JP2001518359A - Surgical hydraulic cement - Google Patents

Abstract

(57) [Summary] Surgical cement contains three components. The first component is beta tricalcium phosphate β-Ca ₃ (PO ₄ ) ₂ (β-TCP) particles; and monocalcium phosphate Ca (H ₂ PO ₄ ) ₂ (MCPA) particles or monocalcium phosphate monohydrate Containing Ca (H ₂ PO ₄ ) .H ₂ O (MCPM) particles or phosphoric acid. The second component contains water. The third component includes particles having an average diameter greater than the average diameter of the beta tricalcium phosphate β-Ca ₃ (PO ₄ ) ₂ (β-TCP) particles of the first component. Wherein upon mixing the three components, hardened mass containing brushite _{CaHPO 4 · 2H 2 O (DCPD} ) is formed. The β-TCP particles have a specific surface area of less than 10 m ² / g and a Ca / P atomic ratio different from 1.50. This component comprises 1 to 99 volume percent of the cured mass. The cements according to the invention can be used for dental and maxillofacial surgery (remodeling of alveolar ridges, filling tooth cavities), orthopedic applications (fracture repair, bone augmentation) and topical drug delivery applications (antibiotics, Anti-inflammatory drugs and anti-cancer drugs).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[Field of the Invention]

The present invention relates to a surgical cement according to the preamble of claim 1, a method for producing brushite as a temporary bone substitute according to the preamble of claim 34, and claim 35.
The present invention relates to a temporary bone substitute obtained by the above method.

[0002]

[Problems to be solved by the invention]

Many such hydraulic cements based on calcium phosphate for use in surgery are known in the prior art; these cements mix the two components (powder / liquid) intraoperatively, and the two components harden in situ. It is prepared by applying the two components in a paste-like consistency to a suitable location. The disadvantages of prior art hydraulic cements based on calcium phosphate are:

[0003] Short curing times that are not practical and cannot be used for elaborate surgical procedures; poor injectability, ie fresh cement paste tends to clog the injection needle, And / or degrades on contact with physiological fluids, which hinders the implantation of cement with minimal invasive surgical procedures; low-compacity, that is, current hydraulic cement, To be able to pour or to give the cement a convenient setting time, a larger amount of mixed water is required, which, after setting, results in a very low maximum mechanical strength.

In US-A-4 880 610, CONSTANTZ discloses a method for producing calcium phosphate mineral compositions in situ by combining phosphoric anhydride crystals with a calcium source leading to hydroxyapatite. . Obviously, the use of 100% phosphoric acid in the operating room and the application of a paste containing 100% phosphoric acid to the human body must clearly be considered a non-ideal treatment requiring improvement. Furthermore, the hydroxyapatite materials produced by this known method have a long resorption period, which is not proportional to the rate of bone regeneration. The disadvantage of this long resorption period is that bone treated with cement remains in abnormal biomechanical conditions for long periods of time, which may cause secondary post-operative problems. In addition, cement that is not resorbed will still break into pieces and debris after prolonged mechanical loading. This increases the likelihood of post-operative complications, a sterile inflammatory response. The ideal cement resorption rate should be as close as possible to the natural rate of new bone formation, which is about 20 micrometers (μm) per day.

[0005] A calcium phosphate composition using alpha TCP particles is known from GB-2 260 977 of MITSUBISHI. Alpha TCP particles are more reactive than beta TCP particles, and thus, when mixed with monocalcium phosphate monohydrate and water, the curing time is too fast (2,3 seconds) and therefore Difficult to control.

[0006] MIRCHI AA ET AL, described in Biomaterial 1989, Vol. 10, No. 9, November 1, 1989, pp. 634-638.
.), Calcium phosphate cements are commercially available with MCPM and Ca
It is known to have β-TCP particles with a / P ratio of 1.50. The disadvantage of β-TCP particles having a Ca / P ratio of 1.50 is their relatively high reactivity, which makes them unsuitable as surgical cement.

[0007]

[Means for Solving the Problems]

The claimed invention aims to solve the above-mentioned problems. The present invention relates to claim 1.
And a method for producing a temporary bone substitute material according to claim 34 and a temporary bone substitute material according to claim 35.

