CZ20003459A3 - Biologically degradable cement with enhanced properties - Google Patents

Abstract

Biodegradable cements especially mixtures of powders calcium phosphate with different stoichiometric composition improved properties. All mixtures contain tricalcium phosphate (TCP) and at least one other other phosphate containing an inorganic compound of different composition, while the TCP share has a well-defined division particle size

Description

Biodegradable cement with improved properties

Technical field

The invention relates to biodegradable calcium phosphate cements, in particular mixtures of powders containing calcium phosphate of different stoichiometric compositions having improved properties. The compositions of the invention each contain tricalcium phosphate (TCP) and one or more other inorganic, phosphate-containing compounds of different compositions, wherein tricalcium phosphate (TCP) is comprised in a well defined particle size range.

BACKGROUND OF THE INVENTION

The naturally occurring bone mass consists of calcium phosphate having a hydroxyapatite structure. However, the composition of bone minerals does not correspond to the ideal stoichiometric composition of crystalline hydroxyapatite (Ca 10 (PO 4) 6 (OH) 2), but generally has a non-stoichiometric composition due to the inclusion of other anions such as carbonate or hydrogenphosphate instead of orthophosphate but also other cations such as sodium , potassium or magnesium instead of calcium.

Biodegradable calcium phosphate cements (CaP) have an increasing interest in tramatology and orthopedics for the limited availability of autogenous bone and for biological problems with allogeneic bone. A drawback of many available calcium and phosphorus based bone substitutes is that they are essentially non-biodegradable.

For many years it has been possible to prepare a synthetic bone material based on hydroxyphosphate-like calcium phosphate compounds which, for its qualitative and structural properties, is capable of producing a bone material. · 2 · 2 · 2 · 2

time very similar to natural bones. Thus, the known disadvantages that occur in obtaining natural autogenous or heterogeneous bone can be avoided. Furthermore, the advantage of these materials is that they withstand mechanical stress in fact as well as natural bones, so that they can be used in the case of larger bone defects or bone fractures.

The major components of these materials are, for example, tricalcium phosphate (TCP), dicalcium phosphate (DCP) and tetrakalcium phosphate (TTCP), which in the presence of water react to obtain hydroxylapatite, which is the final product of the cementing reaction. Since hydroxyapatite is formed in this way in an aqueous environment, it resembles biological apatites much more than hydroxyapatite produced at high temperatures. Such cements are therefore osteotransductive and are therefore very suitable for bone repair and reconstruction. They rapidly integrate into bone structures and then translate into new bone tissue by the cellular activity of osteoblasts.

Depending on the conditions, the following solids may be in the system

Ca (OH) 2 - H 3 PO 4 - H 2 O

Ca (H ₂ PO 4) 2 -H ₂ O (MCPM) CaHPO ₄ (DCP) CaHPO ₄ · 2H ₂ O (DCPD) Ca ₈ (HPO ₄ ) 2 (PO 4) 4 · 5H ₂ O (OCP) Ca ₉ (HPO ₄ ) (PO ₄ ) ₅ OH (CDA) Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ (PHA) Ca ₃ (PO ₄ ) ₂ -H ₂ O (ACP) Ca ₃ (PO ₄ ) 2 (α, β-TCP)

Such cements are described, for example, in patents

US No. 4,518,430, US 4,612,053, US 4,678,355, US 4, , 880, 610, US 5,053,212, U.S. Pat 5,152,836, US 5,605,713, EP 0 416 761, EP No. 0 543 765, EP 0 664 133 a. W 0 96/36562.

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Furthermore, a prior art cement comprising cf-TCP and (3-TCP and a small amount serving as a crystallization core, precipitated hydroxylapatite (PHA), whose solidification behavior has been investigated) is known (Jansen et al., J. Mat. Sc.: Mat, Med. 6: 653-657 (1995). The general reaction of α-TCP with water is as follows:

3a-Ca ₃ (PO _{4) 2} + H ₂ 0 -> Ca ₉ (HPO ₄₎ (P0 _4), and the reaction with 0H dikalciumfosfátern is as follows:

2CaHPO ₄ + 2a-Ca ₃ (PO ₄ ) ₂ + 5 H ₂ 0-> Ca ₈ (HPO ₄ ) 2 (PO ₄ ) ₄ · 5H ₂ O.

