DE4113021C2 - Resorbable phosphate glasses and resorbable phosphate glass ceramics, process for their preparation and use - Google Patents

Description

The resorbable phosphate glasses according to the invention and resor Bable phosphate glass ceramics can be used in particular as biomas terials used in medicine and biology, wherein the application as Hartgewebs- or bone replacement that before termed application.

It is known that various glasses, glass ceramics and Sintered ceramics as bone replacement materials in medicine be used (DE 28 18 630, US 41 03 002, DE 23 26 100, DE 33 06 648, DE 35 00 287, US 46 98 318). These materials are considered bioactive, d. H. they grow together with the living Bone under formation of a chemical-physical Ver nationwide. Because these bone replacement materials in the long run their radio show that they can fulfill their role as an implant in the organism in addition to good compatibility usually a good long time stability against the attacks of the body fluid. Although some of these materials are for certain use areas in medicine has proven to be very good limited and possible for these materials a number of indications are such implants only conditionally or not applicable.

Since the use of resorbable bone chenersatzwerkstoffe is promising for many such cases, a number of dense or porous resorbable implant materials have already been developed, which are absorbed after a certain period of time in the bone and replaced by newly formed bone. However, the use of resorbable implants requires that the ions released in the living organism upon dissolution of the implant have no toxic or carcinogenic effect. Since the mineral content of human bone consists essentially of calcium phosphates, it is understandable that previously sintered calcium phosphates, mostly β-tricalcium phosphate, β-Ca ₃ (PO ₄ ) ₂ , individually or in admixture with hydroxyapatite, Ca ₅ (PO ₄ ) ₃ OH, were in the foreground (eg, US 41 95 366, Z. Orthop. 115 (1977) 604, J. Mat. Sci 17 (1982) 343, DE 38 31 260, DE 36 13 213, etc.). The sintered ceramics based thereon are more or less absorbable and are currently being clinically used with some success. All recently, the lack or lack of controllability of the absorption rate and thus the lack of Anpas solution to new bone formation and the Knochenwachstumsge speed and the risk of detachment of individual ceramic grains that can challenge the organism to foreign body reactions, as serious disadvantages.

Resorption phenomena on phosphate glass ceramics after implantation in experimental animals are reported by Pernot et al. (Cereals International, 9 (1983) 4, 127-131). They developed porous metaphosphate-based glass ceramics in the system CaO-Al ₂ O ₃ - P ₂ O ₅ , which contain calcium metaphosphate, Ca (PO ₃ ) ₂ as the crystal phase. The pores of the material are completely penetrated by newly formed bone and resorption is observed on the surface. There is no information available on complete dissolution of the material in the living organism. Due to the relatively high Al ₂ O ₃ content of the glass-ceramics, this is not to be expected either.

Courpied et al. (Internat. Orthopedics, 6 (1982) 1-7) investigated metaphosphate glasses in the system CaO-P ₂ O ₅ -Na ₂ O-BaO-MgO-B ₂ O ₃ and were able to detect resorption phenomena in animal experiments. However, the material contains considerable amounts of foreign body ions, which would make the use of these materials as resor bierbares implant at least as a concern (Ba ²⁺ , B ₂ O ₃ ).

Berger and co-workers (Silikattechnik 41 (1990) 6, 194-198) report on absorbable phosphate glass ceramics in the system CaO-Na ₂ OK ₂ O-MgO-SiO ₂ -P ₂ O ₅ with high solubility. The low P ₂ O ₅ content of 30-50% by mass, however, leads to the fact that no glasses are obtained and the crystallization of the described materials takes place spontaneously from the liquid melt. Thus, a precise control of the crystal phase content and thus the solubility behavior is not possible.

Hosono et al. developed porous glass ceramics for technical applications by the selective leaching of individual crystal phases of glass ceramics of the systems Na ₂ O-CaO-TiO ₂ -P ₂ O ₅ or Na ₂ O-CaO-TiO ₂ -P ₂ O ₅ -SiO ₂ (J. Electrochem, Soc., 137 (1990) 10, 3149-3151 and J. Am. Ceram Soc 73 (1990) 8, 2536-2538). While in the first case by aqueous HCl solution present in the glass ceramic crystal phase β-Ca ₃ (PO ₄ ) ₂ leached and the stable NaTi ₂ (PO ₄ ) _{3 forms} the framework of the porous ceramic, in the second case to the same The CaNaPO ₄ phase is dissolved out, and the porous ceramic consists of rutile and anatase. However, these porous glass ceramics are not re sorbable and the achieved pore diameter (up to about 2 microns) is too small for the ingrowth of bone.