The various features of novelty which characterize the invention are pointed out with particularity in the appended claims and the forming part of this disclosure. For a better understanding of the invention, its surgical advantages, and the particular objects achieved by its use, reference should be made to the appended examples in which preferred embodiments of the invention are described. It is described in detail.

[0009] The first component of the cement according to the present invention is beta-tricalcium phosphate β-Ca ₃
In addition to the (PO ₄ ) ₂ (β-TCP) particles, the following substances: a) Monocalcium phosphate Ca (H ₂ PO ₄ ) ₂ (MCPA) particles; or b) Monocalcium phosphate monohydrate Ca (H ₂ PO ₄ ) ₂ · H ₂ O (MCPM)
C) or phosphoric acid. Either a) or b) is preferred; phosphoric acid can be used in either solid or liquid form.

[0010]

BEST MODE FOR CARRYING OUT THE INVENTION

The Ca / P atomic ratio of the β-TCP particles of the first component is preferably from 1.35 to 1.4.
Included between 99. This ratio is between 1.45 and 1.47, typically 1.455
Significantly, it is included between １1.465. The advantage of the Ca / P atomic ratio used in the present invention is the low reactivity of the β-TCP particles. Low Ca / P atomic ratios-less than 1.5-can be achieved in a variety of ways. One possibility is the calcination and sintering of a DCP [CaHPO ₄ ] / hydroxyapatite [Ca ₅ (PO ₄ ) ₃ OH] mixture.

The Ca / P ratio is then adjusted by the ratio of the two components. Exactly 1.50 Ca
To obtain a / P ratio, 10 g of DCP should be mixed with 36.91 g of HA. To obtain a Ca / P ratio of 1.35, 10 g of DCP must be mixed with 13.6 g of HA. DCP is DCPD (CaHPO ₄ .H ₂ O),
_{MCPM [Ca (H 2 PO 4} ) 2 · H 2 O], can be replaced by _{CaPP (Ca 2 P 2 O 7} ) or _{OCP [Ca 8 (H 2 PO} 4) 6 · 5H 2 O].

Beta-TCP particles with a Ca / P ratio below 1.50 also have low DCP
, DCPD, MCPM or OCP is added to pure beta TCP powder, and then mixed to sinter the mixture and homogenize the mixture.

Another method is to add a small amount of Na ₄ P ₂ O ₇ .10H ₂ O (NaPPH) to β-TCP particles, which delay their dissolution in a synergistic manner. As a result, the setting time of the hydraulic cement is significantly increased. The presence of small amounts of CaPPH also indicates that β-T
It increases the sintering capacity of the CP particles, thus enabling the production of dense β-TCP particles. Non-thick β-TCP particles absorb the mixed liquid during curing. More mixed liquid must be used to knead the cement, as follows, reducing the mechanical properties of the cement after hardening. If the amount of CaPPH is too high (Ca / P ratio is 1.
(Less than 35), the mechanical properties of the cement are drastically reduced.

The average specific surface area of the β-TCP particles must be less than 10 m ² / g, otherwise the mechanical properties of the cement will be insufficient-due to the large porosity resulting from the large volume of the mixed liquid- The cement will have a setting time that is too short for practical purposes.

The setting time of the cement according to the invention, measured at 25 ° C., should be at least 2 minutes, typically at least 3 minutes, preferably at least 5 minutes.

According to a preferred embodiment of the present invention, the first component is divided into two sub-components A and B, sub-component A comprising MCPA and / or MCPM particles and sub-component B comprising β-T
Contains CP particles and a curing speed regulator.

The second component comprises water and additionally orthophosphoric acid (OPA) and / or sulfuric acid (
SA), which may also serve as cure rate modifiers, leading to an improved microstructure of the final brushite (DCPD) crystals.

After mixing of the three components, a hardened mass is formed containing the brushite CaHPO ₄ .2H ₂ O (DCPD), which, due to its solubility, has a slower resorption rate compared to HA. Used.

