CH664280A5 - INORGANIC IMPLANT MATERIAL AND METHOD FOR THE PRODUCTION THEREOF. - Google Patents

Description

DESCRIPTION

The invention relates to an inorganic implant material which is intended for implantation in the living body, which shows excellent compatibility with the living body, does not cause a noticeable foreign body reaction and has improved ability to promote the formation of new bone.

In surgical and orthopedic treatments, it is often necessary to fill defects or cavities in bones in prosthetic operations caused by complicated bone fractures or by surgical removal of bone tumors. To solve this problem, it is common practice to remove bone tissue, such as ilium and the like, from the patient to fill the defect or cavity of the bone and thereby promote early healing of the bone tissue. In such an operation, however, normal bone tissue must be removed from an intact area, which causes additional pain to the patient in addition to the great difficulties caused by the operation. In addition, if the volume of the defect or cavity in the patient's bone is large, the amount of bone that can be extracted from his own body is not always sufficient to completely fill the defect or cavity. In such a case, it is essential to use a replacement material for the patient's own bone tissue, this replacement material being chosen from the same bone tissue or a different type of bone tissue. With regard to the implantation of the same type of bone, studies have been made on the use of bone stored in the frozen state and the use of decalcified bone. So far, however, these types of bones have not been considered practical implant materials. On the other hand, so-called keel bone, i.e. a material made by removing proteins from bovine bones is sometimes used as a different type of implant bone. However, both of the aforementioned types, i.e. the same or a different type of bone tissue, a foreign body rejection reaction or other difficulties cause and show only slight bone formation ability. For these reasons, postoperative healing of the

Defect is not always satisfactory. Another measure that is usually used to shorten the time required to heal the bone defect is the internal fixation method, in which the broken area is fixed directly with the help of a metal plate, a nail or a screw. In many cases, however, a long time from six months to a year or even longer is required for complete healing, even if such an internal fixation method is used. In addition, the material used for the internal fixation must be removed from the patient's body after the fracture has healed completely, as a result of which the patient suffers from extraordinary physical pain, mental strain and economic disadvantages.

i5 Numerous metallic and plastic materials have already been used as a substitute for the hard tissues in the living body. However, it has been recognized that these materials have a tendency to dissolve or otherwise degrade in the vicinity of living tissue or that they are toxic to the living body and cause so-called foreign body reactions. Ceramic materials have attracted general attention because of their excellent compatibility with living tissues. More recently, artificial bones, joints or roots made of single-crystal or polycrystalline aluminum oxide (AI2O3) have been proposed, as well as an artificial root made of a sintered product of tricalcium phosphate Ca3 (PO, 02 or hydroxyapatite 30 (Ca5 (P04) 30H) it has been reported that these materials have excellent compatibility with the living body and that, for example, a sintered product made of hydroxyapatite which is implanted in living bone tissue does not lead to the formation of a foreign material membrane, which shows that the implanted sintered product combines directly with the bone tissue However, it has not yet been clarified what types of ceramic implant materials must be used to enable no or minimal foreign body response, excellent living body compatibility, and early new bone formation to be achieved .

The invention is therefore based on the primary object of providing an inorganic implant material 45 which is improved, in particular with regard to compatibility with the living body, causes little or no foreign body reaction and which forms the formation again within a very short period Stimulates bone tissue.

It is also an object of the invention to provide an inorganic implant material which promotes the formation of bone tissue in the implanted part, so that the structure and function at and near the defects in the bone tissue or at the point where, more likely the bone tissue is fixed, recovered and healed.

Another object of the invention is to provide an inorganic implant material with the help of which the formation of new bone takes place very early. 60 The foregoing and other objects and objects of the invention will be fully apparent from the following description.

The invention relates to an inorganic implant material which comprises an inorganic material with a negative zeta potential.