The hardening of the initial pasty mixture is achieved by the blending of calcium-deficient hydroxylapatite crystals precipitated during solidification ί,

The properties of the known hydroxyapatite or calcium phosphate cements, especially their physiological acceptability, the required bioabsorbability and the ability to replace or regenerate newly generated natural bone tissue, and some physical properties, such as compressive strength and hardening time, depend on more or less pronounced crystal ini the particle size and porosity that can be achieved during preparation.

Therefore, various biocements are obtained, for example, by adding monohydrogen calcium phosphate or calcium carbonate or monohydrogen calcium phosphate together with calcium carbonate to a mixture of α-TCP and (3-TCP (Khairoun et al., Biomaterials, 10, 1535-1539, 1997)). which are obtained after curing is in the 30 MPa range and thus in the trabecular human bone field (Driessens et al., Bioceramics 10, 279-282, 1997) but achieving these high compressive strength values takes 15 to 30 hours in spite of use of common hardening accelerators, which is too long for use in trauma • · φφ φφ φ φ φ φ φφ φφ

- ζΐ - - ologii φ φ ologii ologii ologii ologii ologii ologii ologii ologii ologii ologii ologii ologii in orthology and orthopedics for early stability and loading. In these cases, the οί, β-TCP mixture is ground together until 60 to 70% of the powder has a particle size of less than 8 µm and the rest of the particles have a size of less than about 35 µm.

It is therefore of constant interest to develop bone cements that have different properties to meet different requirements. The invention relates to such cements having special properties. In particular, the problem solved by the invention is whether new cements with improved properties can be obtained by varying the grinding of the particles of the TCP mixture together with the admixtures of other inorganic phosphorus compounds.

SUMMARY OF THE INVENTION

A blend of powders suitable for the preparation of absorbable calcium phosphate cements containing tricalcium phosphate (TCP) and at least one other other phosphate containing an inorganic compound. according to the invention, the tricalcium phosphate particles have the following particle size distribution up to 90% · 0.1 to 40 µm to 70% · 40 to 300 µm.

This means that the essence of the invention is that a certain proportion of fine particles (about 1 to 40 µm) and very fine particles (about 0.1 to 1 µm) be included for a certain proportion of coarse particles (40 to 300 µm) )

The composition of the invention must always contain tricalcium phosphate (TCP). Tricalcium phosphate is mainly found in two crystalline modifications, a and β. According to the invention, the mixture comprises oe-TCP with a possible admixture of up to 60% β-TCP. The invention relates to a composition in which 40 to 100% by weight of tricalcium phosphate is present in the form (β-TCP) and 0 to 60% of tricalcium phosphate is present in the β form (β-TCP). TCP stands for a- and β-TCP mixture.

9β

In particular, according to the invention, 30 to 70% of the TCP particles have a particle size of 10 to 100 µm. The following TCP size distributions are particularly preferred

0, 1 up to 7 µm. Invention more · 60 % of particles TCP ve 1 i bone j is a mixture of i, which have us part i c: 30 up to 50%: 1 to 7 pra 20 May up to 40%: to 40 um. 10 up to 50% = 40 to 100 ALIGN! pra. She found out se, that not only

The particle size has a beneficial effect, but also in the mixture also the importance of the size and properties of the remaining phosphate-containing compounds. According to the invention, at least 50% of these non-TCP particles should be 10 to 100 parts in size. Generally, these particles should be ground so that they are neither too fine nor too coarse. The proportion of these nonTCP compounds in the composition according to the invention is 1 to 85%, in particular 5 to 60%.

Suitable compounds that can be located with TCP are generally all inorganic compounds that contain calcium and phosphate. Particularly suitable such compounds are disclosed in EP 543765. Preferred are compounds selected from the group consisting of:

Ca (H ₂ PO 4> .HaO, CaHPO ₄ , CaHPO ₄ .2H ₃ 0, Cas (HPO ₄ ) 2 (PO ₄ ) ₄ .5H ₃ 0,

Cag (HP0 ₄₎ (P0 ₄₎ SOH Caio (P0 ₄₎ 6 (OH) 2, containing a carbonate apatite, CaC0 _3, Ca (0H) s, MgHP0 .3H20 _4, Mg ₃ (P0 ₄₎ 2, ₄ CaNaP0 ,

CaiiNa (P0 ₄₎ 2, CaKP0 ₄ Ca2P0 ₄ Cl, Ca NaK ₃ (P0 _{4) 2,} Ca (P0 _{4) 6} C1 _{3, 4} ZnHP0 .4Hs0 and Zn ₃ (P0 _{4) 2} and in particular from the group consisting of

Cas (HPO ₄ ) ₃ (PO ₄ ) ₄ .5H ₃ 0, Ca ₁₀ (PO ₄ ) & (OH) 2, CaHPO ₄ and CaCO ₃ .