The total weight W _TCP of the first and third component β-TCP particles is preferably stoichiometric weight W _T = W _MCPA /0.7546+W _MCPM /0.8127+W _OPA /0.31
59 + W _SA /0.3162 is a should than be large, wherein, W _MCPA, W _{MC PM,} respectively W _OPA and W _SA, MCPA using, MCPM, OPA and S
A is the weight. Furthermore the weight W _TCP should be in the range of _{1.2W T ≦ W TCP ≦ 2.0W T} .

The first component further comprises sodium pyrophosphate, potassium pyrophosphate, sodium acetate
, Potassium acetate, sodium citrate, potassium citrate, lintoic acid
Lium (sodium phosphocitrate), Potassium phosphocitrate (potassium phosphoci
trate), sodium or potassium sulfate, calcium sulfate hemihydrate CaSO _Four ・ 0.5H_Two O (CSH), sodium pyrophosphate Na_Four P_Two O₇ ・ 10H_Two 
O (NaPPH), sodium dihydrogen pyrophosphate Na_Two H_Two P_Two O₇ (NaHP
P), calcium pyrophosphate Ca_Four P_Two O₇ (CaPP), magnesium sulfate and
And sodium diphosphonate or potassium diphosphonate.
The composition may include a chemical conversion regulator.

In a further preferred embodiment of the present invention, the particles having an average diameter larger than the average diameter of the beta-calcium phosphate β-Ca ₃ (PO ₄ ) ₂ (β-TCP) particles of the first component. Is added. This leads to an agglomerate structure of the final hardened cement, whereby the third component particles are embedded in the brushite matrix formed in the hardening process. The average particle diameter of the third component is at least twice, preferably at least 10 times larger than the average diameter of the first component beta-tricalcium phosphate β-Ca ₃ (PO ₄ ) ₂ (β-TCP) particles. Should be. Preferably the average particle diameter of the third component should be in the range of 50-2000 μm. The particles of the third component can consist of hydroxyapatite particles or polymer particles such as lactide, polysaccharide, collagen or protein.

In a further preferred embodiment of the invention, two different types of β-TCP particles are used, wherein the first type has less than 10% by volume of the particles being less than 1 μm, 5 μm
The second type is particles having an average diameter in the range of 150-400 μm, preferably in the range of 250-350 μm. The average particle diameter of the third component should be in the range of 50-2000 μm, preferably 2
It should be between 50 μm and 750 μm.

The volume V _L of the second component is preferably _{equal to} the volume V _T of the first component = (W _MCPA × 0.61
5 + W _MCPM × 0.5 + W _OPA × 1.102 + W _SA × 1.101) should be equal to or greater than ml / g. The volume _VL is typically 0.5
Range of _{V T ≦ V L ≦ 10.0V T} , preferably _{1.2 ≦ V T ≦ V L ≦} 2.0V T
Range.

One of the two components may further include a biodegradable polymer that controls the consistency of the cement paste resulting from mixing the two components, and the aggregation of the components in physiological fluids. it can.

The biodegradable polymer is a polysaccharide derivative, preferably hyaluronic acid, dextran,
Hydroxypropyl methylcellulose; chitin derivative, preferably chitosan; xanthan gum; agarose; polyethylene glycol (PEG); polyhydroxyethylene methacrylate (HEMA), synthetic protein and natural protein or collagen.

The first component may further comprise a pharmaceutically or physiologically active substance, preferably selected from the group of antibiotics, anti-inflammatory drugs, anti-cancer drugs and bone growth factors. The antibiotic is preferably gentamicin or a gentamicin salt, typically gentamicin sulfate. Other gentamicin salts also have a solubility of 1
It can be used as long as it is in the range of 00 to 2500 mg / l.

Antibiotics include aminoglycosides, vancomycins, gentamicins or salts thereof, preferably gentamicin sulfate or gentamicin clovefat
(gentamycin crobefat).

The cement according to the present invention may be used as a bone substitute in oral surgery (dental) and maxillofacial surgery (remodeling of alveolar ridges, filling tooth cavities), or for orthopedic applications (fracture repair, bone repair). And local drug delivery applications (antibiotics, anti-inflammatory and anti-cancer drugs).