The invention is described in detail below. The "zeta potential" used for definition in the claims and the description is determined with the aid of the

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Method for determining the flow potential measured. For this purpose, the sample to be subjected to the determination is finely pulverized and poured into a test cell in the form of a diaphragm. A liquid is forcibly passed through this diaphragm with the aid of an inert gas, such as nitrogen gas, as the pressure source, the potential difference between the end faces of the diaphragm-shaped sample being measured. The zeta potential is calculated using the following equation (Helmholtz-Smoluchowski equation), using the pressure applied for P and the measured potential difference for E:

Zeta potential = ilHAE—;

eP '

Therein t) means the viscosity coefficient (10-1 Pa • s) of the liquid, X the specific conductivity (fi-1 cm-1) of the liquid, e the dielectric constant (-) of the liquid in air, E the measured potential difference limit (mV) and P the applied gas pressure (cm H2O).

In view of the compatibility with the living body, it is preferred to use a glass containing calcium phosphate or a calcium phosphate compound as a main component as the inorganic material, although the present invention is not limited to the use of such a glass or a calcium phosphate compound, provided that that the inorganic material used has a negative zeta potential if this is measured using the determination method for the flow potential, and provided that the material is not toxic to the living body.

Examples of suitable calcium phosphate compounds include tricalcium phosphate, tetracalcium phosphate, hydroxylapatite, fluoroapatite, animal bones and mixtures of such materials. These materials are preferred because they have the same or similar composition as the inorganic composition of the hard tissue in the living body and therefore show excellent compatibility with the living body. Among these materials, hydroxylapatite is the most preferred material because its composition is the same as that of the hard tissue of the living body.

Other preferred materials include glasses containing calcium phosphate as a main component and having a Ca2 + / P043 ~ atomic ratio in the range of 0.2 to 3.0 and a CaO plus P2O5 content of not less than 15% by weight.

For the purposes of the invention, any inorganic materials, each having a negative zeta potential, can be used, regardless of whether they have been synthesized using the known methods or occur in the form of natural sources, such as animal bones, phosphorus minerals or fulorapatite .

In order to obtain an inorganic material which has a negative zeta potential according to the invention, if the inorganic material is a calcium phosphate compound, the calcium phosphate compound used as the starting material should be calcined at 500 ° C. or above and the total proportion of inorganic metal ions, such as Mg2 +, Al3 + or Si4 +, in the inorganic material should be 10% by weight or less, preferably 5% by weight or less, calculated as MgO. If a glass predominantly composed of calcium phosphate is used, the melting temperature during the production of this glass should be set to a temperature value of 800 to 1700 ° C. and the total content of inorganic oxides,

except for CaO and P2O5 such as Na20, MgO, AI1O3, SÌO2, Fe203 and TiOo, should be set to less than 85% by weight.

Among the above-mentioned inorganic materials are those with a zeta potential in the range of - (minus) 0.05 to - (minus) 20.0 mV, in particular - (minus) 0.2 to - (minus) 10.0 mV preferred because they show superior compatibility with the living body and lead to an earlier formation of new bone, the zeta potential being determined with the aid of the method for determining the flow potential, according to which distilled water is used as the liquid which is produced by the in the inorganic cell filled with the test cell and subjected to the test flows.

The shape of the inorganic implant material according to the invention is not limited, provided that it shows a negative zeta potential when it is pulverized into a powder and subjected to the determination method explained above. For example, it can be used in the form of powder, granules, porous bodies, plates, cylindrical or rectangular columns, in truncated form (including truncated cone shape, truncated triangular and truncated polyhedral shape) or in fiber form.

If the inorganic implant material according to the invention is used in the form of powder, an inorganic starting material produced by means of a known method can be pulverized and used directly as filler material or can be filled in in the form of a slurry with the addition of an isotonic sodium chloride solution or blood. It can also be used in the form of grains. An inorganic material that has already been pulverized thoroughly to form a fine powder can be shaped into grains using the shell granulation method and these grains are suitable for direct filling in the form of the granulate, in the same way as in the case of the powder, or the Grains can be wetted by adding an isotonic sodium chloride solution or blood before filling.

When the material according to the invention is used in the form of a porous body, it can be produced by calcining a spongy bone taken from a living body or by means of a method according to which a slurry of powdery inorganic material is adhered to a porous organic Body is brought and then the organic material is removed by burning. The porous body produced with the aid of the last-described method is advantageously used as a filler for filling in defects or cavities in bones, since new bone tissue grows in the lower part in the porous body implanted in this way, as a result of which the implant material is connected to the growing living tissue earlier is promoted than when using a dense implant material produced by sintering.

