MXPA97003291A - Process for the production of spongeous bone ceramics that has low oxid content of cal - Google Patents

Abstract

The present invention relates to a process for the production of spongy osseous ceramics with a low calcium oxide content. Between the mineralization of the matrix and the sintering to a ceramic, an extractive washing operation is carried out using demineralized water, by means of which the calcium oxide components are removed from the matrix mineralized

Description

PROCESS FOR THE PRODUCTION OF SPONGEOUS OSTE CERAMIC THAT HAS LOW CALCIUM OXIDE CONTENT DESCRIPTION OF THE INVENTION The invention relates to a process for the production of spongy bone ceramics with a low content of calcium oxide. It has been known for a relatively long time that the mineralized bone that has been sintered to form a ceramic is ideally suited as a bone replacement material. With bone ceramics there is naturally a very high degree of correspondence in chemical composition, structural composition and mechanical strength with natural bone. In addition, spongy bone ceramics have been found to be particularly osteoconductive. The open, interconnected and trabecular structure of the spongy bone ceramic promotes the growth of the new bone matrix on and within the ceramic, so that during the incorporation there is an intense colonization and therefore integration of the ceramic implant. Bone ceramics produced from bones of animal origin are therefore increasingly used as replacement materials REF: 24483 bone in osteosynthesis and in the reconstruction of bone defects caused by disease or accident. The production of bone ceramics from the bone of an animal is generally carried out by first releasing the bones or selected bone parts, mechanically, from all the soft adhered parts, then cutting these bones or bone pieces roughly to size by sawing, to Give pieces of appropriate shape and size, which are then mineralized by removing all other organic components. The process of mineralization begins first of all with the bones that are boiled several times in water. Subsequent treatment can be carried out, for example, with solvents that dissolve fats or solvents that dissolve proteins, and / or with the help of hydrogen peroxide, as described for example in European Patent EP 0,141,004. The methods that have proved particularly simple and effective are those of pyrolytic mineralization, in which the action of heat decomposes the organic component of the bone and the resulting carbon is subsequently burned to completion, in excess of oxygen. For bone pyrolysis, temperatures between 500 and 1000 ° C are common. After the mineralization of the bone, it is sintered to give the ceramic, with temperatures between 800 and 1400 ° C, which are common. It is only through sintering that the material acquires the desired final strength. In the course of the mentioned procedures, particular care must be taken to ensure that the porous structure of the original bone is preserved, as much as possible. For the conversion of spongy bone material to spongy bone ceramic, a preferred option is to proceed according to the process described in German Patent DE 37,27,606, in which a specific temperature regime and the reducing or oxidizing character of the atmosphere makes possible the particularly smooth pyrolysis. It has been found that bone ceramics have a tendency to uncontrolled instability if the main phase, hydroxyapatite, exists along with remarkable amounts of calcium oxide, which can be detected, for example, by X-ray analysis. This is the case when the calcium oxide content is greater than 5%. The inflow of water, for example in the form of atmospheric moisture in the course of unprotected storage or in the organism after the implant procedure, is accompanied by the successive transformation of calcium oxide to calcium hydroxide, which involves an increase considerable in volume. Depending on the proportional content, this process can be extended until the ceramic breaks completely. The proportion of calcium oxide in bone ceramics is a natural parameter, and can vary with the individual nature and bleeding of the animal. Calcium oxide is formed by calcium carbonate, which is naturally present in the bone undergoing conversion, in the course of pyrolysis and sintering, to calcium oxide. German Patent DE 40,28,683 proposed the treatment of the mineralized bone material, before sintering, with an aqueous solution of an organic acid, especially citric acid. This step leaches the calcium oxide components out of the material, so that the bone ceramics obtained after the sintering has, according to the X-ray analysis, a hydroxyapatite content of more than 99%. Although this method is highly effective and leads to a stable, useful bone ceramic, this is not without disadvantages. These disadvantages lie mainly in the area of operation of the process regime. Thus, in the case of pyrolytic mineralization in particular, the material must first be cooled to room temperature again in order to make it possible for the acid treatment and the necessary rinsing operations to be carried out. After this, the material must be heated again from the starting line for sintering. These operations consume time and are of intense energy. In addition, the preparation and consumption of the acid solution and the consumption of water for rinsing, for washing the material until neutrality, increase production costs. In addition, the control and periodic verification of the acid treatment step is not simple. On the other hand, it must be ensured here that virtually all calcium oxide is leached, while on the other side little or none of the hydroxyapatite matrix material must be attacked by the acid. The fine spongy structure at this point in the process, has not yet undergone sufficient solidification, and is therefore highly sensitive. The object of the present invention was therefore to reduce the aforementioned disadvantages of the previous method.