Particularly suitable are mixtures of the following composition by weight:

marriage: and) TCP: 90 to 99% Caio (P0 ₄ ) & (OH) 2 ^: 1 to 10 (i) TCP: 90 to 99% Cas (HP0 ₄ ) ₄ (P0 ₄ ) ₄ , .5H2O: 1 to 10

• · ·

(iii) TCP: 70 up to 99% Caio (P0 ₄ ) © (OH) and: 1 to 10 Λ CaC0 ₃ : 10 to 20 % ·, i (v) TCP: 70 up to 99% Cas (HP0 ₄ ) 4 (P0 ₄ ) 4 .5H ₂ 0: 1 aš 10% ·, CaC0 ₃ : 10 to 20 % ‘, in) TCP: 40 up to 99% Caio <P0 ₄₎ 6 (OH) ^3: 1 to 10 CaHPO-4: 1 to 50 % \ (vi) TCP: 40 up to 99% Cas (HP0 ₄ ) 4 (P0 ₄ ) ₄ .5H ₂ 0: 1 as 10%; CaHP0 ₄ : 1 to 50 %; (vii) TCP: 20 up to 99% Caw (P ₄ ) 6 (0H) 3: 1 to 10 CaHPO-4 ^: 1 to 50 %; CaCO ₃ : 1 to 20: (viii) TCP: 20 up to 99% Cas (HP0 ₄ ) 4 (P0 ₄ ) ₄ . 5H ₂ 0: 1 aš 10%; CaHP0 ₄ ^: 1 to 50 %, CaCO ₃ : 1 to 20: %.

The compositions according to the invention may optionally contain additional hardening accelerators. A suitable curing accelerator is disodium hydrogen phosphate.

It has also been found that the biocement-containing tricalcium phosphate according to the invention is particularly advantageous when the weight content of magnesium and sodium in the starting compounds is not higher than 0.13% magnesium and 0.2% sodium.

The implantation of biomaterials into the human and animal body is associated with the risk that germs will multiply on these inanimate materials because these materials initially do not have a vascular supply and therefore cannot be protected by the immune system. It is therefore desirable to add antibiotics, for example from aminoglycosides such as gentamicin or cefazoline, clindalaycin palmitate, and in particular clindamycin phosphate or disinfectants, to the biomaterials for their own temporary protection against germs during implantation. However, it should be considered that antibiotics and / or disinfectants are not only incorporated into cements, but also leached out of them. Antibiotics and / or disinfectants must not adversely affect mechanical or processing properties.

99

9 9 9

9 9 · · · ···

99

99 9 9 9

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9 9 9 · 9 cements, eg curing time, in accordance with intended use. Suitable disinfectants are acridines, in particular biguanidines, such as chlorhexidine, and polyhexanide (Lavasept ^R ) is particularly preferred. In addition, incorporation of the antibiotic and / or disinfectant into the absorption-capable calcium phosphate cements and the gradual leaching of the antibiotic and / or disinfectant from the absorption-capable calcium phosphate cements allows implantation into areas at risk of infection after surgical removal of foreign bodies and inanimate tissue from the wound. In addition, osteomyelitis treatment, characterized by chronic infection and osteonecrosis, is facilitated since osteomyelitis can be treated in a single operation.

In addition, it is desirable to mix other pharmaceutically active substances having a very broad field of action with the absorption-capable cements, for example increasing the cellular activity of the bone surrounding the cement to achieve increased absorption of cement and its replacement by endogenous bones. in the sense of chemotherapy, which prevents the release of the stabilizing cement filler after tumor resection by tumor leakage left in the eye1.