In a preferred embodiment, the particles of the third component are made of a different substance than beta-tricalcium phosphate β-Ca ₃ (PO ₄ ) ₂ (β-TCP). The particles of the third component are preferably of the following group: hydroxylapatite; biphasic calcium phosphate (BCP) (HA / β-T
CP) mixtures; bioglass; or polymeric materials.

It is advantageous to have such differential degradation of the cement. The cement matrix degrades faster than the remaining particles. This is particularly useful for osteoporotic applications or for the remodeling of jaw ridges, in which case slowly degrading particles, for example made of hydroxyapatite or BCP, are desired.

The following reports five specific examples of producing a provisional bone substitute according to the present invention.

[0032]

【Example】

Example 1 The first component (containing powder particles) consists of two separate subcomponents A and B. Sub-component A comprises 0.8 g of monocalcium phosphate monohydrate Ca (H ₂ PO ₄ ) ₂
- consisting of H ₂ O MCPM particles. Subcomponent B is 1.2 g beta tricalcium phosphate β-Ca ₃ (PO ₄ ) ₂ (β-TCP) particles having a Ca / P atomic ratio in the range of 1.44 to 1.47, -TC
A mixture of P particles having a median particle diameter of 5 μm and a specific surface area of less than 2 m ² / g; and 0.012 g of sodium pyrophosphate Na ₂ H ₂ P ₂ O ₇ . The second component (containing the liquid) consists of 0.80 to 0.90 ml of a 0.10 M aqueous sulfuric acid solution. The third component, which can be mixed with the first component as subcomponent C, is 0.5-0.7
0.5 g (β) having a diameter in the range of 1 mm and a Ca / P atomic ratio in the range of 1.46
-TCP) particles. The powdered subcomponent is sterilized by gamma irradiation. Liquid components are prepared under sterile conditions using sterile materials. The hydraulic cement paste is prepared using a pestle. Carefully mix side component A with the liquid component in a mortar for about 1 minute. Thereafter, the auxiliary component B is added, and the mixture is carefully kneaded with a spatula for about 1 minute until a uniform paste is obtained. This paste can be used for about 10 minutes, depending on the ambient temperature; the higher the temperature, the shorter the cure time. The use of chilled materials and preparation equipment helps to extend the effective working time.

Example 2 The first component (containing the powdered particles) had an average diameter of 6 μm and a Ca /
It consists of 1.3 g of β-TCP particles with a P molar ratio and 0.7 g of MCPM. A third component is added to the first component to obtain 0.3 g of β-TCP particles having an average diameter in the range of 0.35 to 0.50 mm and a Ca / P molar ratio of 1.42. Including. The second (liquid) component is a solution of 1.6 ml of water and 100 mg of gentamicin sulfate. The powder / liquid components were mixed together for 30 seconds and the resulting cement paste was filled into an injector for application to bone defects.

Example 3 The first component (containing powdered particles) has an average diameter of 6 μm and a Ca /
It consists of 1.3 g of β-TCP particles with a P molar ratio and 0.7 g of MCPM. The third component is added to the first component, and the third component includes 0.8 g of hydroxyapatite (HA) particles having an average diameter in the range of 0.35 to 0.50 mm. The second (liquid) component is a solution of 1.6 ml of a 0.16 M aqueous sulfuric acid solution and 100 mg of gentamicin sulfate. The powder / liquid components were mixed together for 30 seconds and the resulting cement paste was filled into an injector for application to bone defects.

Example 4 1.5 g β-TCP with an average diameter of 2 μm and a Ca / P molar ratio of 1.46
Particles, average diameter comprised in the range of 0.35 to 0.50 mm and Ca / P of 1.42
0.3 g of β-TCP particles having a molar ratio, and 3M H ₃ PO ₄ and 0.1M
Of H ₂ SO ₄ and 1.5 ml of a 0.1 M solution of Na ₂ H ₂ P ₂ O ₇ were mixed together for 30 seconds, placed in a syringe and injected into the bone cavity.