Most other studies have become known Set of phosphate glasses and phosphate glass ceramics in the Medicine is aimed primarily at long-term stable mate sometimes high-strength materials (JP 55-11 625, DE 31 42 813, JP 60-28 911 a. a.).

To produce open-pored glass or glass ceramic body various methods are known, many focusing on sintering of mixtures of glass or glass ceramic powders with organic Refer to substances or soluble inorganic salts (DE 31 03 751, DE 33 05 854, EP 01 17 484, DE 37 31 649). In the first case, the porosity by burning out of the organic Shares reached. This affects the relatively large Temperature differences between the decomposition temperature of organic component and the necessary sintering temperature of the glass is usually negative. In the second case will be the respective salts after the sintering process as far as possible washed out. This procedure offers several possibilities the influence on the sintering process and the achieved Porosities are controllable within limits. Through the use of Glass ceramics or the crystallization of the sintered body can increases the strength of the porous materials in some cases become.

The aim of the invention is to avoid the after Parts of the prior art, the bone largely adapted resorbable implant material based on Phosphate glasses and phosphate glass ceramics with adjustable To provide solubility and absorption time.

This object is achieved according to the invention as in claim 1 sets, solved by the resorbable phosphate glasses and the resorbable phosphate glass ceramics the composition

P₂O₅ 27.1-39.9 mol% CaO 22.5-36.0 mol% R₂O 14.5-30.0 mole% MgO 5.0-25.0 mole%

in which R ₂ O contains 11.4-30.0 mol%, Na ₂ O and 0-12.0 mol% K ₂ O and the phosphate glass ceramic contains calcium orthophosphate and / or calcium diphosphate and / or sodium diphosphate as main crystal phases. The resorbable phosphate glasses and phosphate glass ceramics may have a dense or porous structure. While the solubility of the resorbable phosphate glasses is determined by the chemical composition and the targeted influencing of the structure of the glasses, the targeted and controlled crystallization of calcium orthophosphates and / or calcium diphosphates and / or sodium diphosphates or other secondary crystal phases to control the solubility of the resorbable phosphate glass ceramics on. This also applies if the glasses and glass ceramics according to the invention TiO ₂ , SiO ₂ , Al ₂ O ₃ , F ^- , Cl ^- individually or together within the limits

TiO₂ 0-6.5 mol% SiO₂ 0-4.0 mol% Al₂O₃ 0-2.5 mol% F ^- 0-6.0 mol% Cl ^- 0-3.0 mol%

contain.

The glass and glass ceramic material according to the invention is made a starting glass melted between 1150 ° C-1550 ° C produced, which is below the transformation temperature controlled cooled, by casting on a cold object quenched or fritted by pouring into cold water. The production of the resorbable phosphate glass ceramic takes place by a subsequent thermal treatment of the output glass in the temperature range between 450 ° C-800 ° C in one or more intervals.

Porous resorbable phosphate glasses and phosphate glass ceramics be through a special post-treatment and Weiterverarbei received. For this purpose, the starting glass to a grain size crushed between 20 microns and 550 microns and with a light soluble, relatively high melting salt, z. B. NaCl, one  Grain size between 20 microns and 550 microns intimately mixed. That so obtained phosphate glass salt mixture is then in a Shape between the transformation point (Tg value) of the glass and 800 ° C sintered with or without pressure for 5 minutes to 24 hours. The resulting sintered body is cooled to room temperature and the salt component in water or another suitable one Solvent at temperatures between room temperature and Leached 100 ° C. The remaining sintered body shows in dependence from the chosen glass-salt ratio a porous one Structure. The pore diameter is determined by the grain fraction used of the salt. Possible isolated salt grains, which are thus not detected in the leaching process are meaningless, especially when using NaCl for later use. They are from the at Resorption of the material penetrating into the interior of the implant Body fluid dissolved.

Another possibility for creating porous structures of the glasses and glass ceramics according to the invention consists z. Example is that the molten and crushed starting glass with CaCO ₃ or other suitable inorganic or organic foaming agent in place of the salt is added and mixed. The gases released by the decomposition of the foaming agent during subsequent sintering foam the material and result in a porous structure. A subsequent leaching process is not necessary here. The production of porous resorbable phosphate glass ceramics is carried out by the subsequent thermal treatment of the described glassy sintered bodies in the temperature range between 450 ° C-800 ° C or by a targeted control of the crystallization during the sintering process. In general, the ceramization can be done in one or more steps.