Examples of such preferred active ingredients are growth factors such as FGF (fibroblast growth factor), BMP (bone morphogenetic protein) or TGF-β (tissue growth factor) or other active ingredients such as prostaglandins or agents that affect prostaglandin metabolism , active substances that interact with the metabolism of the thyroid or pithyroid glands, or even chemotherapeutic agents such as methotrexate. It has now been found that the admixture of such substances leads to corresponding hardened biocements for their structure which is capable of releasing these active substances into the environment within a short time or several

• φ φ

Φ Φ »· dní dní dní dní dní dní φ φ · · · · φ · · · · · · dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní dní

The invention therefore also relates to compositions which additionally contain one or more pharmaceutically active substances or one or more disinfectants.

For implantation or injection, the compositions of the invention must be mixed with an aqueous liquid such that the solidification or formation of apatite structures or apatite-like materials proceed according to the equation set forth in the introduction. As a result, advantageous properties are obtained by mixing the powder mixture with an aqueous liquid. The paste obtained after mixing the solid and liquid phases has, depending on the temperature, some processing possibilities such as modeling and the suitability for injection at certain time intervals. Suitable aqueous liquids are, for example, physiological saline solution, body fluids such as blood or serum, or aqueous buffers. In principle, components such as pharmacologically active ingredients or curing accelerators can be mixed not only with TCP powder, but also added as an aqueous solution to the blended biocement. The product then takes the form of a creamy suspension or paste which can be easily incorporated into the destination or into defective bone structures.

The invention therefore also relates to a corresponding composition, paste or suspension and its use for the production of biodegradable implantable synthetic bone materials.

The mixed and solidifying compositions according to the invention are distinguished in particular according to the required compressive strength of 30 MPa or more, which is achieved depending on the composition of the composition according to the invention after only very short curing times of 2 to 10, preferably 3 to 6 hours. in the case of mixtures having a slightly changed composition, as a rule, the curing times are 15 to 30 hours and the strength is only slightly above 30 MPa. With these long curing times, it is possible to achieve at φ φ • φ φφφ φ •

φ * 0 «p p p p p p p p p p p p p p p p p p p p p p p p p p p The invention has a compressive strength of 40 to 50 MPa.

The invention is illustrated, but not limited, by the following examples and the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1: Antibiotic extract from biocement D

Batch:

I. 1 g cement + 0.7 ml Refobacin 120: 0.7 g / 20 ml buffer (= 20 mg)

II. 1 ml Med. 5-agar + 0.7 ml Refobacin 120/20 ml buffer

III. 1 g cement + 0.7 ml cefazoline 60 mg / ml, 1.04 / 20 ml buffer (= 25.7 mg)

IV. 1 g cement + 0,7 ml netiymycin 60 mg / ml, 1,15 g / 20 ml buffer <= 28,4 mg)

V. 1 g cement + 0,7 ml clindaraycin phosphate 60 mg / ml,

0.99 g / 20 ml buffer (= 24.5 mg)

Leach in 1/15 M phosphate buffer, pH 7,4, 37 ° C

The designation [sic] I to V corresponds to the identical designation of the curves in FIG.

In Fig. 1, the x-axis shows the time (in hours) and the y-axis the concentration in (µg / ml).

Giant. 2 = Release of gentamicin from cement Η, B, F and D (in µg)

The x-axis shows the time (in days) and the y-axis shows the release (in yg).

The mixture numbers in the following table correspond to the identically marked curves.

• 9 • 9 • 9 • 9

9,999 999,999 99 · • ·· · · ····

Mixture 1 2 3 4 Cement H (B) F D Buffer 20 May 20 May 20 May 20 May Gentamicin in% 4.2 4.2 4.2 4.2 Set Na ₂ HPO ₄ Na ₂ HPO ₄ Na ₂ HPO ₄ Na ₂ HPO ₄ den 1 249.13 308.28 238j91 302.06 den 2 18.93 21.35 29.55 22 _; 16 den 3 7.05 8.96 12.30 14.02 den 4 6.63 7j20 9, 05 12.64 den 5 3.91 4.14 6.44 9.44 den 6 4.05 4.07 5.15 7.95 den 7 2.53 3.57 5.13 6 _; 71 den θ 1.83 2.96 2, 55 3.74 den 9 1.39 3.75 2.96 4.55 den 10 1.86 3.20 2.75 3.99 Total 290.37 367.47 314.78 387.27

DETAILED DESCRIPTION OF THE INVENTION

Example 1 o

They are prepared by ct-TCP calcination at 1350 ° C for 4 hours followed by cooling in room air with 2 molar mixtures of 2 · 1 calcium hydrogen phosphate and calcium carbonate. The reaction product obtained contains less than 10% β-TCP.