Surprisingly, it has now been found that the calcium oxide components, present in the mineralized bone matrix, can be easily removed if the bone matrix is subjected to a washing operation with demineralized water at a temperature of from 10 to 80 [deg.] C., a period of 4 hours to 7 days. The leaching of calcium oxide using acid, especially aqueous solution of citric acid, has therefore been found to be unnecessary. The invention thus provides a process for the production of spongy bone ceramics with a low content of calcium oxide, in which process the spongy bones cut into pieces, are mineralized by removing all the organic constituents, and then the bone matrix mineral is sintered to the ceramic, whose process is characterized because, in order to eliminate the calcium oxide components of the mineralized bone matrix, the latter is subjected to extractive washing with demineralized water at a temperature of 10 to 80 ° C, in a period of 4 hours to 7 days. The process according to the invention is carried out in practice, in complete analogy to that known from German Patent DE 40,28,683. The only difference here is that the treatment step with "acid provided between the mineralization of the bone material and the sintering for a ceramic, is replaced by a treatment with demineralized water.Demineralized water is known per se and is readily available. It can be prepared in any desired quantity by means of generally known methods, from natural water, for example by simple or multiple distillation and / or removal of the dissolved mineral salts, using ion exchanges. Slightly acidic pH of approximately 6.0 It is assumed that this slightly acid character of the demineralized water favors the extractive washing of calcium oxide from the mineralized bone matrix For the extractive washing operation it is sufficient to transport the mineralized bone material, cut into pieces , towards a bath of appropriate dimensions of desmin water eralized, and leave it there for a time that seems to be sufficient and expedient at an appropriate temperature. The circulation or agitation of the water bath can contribute to the leaching of the soluble constituents. It has been found appropriate and necessary to use a ratio of 10 liters of water per kg of bone material, and a treatment duration of 4 hours 7 days, at a bath temperature of between 10 and 80 ° C. The change of water for washing one or more times, or continuous jet washing with fresh demineralised water, has a beneficial effect on the result, and may shorten the treatment time. The procedure indicated makes it possible that virtually all the calcium oxide content present, or that is expected to be in the bone matrix, is eliminated, essentially without residue. In general, the natural amount of calcium oxide in the bone varies between 5 and 10%. Through the analysis with X-rays on the ceramics obtained at the end, it is found that the material has a hydroxyapatite content of more than 95%, and in general from 97 to 99%. Calcium oxide can only be detected in traces if it is possible. The process according to the invention makes it possible to save considerable amounts of the acid, which has been required to date to achieve a comparable result. In addition, subsequent rinsing operations are omitted to wash the material to neutrality, thereby providing additional savings in cost and time.

In addition, the process according to the invention is substantially milder, since the hydroxyapatite matrix is not attacked by treatment with demineralized water. After the completion of the extractive washing operation, the pieces are dried and then sintered to ceramic, in a conventional manner.

Example The raw heads of bone, freed from the soft parts, from freshly slaughtered cattle are cut with saw in rectangular pieces, with dimensions of approximately 30 x 30 x 100 mm, which are boiled with water three times for approximately 1 hour. The bone pieces are then dried at 110 ° C for 6 hours. These are then heated under a nitrogen atmosphere at 450 ° C in the course of 9 hours. During a subsequent heating period of 20 hours from 450 ° C to 600 ° C, the atmosphere is changed in a linear progression to atmospheric oxygen, and heating is continued at 900 ° C in the course of 5 hours. After cooling, the pieces are placed in a bath of demineralized water (10 liters per kg of bone material) and treated in the stirred bath at a temperature of 20 ° C for a period of 48 hours. After this treatment, the pieces are rinsed three times with demineralized water. For the final sintering, the pieces are heated to 1250 ° C in the course of 21 hours, kept at this temperature for 3 hours, and then left to cool. The resulting bone ceramic pieces show the porous structure without change of the original cancellous bone. According to X-ray analysis, the ceramic has a hydroxyapatite content of approximately 99%.

It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Having described the invention as above, property is claimed as contained in the following:

Claims (1)

1. A process for the production of spongy bone ceramics with a low content of calcium oxide, in which process the spongy bones cut into pieces are mineralized by eliminating all the otganic components, and then the mineralized bone matrix is sintered to a ceramic, characterized in that, in order to remove the calcium oxide components from the mineralized bone matrix, it is ultimately subjected to extractive washing with demineralised water at temperatures from 10 to £ ° in a period of 4 hours to 7 days.