For use in the form of a flat plate, a powdery inorganic material is deformed and then sintered, forming a plate which is suitable for applications in which particularly high strength is required, such as in the case of a plate for fixing bone.

Cylindrical, rectangular columnar and circular or square frustoconical implant materials can be made using a method similar to that used to make a plate. Products of such a configuration can, for example

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can be used as nails or screws to fix bone.

The inorganic implant material according to the invention can be used not only in the field of orthopedics, but also in the field of dental treatment. For example, it can be used in the form of powder, granules or porous bodies to cure the pyorrhea alveolaris of periostitis alveolaris and can be in the form of a cylindrical, square or rectangular columnar body with a truncated shape (including a truncated body with a circular, triangular shape). square or polyhedral base) can be used as a dental pen for filling into a tooth root canal.

The invention is described below using examples.

example 1

Using distilled water as the liquid which is passed through the samples filled into a test cell, the zeta potential of various samples was measured using a device for determining the flow potential (model ZP-10B from Shimazu Seisakusho Ltd.). The zeta potential of each of the following samples was determined: calcined powder from a bovine bone that consisted only of inorganic components (organic components had been removed by calcining at 900 ° C.); calcined powder of tricalcium phosphate (calcined at 1000 ° C., content of inorganic metal ions: 0.2% by weight, calculated as MgO); calcined powder of hydroxyapatite (calcined at 900 ° C, content of inorganic metal ions: 0.3% by weight, calculated as MgO); Tetracalcium phosphate (calcined at 1350 ° C, content of inorganic metal ions: 0.4% by weight, calculated as MgO); calcined powder of titanium oxide (content of inorganic metal ions other than titanium: 0.1% by weight, calculated as MgO).

The results are shown in Table 1.

Table 1

Material zeta potential

5 calcined beef bones -0.6

Tricalcium phosphate -0.4

Hydroxyapatite -0.6

Tetracalcium phosphate -0.3

Titanium oxide -0.3

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Each of the above powdery materials was filled in a defect which had been artificially formed in the femur of a rabbit and whose dimensions corresponded to a diameter of 3 mm and a length of 4 mm. New bone formation was observed in the filled area one month after the implantation in the cases where the implantation was performed with the above-mentioned materials. In each of the cases in which the samples formed by calcining bovine bone and hydroxyapatite were used, the defect was completely healed, with a large volume of newly grown bone tissue being formed. When using tricalcium phosphate or tetracalcium phosphate er-25, the volume of newly grown bones in the defects reached a value that was closest to the cases of bovine bone and hydroxyapatite. The degree of healing that can be achieved with the use of titanium oxide is quite low compared to the other cases, although 30 newly grown bones have also been observed.

Example 2

Hydroxyapatite samples were synthesized by the wet method under the conditions shown in Table 2 below, and the zeta potentials of the obtained samples were measured in the same manner as in Example 1, using distilled water as the passed liquid. The information identified with MgO in Table 2 means the content of inorganic metal ions, calculated as MgO.

Table 2

sample

Name of the sample

Calcination

Zeta

No.

teraperature (C)

Potential (mV)

1

Hydroxyapatite (MgO, 0.3% by weight)

300

+ 0.0

2nd

Hydroxyapatite (MgO, 0.3% by weight)

500

-0.05

3rd

Hydroxyapatite (MgO, 0.3% by weight)

700

-0.2

4th

Hydroxyapatite (MgO, 0.3% by weight)

900

-0.6

5

Hydroxyapatite (MgO, 0.3% by weight)

1250

-10.0

6

Hydroxyapatite (MgO, 0.3% by weight)

1350

-20.0

7

Hydroxyapatite (MgO, 3.0% by weight)

300

+ 0.2

8th

Hydroxyapatite (MgO, 3.0% by weight)

500

-0.01

9

Hydroxyapatite (MgO, 3.0% by weight)

700

-0.1

10th

Hydroxyapatite (MgO, 3.0% by weight)

900

-0.4

11

Hydroxyapatite (MgO, 3.0% by weight)

1250

-6.0

12

Hydroxyapatite (MgO, 3.0% by weight)

1350

+ 0.1

Each of the powdery samples of hydroxylapatite shown in Table 2 was slurry-filled in an artificially formed defect in the femur of a rabbit (3 mm in diameter by 4 mm in length), and the postoperative course was observed after one month determine the formation of new bone and the compatibility with the living body.