The .alpha.-TCP is ground, sieved, and mixed so that about 50% of the particles have a particle size of 0.1 to 7 µm, about 25% of the particles have a size of 7 to 25 µm, and another 25% of the particles have a size of 25 to 50 µm. OCPs were prepared as described by LeGeros (Calcif. Tiss. Int. 37: 194-197 (1985)).

By way of example, the properties of the following cementitious compositions are given, the marks having the following meaning ^:

- 11 - • · • · · • · • · • · · · • · · · · · · · · · · · · · · · • · · · · · · ··· · · · · · · • · · · · ·· · · ·· · · B i ocement H: mixture c-TCP and PHA B i ocement F: mixture c-TCP DCP and PHA B i ocement D · ' mixture c-TCP DCP, CaCO ₃ and PHA B i ocement H-OCP: smšs cf-TCP and OCP B i ocement F-OCP: mixture three-TCP, DCP and OCP B i ocement D-OCP: mixture c-TCP DCP, CaCO ₃ and OCP Biocement a-TCP DCP CHCO3 PHA OCP a-TCP 20 May - - - - H 20 May - - 0.40 - H-OCP 20 May - - - 1.00 F 14 ’6.0 - 0.40 - F-OCP 14 6.0 - - .1,00 D 14 6.0 2.0 0.40 - D-OCP 14 6 _; 0 2.0 - 1, 00 Numeric Values a mixed ratios are in grams. Ka- used fuel to be mixed of pills is 4% solution hydrogen phosphate in  water !. Liquid to liquid ratio powder is 0.30 ml / g powder, Onset of setting (ti) a time to achieve complete hardening (tf) with z they are protecting ex room temperature (20 + O 1 C) and at

temperature of 37 ± 1 C by the ASTM method using Gilmoore needles.

Compressive strength is determined by a Lloyd LR50K type machine after immersion in Ringer's solution for 1, 2, 4, 18 and 65 hours. The reaction product is determined by X-ray diffraction.

K. The preparation of F, F-OCP, D and D-OCP bio-cements, whose common feature is the admixture of DCP, is a particularly preferred DCP whose Ca / P ratio is greater than 1.45.

• ·

Example 2

Antibiotic / disinfectant active in liquid and solid form are admixed to the cured cements and the release behavior is determined. The elution solution used is a phosphate buffer according to Sorensen, having a pH of 7.4 at 37 ° C.

Curing properties of cement mixtures with antibiotics / disinfectants are determined according to ASTM standards.

X-ray diffractographic measurements indicate that the calcium hydrogen phosphate in cements F-OCP and D-OCP does not react and, despite the addition of OCP as the crystallization nucleus, produces calcium-deficient hydroxyapatite.

□ o

Cure times (min) such as ti and tf at 20 C and 37 C (standard deviation)

Biocement ti (15 ° C) ti (36 ° C) tf (15 ° C) t _f (36 ° C) a-TCP 31 (1) 5 (0.25) 51 (1) 7 (0.5) H 19 Dec (1) 3, 25 (0.25) 40 (1) 6 (0.5) H-OCP 17 .5 (1) ³ ) 25 (0.25) 35 (1) 6 (0.5) F 5. 75 (0.25) ³ ; 25 (0.25) 16 (1) 9 (1 _; 5) F-OCP 10 (0,5) 3, 5 (0.25) 16. 5 (2) 4.5 (0.25) D ⁹ ? 75 (0.5) ³ , 5 (0.25) 19 Dec (1) 8.25 (0.5) D-OCP 11 , 5 (0.5) 3 (0 _; 25) 22nd (1) 6.5 (0 ^ 5)

· · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

Compressive strength after 1, 2, 4, 18 and 65 hours

Biocement 1 h 2 h 4: h 18 h 65 h a-TCP 10 mm (1) 18 31 (2) - 32 (3) H 11 (D 20 May (1) (2) 40 (4) 41 (5) H-OCP 13 mm (1) 18 (2) (3) 40 (5) - F 11 (2) 18 (3) (3) 31 (4) 39 (2) F-OCP 11 (2) 29 (1) (2) 42 (3) 41 (2) D 10 mm (2) 16 26 (2) 45 (5) 47 (2) D-OCP 10 mm (1) 16 23 (1) 45 (3) 47 (6) The results show that is achieved object of the invention. By adding OCP and PHA is the time beginning and ends hardening shortened abutment i