Example 5 1.5 g β-TCP having an average diameter of 2 μm and a Ca / P molar ratio of 1.46
Particles, hydroxyapatite (HA) particles of 0.3g having an average diameter within the scope of 0.35～0.50Mm, and 3M of H ₃ PO ₄ and 0.1M of H ₂ S
O ₄ and a solution of 1.5ml of Na ₂ H ₂ P ₂ O ₇ in 0.1 M, were mixed together for 30 seconds, placed in a syringe and injected into the bone cavity.

[Procedural Amendment] Submission of translation of Article 34 Amendment of the Patent Cooperation Treaty

[Submission date] April 4, 2000 (200.4.4)

[Procedure amendment 1]

[Document name to be amended] Statement

[Correction target item name] Claims

[Correction method] Change

[Correction contents]

[Claims]

[Procedure amendment 2]

[Document name to be amended] Statement

[Correction target item name] 0021

[Correction method] Change

[Correction contents]

In a further preferred embodiment of the present invention, the particles having an average diameter larger than the average diameter of the beta-calcium phosphate β-Ca ₃ (PO ₄ ) ₂ (β-TCP) particles of the first component. Is added. This leads to an agglomerate structure of the final hardened cement, whereby the third component particles are embedded in the brushite matrix formed in the hardening process. The average particle diameter of the third component is at least twice, preferably at least 10 times larger than the average diameter of the first component beta-tricalcium phosphate β-Ca ₃ (PO ₄ ) ₂ (β-TCP) particles. Should be. Preferably the average particle diameter of the third component should be in the range of 50-2000 μm. The particles of the third component can consist of hydroxyapatite particles or polymer particles such as lactide, polysaccharide, collagen or protein.

[Procedure amendment 3]

[Document name to be amended] Statement

[Correction target item name] 0022

[Correction method] Change

[Correction contents]

In a further preferred embodiment of the invention, two different types of β-TCP particles are used, wherein the first type has less than 10% by volume of the particles being less than 1 μm, 5 μm
The second type is particles having an average diameter in the range of 150-500 μm, preferably in the range of 250-400 μm. The average particle diameter of the third component should be in the range of 50-2000 μm, preferably 2
It should be between 50 μm and 750 μm.

──────────────────────────────────────────────────続 き Continuation of the front page (71) Applicant Bischmattstrasse 12, Postfach, CH-2544 Bettlach, Switzerland (71) Applicant Eimattstrasse 3, CH-4436 Oberdorf, Switzrland, CHB, Netherlands, 71st Applicant −2544 Bettlach, Switzerland (71) Applicant Eimattstrasse 3, CH −4436 Oberdorf, Switzerland Rande (72) Inventor Remaitre Jacques, Switzerland Tseher-1012 Switzerland, Lausanne, Shemin de la Faubette 30 Inventor 72 Efbaumann, invention of 30 Ebbot Sui 8051 Zurich, Zurich, Luegislandstraße 372 (72) Inventor Van Randuit Pascal, Switzerland Zeeha-1024 Ecublens, Shemin des Parlettes 1, Les Bres d'Or (No address) F-term (reference) 4C081 AB03 AB04 AB06 AC03 AC04 BA16 BC02 CA082 CA182 CD012 CD022 CD032 CD042 CD082 CD092 CD112 CD132 CE01 CE02 CE08 CE11 CF011 CF021 CF032 CF112 DA11 DC12 DC13 EA05 4C089 AA06 BA02 BA03 BA16 BA18 BC05 BC20 BE14 BE15 CA02 CA07

Claims (36)