65 Favorable results were found for compatibility with the living body, except for samples 1, 7 and 12. Particularly preferred results were found for the formation of new bone if

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powder samples No. 3,4, 5,10 and 11 were used, in which new bone tissue had grown to such an extent that it almost filled the central region of the defects.

Example 3

A hole with a diameter of 0.8 mm and a depth of 3 mm was surgically drilled in the tooth root canal of a dog and a cylinder or io column made of hydroxylapatite (calcined at 1250 ° C, content of inorganic metal ions: 0 , 1% by weight, calculated as MgO) with a zeta potential of - (minus) 3.4 mV according to the measurement with distilled water with the dimensions 0.9 mm in diameter x 10 mm L. At the same time, a piece of the same dog's neck bone was taken out, the piece of bone taken out having dimensions of 5 mm 2 and a height of 3 mm, and the cut-out part was made using an implant material in the form of a square truncated column with dimensions 2 mm fixed in a square and a height of 5 mm from the same hydroxyapatite.

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One month after the implantation operation, the areas filled with the hydroxyapatite implant material according to the invention were removed and observed in order to examine the tissue adjacent to the implant materials. The result showed that the interfaces and gaps between the implant materials and the living tissue in both operating areas were completely filled with newly grown bone tissue without a noticeable foreign body reaction, which showed a suitable and greatly improved compatibility with the living body.

Example 4

Glasses each containing calcium phosphate as the main ingredient and the other components shown in Table 3 below were made by melting at the temperatures shown in the table and then rapidly cooling to produce products in granular form. The grains were pulverized into a powder which was subjected to the test for determining the zeta potential in the same manner as in Example 1. Distilled water was used in each test.

Table 3

sample

Ca2 + / P043 "

CaO + P2O5

other ingredients

Enamel

Zeta pots

No.

(Atomic ratio)

(% By weight)

as CaO + P2O5

temperature (° C)

tial (mV)

1

0.1

5

Na20, Si02

750

+ 8.0

2nd

0.1

15

Na20, Si02

770

+3.2

3rd

0.1

80

Na20, Si02

850

+ 0.0

4th

0.2

5

Na20, Si02

780

+6.5

5

0.2

15

Na20, Si02

880

-10.6

6

0.2

80

Na20, Si02

950

-14.5

7

2.0

5

Al203, Si02

1710

+2.0

8th

2.0

15

Al203, Si02

1600

-0.05

9

2.0

80

Al203, Si02

1350

-3.1

Each of the glass powders listed in Table 3 was sieved and the fraction corresponding to a mesh size of 1.0 to 0.5 mm was filled in a bone defect (3 mm in diameter x 4 mm in length) which had been artificially formed in the thigh bone of a dog. The postoperative course was examined in each dog after four weeks.

As a result, it was found that no noticeable new bone formation between the glass particles was observed in the cases where the samples Nos. 1 to 4 and 7 were applied to-45, while a network of newly grown bone tissue between the glass particles in the cases was observed in which the samples other than Sample Nos. 1 to 4 and 7 were implanted. The network of newly grown bone tissue obtained by using Sample No. 9, which was most advantageous because it was dense and solid.

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Claims (4)

664 280 1. Inorganic implant material containing an inorganic material with a negative zeta potential. 2. The method for producing an inorganic implant material according to claim 1, characterized in that the inorganic material is obtained by calcining a starting material consisting of at least 90% by weight calcium phosphate compound and at most 10% by weight other inorganic metal ions at a temperature of not less than 500c becomes. 2nd PATENT CLAIMS 3. The method according to claim 2, characterized in that the inorganic material made of a glass with a molar ratio Ca2 + / P043 "in the range of 0.2 to 3.0 and a total content of CaO plus P205 of not less than 15 wt .-% is obtained. 4. The method according to claim 3, characterized in that the glass is formed by melting the starting material therefor at a temperature of 800 to 1700 ° C and that the content of inorganic oxides except CaO and P205 of this glass is less than 85 wt .-% .