α-TCP (with 10% ρ-TCP content). The shift in curing kinetics to shorter times is particularly pronounced at low temperature, while at body temperature the effect is only very weak. This is particularly advantageous for the processing properties of the cement obtained, since a sufficiently long processing time at room temperature is guaranteed, while curing at body temperature is not too short, so that the cement introduced can still be modeled. Exemplary compressive strength data of biocement show that the final strength is generally reached after 6 hours, and that the biocement t> and D-OCP achieve a strength of up to 50 MPa.

Example 3

In this example, it is shown that a further object of the invention is achieved, namely mixing and progressive release of active substances from cements, for example antibiotics, to protect the implant and prevent infection.

Exemplary release kinetics of biocement D containing different antibiotics as well as the release kinetics of different gentamicin-containing biocements are shown in Figures 1 and 2.

By admixing antibiotics / disinfectants, the hardening kinetics or strength are not adversely affected with respect to the desired antibiotic release effect. Exemplary biocement results of H, F, and D with gentamicin sulfate powder in a liquid to powder ratio of 0.30 using disodium hydrogen phosphate solution or gentamicin sulfate solution as the

at a temperature of 37 [deg.] C. The stated strength values were determined after 20 hours. The values of tj and tf are measured in minutes and relate to measurements with a Gilmoore needle. Cohesion time (CT) is measured at room temperature and is given in minutes.

Measured values using gentamicin sulfate powder 120 mg / 5 g cement

Biocement ti t <CT F (MPa) without gentamycin ti t _£ CT F (MPa) with gentamycin

H 3.5 6 6 40 + 4 8 14 1.5 37 + 3 F 3.5 5 b ⁵ 31 + 4 b ⁵ b ⁵ 1.5 39 + 3 D 4 5.5 b ⁵ 45 + 5 5 8 b ⁵ 41 + 1 Measured values ex use i t i gentamicin sulfate as rostoku (Refobacin 120 ^R , without use i t i d. Sodium hydrogenphosphate and pouse

with calcium hydrogen phosphate

Biocement ti t _f CT F (MPa) ti tf CT F (MPa) Refobacin 120® Na ₂ HP0 ₄ H 7 12 <2 48 + 4 b ⁵ 6 6 40 + 4 F 3,5 5 3.5 31 + 4 b ⁵ b 5 1,5 39 ± 3 D 4 5,5 b ⁵ 45 ± 5 5 8 b ⁵ 41 + 1

• · · · · · · · · · · · · ·

Φ Φ Φ Φ Φ

Example 4

Preparing TCP with default materials

In the preparation of TCP, the percentage of α and / (3 TCP is significantly influenced by the weight percentage of magnesium and sodium in the starting materials, but also by the ratio of calcium to phosphorus.

% Mg %On % β- 0.11 0.12 5 0.39 0.10 70 0.25 0,022 35 0.23 0, 025 25 <0.0005 0,0024 <5 <0.0005 0,0029 <5 <0.0005 0,0013 <5 0,062 0081 <5 0.11 0.72 100 ALIGN! 0,0024 0.20 <5 0.13 0.20 <5

Industrial applicability

Mixture of powders suitable for the preparation of absorbable biodegradable calcium phosphate cements containing tricalcium phosphate and at least one other other phosphate containing an inorganic compound for the production of a biodegradable synthetic bone material implant.

Claims (14)

