 85O ⁰ C and 1 050 ⁰ C lying temperature and maintaining this temperature between 10 minutes and 48 hours and Cool down to room temperature with a rate of between 1 and 2OK · min ^-1 . 4. Use of the glass-ceramic bioactive material according to claim 1, characterized in that it is used for alloplastic bone replacement. 5. Use according to claim 4, characterized in that the glass-ceramic bioactive material as a coating material for implant materials made of metal, preferably titanium, tantalum and / or ceramic, preferably as Al ₂ O ₃ ceramic, is used. 6. Use according to claim 4, characterized in that the glass-ceramic bioactive material is used as a composite material with bioactive polymer.