Other methods of producing porous glasses of the invention ser and glass ceramics, such. B. the storage and the off burning organic fibers are possible.

Regardless of the way of making the porous absorbable Phosphate glasses and phosphate glass ceramics are based on these their porosity can be worked with simple tools.

The glasses and glass ceramics according to the invention are highly P ₂ O ₅ and CaO-containing materials which, in their chemical composition and in their phosphate structure elements, are generally adapted to the bone in general, in particular in their porous form to the spongy bone. Quantitative ³¹ P nuclear magnetic resonance studies have shown that the structure of glasses and glass-ceramics is determined by small phosphate moieties, mainly ortho and diphosphate moieties. A part of the glasses shows a pure inverted glass structure. The subsequent tempering of the glasses for the production of glass-ceramics additionally leads to the cleavage of POP bonds and increases the proportion of small phosphate structural elements in the resulting glass-ceramics compared to the starting glasses.

This phosphate structure causes the inventive Phosphate glasses and phosphate glass ceramics on changes in the Synthesis or react to additives very sensitive and thus one over conventional phosphate glasses based on metaphosphate with a more or less entangled phosphate chain structure enable better control of the solubility behavior. lös in vitro using simulated Body fluids confirm the over large areas freely adjustable solubility and leaching rates.

The subsequent thermal treatment of the glasses described leads, without phase separation phenomena could be detected in the glasses, for the crystallization of calcium orthophosphates, mainly Whitlockit, and / or Kalzi umdiphosphaten and / or Natriumdiphosphaten. The precipitation of whitlockite, (Ca, Mg) ₃ (PO ₄ ) ₂ or derived kri stalliner calcium orthophosphate phases is possible by the crystal phase stabilizing effect of the MgO content of the glasses and can be controlled by the addition of small amounts of Al ₂ O ₃ , This also applies to the addition of TiO ₂ . In contrast to the usually nucleating effect of TiO ₂ in glasses, however, the TiO ₂ in the glasses according to the invention acts to strengthen the glass structure. X-ray diffraction studies revealed calcium orthophosphates with different Mg contents depending on the composition of the glasses and the type of thermal treatment. You can also contain sodium and potassium ions individually or together.

The precipitated calcium diphosphates can occur both as pure calcium diphosphate in α- and / or β- and / or γ-form, as well as in the form of mixed calcium-sodium (Magne sium) diphosphates, which additionally contain potassium ions. The sodium diphosphate, which has also been detected by X-ray diffraction studies and ³¹ P nuclear magnetic resonance studies, preferably crystallizes in addition to whitlockite from glasses with increased Na ₂ O content and may likewise contain magnesium and / or potassium and / or calcium ions.

Besides these, the main properties of the absorbable phos phatglas ceramics essentially determining crystal phases Kings NEN glass ceramics according to the invention also other side contain crystal phases whose investigation z. T. not on indicates stoichiometric, complex structures.

With the development of the absorbable Phos phat glasses and phosphate glass ceramics have succeeded, Materia lien, as a bone substitute material, in their porous form primarily to replace spongious bone, suitable are net. The materials are relative to their absorption Duration and solubility adjustable so that they (in the Sprouting pores) Bones as a guide rail for the bones can provide new education and give him enough time (about 1.5 years) to mineralization and maturation, but on the other hand be completely absorbed without the dissolution of the materials liberated ions lead to toxic side effects. Due to their chemical composition, the inventive resorbable phosphate glasses and phosphate glass ceramics an ion depot represented by the continuous Delivery of physiological ions during the absorption process promote the growth and mineralization of the bone can. The resolution into granular single particles becomes special avoided in the absorbable phosphate glasses.

The embodiments in Table 1 give an overview on possible selected compositions of the invention resorbable phosphate glasses and absorbable phos phatglaskeramiken.

The crystalline phase of the phosphate glass according to the invention ceramics is shown in Table 2 on selected examples of Table 1 depending on the thermal treatment.