PATENT CLAIMS A mixture of powders suitable for the preparation of absorbable calcium phosphate cements containing tricalcium phosphate (TCP) and at least one other other phosphate containing an inorganic compound, characterized in that the tricalcium phosphate particles have the following particle size distribution 30 to 90%: 0.1 to 40 μ® 10 to 70% 40 to 300 µm. Powder mixture according to claim 1, characterized in that 30 to 70% of the tricalcium phosphate particles have a particle size of 0.1 to 7 µm. Powder mixture according to claim 1, characterized in that at least 10 to 60% of the tricalcium phosphate particles have a size of 40 to 100 µm. Powder mixture according to claim 1, characterized in that the tricalcium phosphate particles have the following particle size distribution 30 to 50%  1 to 7 jum 20 May to 40% : 7 to 40 / jm 10 to 50% : 40 to 100 ALIGN! jum Powder mixture according to claims 1 to 4, characterized in that at least 50% of the remaining tricalcium phosphate particles have a size of 10 to 100 μα. Powder mixture according to Claim 1 to 5, characterized in that 40 to 100% of tricalcium phosphate is present in the form (α-TCP) and 0 to 60% of the tricalcium phosphate is present in the form (β-3). TCP). 7. Powder mixture according to claims 1 to 6, characterized in that 99 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 99,999 999,999 99 9 9 9 9 9 9 9 9 9 9 9, characterized in that it contains from 1 to 85% by weight of other phosphate-containing compounds, based on the mixture as a whole. Powder mixture according to claims 1 to 7, characterized in that at least one other phosphate-containing compound is selected from the group consisting of: Ca (H ₂ PO ₄ ). H ₂ 0, CaHPO ₄ , CaHPO ₄ .2H ₂ 0, Cas (HPChi) z <PCU) ₄ .5H ₂ 0, Cas (HPO4) (PO4) sOH, Caiq (PO4) 6 (OH) 3, apatite-containing carbonate, CaCO 3, Ca (OH) ₂ , MgHPO ₄ .3H ₂ O, Mg 3 (PO 4) 2, CaNaPO ₄ , CaiiNa (P0 ₄₎ 2, CaKPO _4, Ca ₂ PO ₄ Cl, Ca ₂ NaK (P0 ₄₎ 2, Ca 10 (P0 ₄₎ & C12 ZnHPO ₄ .4H ₂ 0 and Zn ₃ (P0 ₄₎ 2 and in particular from file including Cas (HPO4) 3 (PO4) 4 · 5H.20, Ca 10 (PO ₄ ) 6 (OH) 2, CaHPO ₄ and CaCO ₃ . Powder mixture according to claim 8, characterized in that at least one other phosphate-containing compound is selected from the group consisting of: Time (HPO4) 2 (PO4) 45H ₂ 0, Caio (PO4) and (OH) 2, CaHPO ₄ and CaCO. 10. Powder mixture according to claim 9 load ! AT her c í t í m that blend as the whole has this mass Ingredients and) TCP: 90 to 99% Caio (PO4) 6 (OH) 2 ^: 1 to 10 y (i) TCP: 90 to 99% Time (HPO4) 2 <PO4) 4. .5H ₂ 0, : 1 to 10 (iii) TCP: 70 to 99% CaCO ₃ : 10 to 20 Caio (P0 ₄ ) 6 (0H) ₂ : 1 to 10 % i (v) TCP: 70 to 99% CaCO ₃ ^: 10 to 20 Cas (HPO4) 2 (PO4) 5. %; .5H ₃ 0, : 1 to 10 in) TCP: 40 to 99% CaHPO4: 1-50 Ca 10 (PO ₄ ) 6 (OH) 2%; 1 to 10 % (i) TCP · 40 to 99% CaHPO ₄ : 1 to 50 Cas (HPO4) 2 (PO4) 5 % ·, 5H2O, : 1 to 10 (vii) TCP: 20 to 99% CaHPO ₄ = 1 to 50 Ca 10 (PO 4) 6 (OH) 2 = Z; CaCO ₃ ^: 1 to 20 5% 1 to F 10 Λ » viii) TCP: 20 to 99% Cas (HP0 ₄ ) 2 <P0 ₄ ) 4.5H ₂ 0, = i to 10 Sí; CaHPO ₄ ^: 1 to 50%, CaCO ₃ ^: 1 to 20%. • φ φ φ φ φ • φ φ φ Powder mixture according to Claims 1 to 10, characterized in that the mass content of magnesium and sodium in the starting compounds is not higher than 0.13% magnesium and 0.2% sodium. 12. Mixture of powders according to of claim 1 s e by containing when long ago 13, Mixture of powders according to of claim 1 s e by including long ago to 11, characterized by a solidification accelerator. to 12, characterized by a pharmaceutically active substance. 14. se t 1átek. Powder mixture according to claim 13, characterized in that it contains antibiotics or disinfectants Powder mixture according to one of Claims 1 to 14, characterized in that it is in the form of a solution, a suspension or a paste. 16. A biodegradable implant, characterized in that it is made from the cured composition of claim 15. Use of the composition of claim 15 for the manufacture of a biodegradable synthetic bone material implant.