[Claims] (1) beta tricalcium phosphate β-Ca ₃ (PO ₄ ) ₂ (β-
TCP) particles; and monocalcium phosphate Ca (H ₂ PO ₄ ) ₂ (MCPA)
Particles or monocalcium phosphate monohydrate Ca (H ₂ PO ₄ ) ₂ .H ₂ O (MC
PM) a first component containing particles or phosphoric acid; a second component containing water; and the beta-tricalcium phosphate β-Ca ₃ (PO ₄ ) _{2 of} the first component (
(β-TCP) a third component comprising particles having an average diameter greater than the average diameter of the particles;
Thereby mixing the three components together to produce a brushite CaHPO ₄
· 2H ₂ hardened mass containing O (DCPD) is formed, a surgical cement, a) the beta-TCP particles have an average specific surface area of less than 10m ² / g; b) the third The component is calcium phosphate having a Ca / P ratio different from 1.5; and c) the third component comprises 1-99 volume percent of the cured mass.
The surgical cement according to any one of the preceding claims. 2. The method according to claim 1, wherein the first component is beta-tricalcium phosphate β-Ca_Three (
PO_Four )_Two (Β-TCP) particles and monocalcium phosphate Ca (H_Two PO_Four 
)_Two (MCPA) particles or monocalcium phosphate monohydrate Ca (H_Two PO_Four ) _Two ・ H_Two The cement of claim 1, comprising O (MCPM) particles.
. 3. The setting time of said cement measured at 25 ° C. is at least 2
3. Cement according to claim 1 or 2, characterized in that it has a duration of at least 3 minutes. 4. The setting time of said cement measured at 25 ° C. is at least 5
4. The cement according to claim 3, wherein the cement is a minute. 5. The cement according to claim 1, wherein the β-TCP particles have an average specific surface area of 0.0137 to ² m ² / g. 6. The cement according to claim 5, wherein the β-TCP particles have an average specific surface area of 0.8 to 1.5 m ² / g. 7. The cement according to claim 1, wherein the first component further comprises a setting speed modifier. 8. The first component is divided into three sub-components X, Y and Z, wherein the sub-component X comprises MCPA particles and / or MCPM particles and the sub-component Y comprises β
8. A cement according to claim 7, comprising-TCP particles and a setting speed modifier, and wherein the secondary component Z comprises a third component. 9. The method according to claim 1, wherein the curing rate controlling agent is sodium pyrophosphate, potassium pyrophosphate, sodium acetate, potassium acetate, sodium citrate, potassium citrate, sodium lindate, potassium linteate, sodium sulfate or potassium sulfate. Calcium sulfate hemihydrate CaSO ₄ .0.5H ₂ O (CSH),
Sodium pyrophosphate Na ₄ P ₂ O ₇ .10H ₂ O (NaPPH), sodium dihydrogen pyrophosphate Na ₂ H ₂ P ₂ O ₇ (NaHPP), calcium pyrophosphate C
_{a 4 P 2 O 7 (CaPP} ), cement according to claim 7 or 8, wherein the selected from the group consisting of sodium or potassium hydrogen phosphonate magnesium sulphate and heavy phosphonic acid. 10. The cement according to claim 1, wherein the second component further comprises orthophosphoric acid (OPA) and / or sulfuric acid (SA). 11. The total weight W _{TCP of} the first and third component β-TCP particles is expressed by the following formula: W _T = W _MCPA /0.7546+W _MCPM /0.8127+W _OPA /
0.3159 + W _SA /0.3162 (where W _MCPA , W _MCPM , W _OPA and W _SA are the MCPA, MCPM, O
11. The cement according to claim 1, wherein the weight is greater than the weight of each of PA and SA. 12. The method of claim 11, wherein the weight W _TCP is cement according to claim 11, characterized in that the range of _{1.2W T ≦ W TCP ≦ 10.0W T} . Wherein said weight W _TCP is cement according to claim 12, characterized in that the range of _{2W T ≦ W TCP ≦ 5W T} . 14. The average particle diameter of the third component is at least twice as large as the average diameter of beta-tricalcium phosphate β-Ca ₃ (PO ₄ ) ₂ (β-TCP) particles of the first component, preferably. 14. A cement according to any one of the preceding claims, wherein the cement is at least 10 times larger. 15. The method according to claim 1, wherein the average particle diameter of the third component is in the range of 50 to 2000 μm, preferably between 250 and 750 μm.