An exemplary embodiment for producing porous resorbable phosphate glass ceramic is described below:
According to the composition 18 of Table 1, a Glasroh material mixture of calcium metaphosphate, magnesium metaphosphate, magnesium carbonate, alumina hydrate and soda is melted in platinum crucible at 1300 ° C in an electrically heated oven and refined at 1300 ° C for 1 hour. The liquid glass is fritted in cold water, then dried and comminuted to a particle size between 40 .mu.m-70 .mu.m. The glass powder thus obtained is added in a volume ratio of glass: sodium chloride of 1.5: 1 sodium chloride of the grain fraction 250 .mu.m-315 .mu.m and both intimately mixed. The glass powder-salt mixture is heated in a mold in a special oven to 750 ° C and sintered under a pressure of 3 bar for five hours. From the abge cooled sintered body is obtained by leaching of the salt in What ser at room temperature a pervasive pervasive phosphated glass ceramic in addition to the residual glass phase Whitlockit, (Ca, Mg) ₃ (PO ₄ ) ₂ , a mixed calcium sodium diphosphate phase and a containing aluminum-containing complex phosphate phase.

Table 1

(in mol%)

Table 2

Claims (9)

1. Resorbable phosphate glasses and absorbable phosphate glass-ceramics, characterized in that they the composition P₂O₅ 27.1-39.9 mol% CaO 22.5-36.0 mol% R₂O 14.5-30.0 mole% MgO 5.0-25.0 mole% wherein R ₂ O contains 11.4-30.0 mol% Na ₂ O and 0-12.0 mol% K ₂ O, the resorbable phosphate glass ceramics in addition to the glass phase, the main crystal phases calcium orthophosphate and / or calcium diphosphate and / or sodium diphosphate contain th and the resorbable phosphate glasses and resorbable ble phosphate glass ceramics have a dense or porous structure. 2. Resorbable phosphate glasses and resorbable phosphate glass-ceramics according to claim 1, characterized in that they are the additional components TiO ₂ , SiO ₂ , Al ₂ O ₃ , F ^- , Cl ^- , individually or together within the limits TiO₂ 0-6.5 mol% SiO₂ 0-4.0 mol% Al₂O₃ 0-2.5 mol% F ^- 0-6.0 mol% Cl ^- 0-3.0 mol% contain. 3. resorbable phosphate glasses and resorbable phosphate glass-ceramics according to claims 1 and 2, characterized in that in the latter, the calcium orthophosphate magnesium ions and / or
Sodium ions and / or
Contains potassium ions. 4. Absorbable phosphate glasses and absorbable phosphate Glass ceramics according to claims 1-3, characterized in that in the latter, the calcium diphosphate phase in the α- and / or β- and / or γ-form. 5. resorbable phosphate glasses and resorbable phosphate glass-ceramics according to claims 1-4, characterized in that in the latter the calcium diphosphate sodium ions and / or
Magnesium ions and / or
Contains potassium ions. 6. resorbable phosphate glasses and resorbable phosphate glass-ceramics according to claims 1-5, characterized in that in the latter the sodium diphosphate magnesium ions and / or
Potassium ions and / or
Contains calcium ions. 7. Use of the resorbable material according to the claims 1-6 as a compact body, as a porous body or as a compact one or porous granules in medicine and biology. 8. Process for the preparation of resorbable Phosphatglä and absorbable phosphate glass ceramics according to claims 1-7, characterized in that the absorbable phosphate glasses in the temperature range between 1150 ° C-1550 ° C he become molten and the resorbable phosphate glass ceramics through a one- or multi-stage annealing process of the resorbier phosphate glasses in the temperature range between 450 ° C and 800 ° C, preferably in the temperature range between 550 ° C-750 ° C, be prepared and a porous structure by it can be generated that the molten glass a nachträg subjected to sintering process. 9. Process for the preparation of resorbable Phosphatglä and absorbable phosphate glass ceramics according to claims 1-8, characterized in that a porous structure characterized is generated that a resorbable starting glass on a Grit size between 20 microns-550 microns comminuted and with a easily soluble salt, preferably NaCl, of a grain size between 20 μm-550 μm and then mixed with a or multi-stage sintering process with or without pressure at temperatures between 450 ° C-800 ° C is subjected and a subsequent Leaching of the salt component by a solvent, preferably water, at temperatures between 15 ° C-100 ° C. takes place, wherein the preparation of absorbable phosphate glass ceramics with porous structure by a subsequent Annealing the glassy sintered body before or after leaching the salt component in the temperature range between  450 ° C-800 ° C or by crystallization of the starting glass component during sintering.