15. The cement according to any one of the items 14 to 14. 16. The cement according to claim 1, wherein the third component contains hydroxyapatite particles. 17. The cement according to claim 1, wherein the third component comprises polymer particles. 18. Two different types of β-TCP particles are used, the first being particles having a median particle size of 5 μm, wherein less than 10% by volume of the particles are less than 1 μm; and 18. A cement according to any one of the preceding claims, wherein the mold is a particle having an average diameter in the range 150-500 [mu] m, preferably 250-400 [mu] m. 19. The Ca / P atomic ratio of the β-TCP particles of the first component is 1.
19. Cement according to any of the preceding claims, characterized in that it is comprised between 350 and 1.499, preferably between 1.45 and 1.47. 20. The cement according to claim 19, wherein said Ca / P atomic ratio is comprised between 1.455 and 1.465. 21. Cement according to claim 1, wherein one of the two components further comprises a biodegradable polymer. 22. The biodegradable polymer is a polysaccharide derivative, preferably hyaluronic acid, dextran, hydroxypropylmethylcellulose; a chitin derivative, preferably chitosan; xanthan gum; agarose; polyethylene glycol (PEG), polyhydroxyethylene methacrylate (HEMA). 22. The cement according to claim 21, wherein the cement is selected from the group consisting of a synthetic protein and a natural protein; or collagen. 23. When the volume _VL of the second component is _equal to the volume V _T = (W _MCPA × 0.6
_{15 + W MCPM × 0.5 + W} OPA × 1.102 + W SA × 1.101) ml / g or equal cement according to any one of claims 1 to 22, characterized in that a larger and. 24. relationship between the volume V _T of the volume V _L of the second component the first component is in the range of _{0.5V T ≦ V L ≦ 10.0V T} , preferably 1.2V _T ≦ V _L ≤
Cement according to any one of claims 1 to 23, characterized in that in the range of 2.0 V _T. 25. The first component further comprising a pharmaceutically or physiologically active substance, preferably selected from the group consisting of antibiotics, anti-inflammatory drugs, anti-cancer drugs and bone growth factor. The cement according to any one of claims 1 to 24, characterized in that: 26. The method according to claim 25, wherein the antibiotic is selected from the group consisting of aminoglycosides, vancomycins, gentamicins or salts thereof, preferably gentamicin sulfate or gentamicin clovefat. cement. 27. Cement according to claim 26, wherein the antibiotic is a mixture of aminoglycosides, preferably a mixture of gentamicin and vancomycin. 28. The method according to claim 1, wherein the first component comprises at least 50 weight percent beta tricalcium phosphate β-Ca ₃ (PO ₄ ) ₂ (β-TCP). Cement according to item. 29. The particle of the third component, wherein the beta-tricalcium phosphate β-
The cement according to any one of claims 1 to 28, wherein the cement is made of a substance other than Ca ₃ (PO ₄ ) ₂ (β-TCP). 30. The particle of the third component, wherein the particle is made of a substance selected from the group consisting of hydroxylapatite; a biphasic calcium phosphonate (HA / β-TCP) mixture; bioglass; 30. The cement according to claim 29, characterized by the fact that: 31. A cement as claimed in any one of claims 1 to 30, wherein the third component comprises 1 to 99 volume percent of the hardened mass. 32. The composition according to claim 17, wherein the third component is less than 1.5, preferably from 1.35-1.
32. Cement according to any of the preceding claims, which is a calcium phosphate having a Ca / P ratio in the range of 49. 33. Cement according to claim 1, wherein the third component is a calcium phosphate having a Ca / P ratio of more than 1.5, preferably hydroxyapatite. . 34. brushite CaHPO ₄ · 2 as temporary bone replacement material
A method of manufacturing a matrix of H ₂ O (DCPD), the method by mixing together the two components according to any one of claims 1 to 33, wherein the curing. 35. temporary bone replacement material, brushite CaHPO ₄ · 2H ₂
35. A temporary bone substitute obtained by the method of claim 34, comprising O (DCPD). 36. The method of claim 34, wherein the temporary bone substitute comprises beta-tricalcium phosphate β-Ca ₃ (PO ₄ ) ₂ (β-TCP) particles embedded in the brushite matrix. A temporary bone substitute as described.