CN1295485A - Biologically degradable cement exhibiting improved properties - Google Patents
Biologically degradable cement exhibiting improved properties Download PDFInfo
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Abstract
The invention relates to biologically degradable calcium phosphate cement, especially mixtures of powders which contain calcium phosphate and which are of a different stoichiometric composition, exhibiting improved properties. The inventive mixtures all contain tricalcium phosphate (TCP) and one or more other compounds which contain phosphate and which are of a different composition, whereby the TCP portion is available in a well-defined range of particle sizes.
Description
The present invention relates to biodegradable calcium phosphate cements with improved properties, in particular to powder mixtures containing calcium phosphate of different stoichiometric compositions. The mixtures according to the invention all contain tricalcium phosphate (TCP) and one or more other phosphate-containing inorganic compounds of different composition, the contents of TCP being present in a well-defined range of particle sizes.
Naturally occurring bone materials are all composed of calcium phosphate with a hydroxyapatite structure. However, the composition of bone mineral and crystalline hydroxyapatite (Ca)10(PO4)6(OH)2) The ideal stoichiometric composition of (b) does not correspond but usually has a non-stoichiometric composition due to the introduction of other anions than orthophosphate, for example carbonate or hydrogen phosphate, but also other cations, for example sodium, potassium or magnesium, than calcium.
Biodegradable calcium phosphate cements (CaP) are increasingly attracting attention in traumatology and orthopedics due to the limited availability of autologous bone and the problems of biocompatibility of the autogenous bone. The disadvantage of many of the synthetic bone substitutes available on the basis of calcium and phosphorus is mainly that these substitutes are not degradable.
In recent years, it has become possible to prepare synthetic bone materials based on hydroxyapatite-like calcium phosphate compounds, which are very similar to natural bone due to the similarity in texture and structure. The known disadvantages caused by the harvesting of natural autogenous or allogenic bone can thus be avoided. Furthermore, these materials have the advantage of being able to withstand mechanical loads in fact like natural bone, which means that they are used in more major bone defects or fractures.
The main components of these materials are, for example, tricalcium phosphate (TCP), dicalcium phosphate (DCP) and tetracalcium phosphate (TTCP), which react with water in the presence of water to form hydroxyapatite, which is the final product of the cement-forming reaction. As the hydroxyapatite formed in this way is formed in an aqueous environment, it is more similar to biological apatite than hydroxyapatite produced at high temperatures. Such cements are therefore osteo-conductive and suitable for bone repair and reconstruction. Such cements can be rapidly integrated into bone structures and then transformed into new bone tissue using the cellular activity of osteoblasts.
Depending on the conditions, substantially the following solids may occur in Ca (OH)2-H3PO4-H2In the system of O:Ca(H2PO4)2·H2O (MCPM)CaHPO4 (DCP)CaHPO4·2H2O (DCPD)Ca8(HPO4)2(PO4)4·5H2O (OCP)Ca9(HPO4)(PO4)5OH (CDA)Ca10(PO4)6(OH)2 (PHA)Ca3(PO4)2·H2O (ACP)Ca3(PO4)2 (α,β-TCP)
such cements are disclosed, for example, in US4, 518, 430, US4, 612, 053, US4, 678, 355, US4, 880, 610, US5, 053, 212, US5, 152, 836, US5, 605, 713, EP0, 416, 761, EP0, 543, 765, EP0, 664, 133 or WO 96/36562.
Furthermore, the prior art has disclosed a cement consisting of α -TCP, β -TCP and a small amount of Precipitated Hydroxyapatite (PHA) as a nucleus of crystallization, and the solidification behavior of the cement has been studied (Jansen et al, J. materials science: Material medicine 6(1995) 653-: the following equation is a general equation for the reaction of α -TCP with dicalcium phosphate (DCP): 。
during the setting process, the inter-engagement of the precipitated calcium-deficient hydroxyapatite crystals hardens the initially pasty mixture.
The properties of the known calcium phosphate cements, in particular their physiological acceptability with a view to obtaining a bioabsorption capacity and an ability to be replaced by new natural bone tissue or a stimulating effect on the growth of natural bone tissue, certain of their physical properties, such as compressive strength and hardening time, will depend on a more or less pronounced crystallinity, on the particle size and on the porosity which may be obtained during preparation.
Thus, for example, CaHPO4Or CaCO3Or CaHPO4Together with CaCO3Different biocements were obtained by adding a single charge of α -TCP and β -TCP to the mixture (Khairoun et al, biomaterials, 10(1997) 1535) -1539) the compressive strength of some of the compositions obtained after hardening was in the range of 30MPa and therefore in the range of human trabecular bone (Driessens et al, bioceramics 10(1997)279-282), although this was done so thatIn these cases α -TCP blends have been ground to a powder of about 60% -70% having a particle size of less than 8 microns and the remainder having a particle size of less than 35 microns.
Therefore, there is still interest in bone cements with different properties in order to meet different requirements. The present invention provides a cement having specific characteristics. The problem on which the present invention is based is more precisely that of varying the size of the grinding of the blend of TCP mixture together with other inorganic phosphate compounds, whether or not new cements with improved characteristics can be obtained.
The invention therefore relates to a mixture of powders suitable for the preparation of absorbable calcium phosphate cements, which, in addition to tricalcium phosphate (TCP), at least further comprise other inorganic phosphate-containing compounds, characterized in that the particles of TCP have the following particle size distribution:
30-90%: 0.1-40 microns of the total particle size,
10-70%: 40-300 microns.
It is essential to the invention that, in addition to a certain proportion of coarse particles, a certain proportion of fine particles (about 1 to 40 microns) and very fine particles (about 0.1 to 1 micron) must be present.
TCP must always be present in the mixture according to the invention in two different crystalline forms, namely α and β. according to the invention, it is possible for the mixture to contain α -TCP, up to 60% of β -TCP being incorporated, the invention therefore relates to a mixture in which 40-100% of TCP is present in the α -form (α -TCP) and 0-60% is present in the β -form (β -TCP). when the terms TCP are used above or below, this mixture of α -and β -TCP is always referred to by definition.
The invention relates in particular to those mixtures, 30 to 70% of the particles of TCP being 0.1 to 7 microns. Furthermore, the invention relates to those mixtures wherein 10-60% of the TCP particles are 40-100 microns. The corresponding mixtures having the following particle size distributions of TCP are particularly preferred:
30-50%: 1-7 microns
20-40%: 7-40 microns
10-50%: 40-100 microns
It has been found that not only the particle size of the TCP particles or their particle size distribution has a favourable effect, but also the particle size and the properties of the remaining phosphate-containing compound in the mixture. According to the invention, at least 50% of these non-TCP particles should have a particle size between 10-100 microns. Generally, these particles can be neither ground too finely nor too coarsely. According to the invention, the proportion of these non-TCP compounds in the mixture is 1-85%, preferably 5-60%.
Suitable compounds which can be mixed with TCP are generally inorganic compounds containing calcium and phosphate. EP 543765 discloses particularly suitable compounds. Compounds selected from the following are preferred. Ca (H)2PO4)2·H2O、CaHPO4、CaHPO4·2H2O、Ca8(HPO4)2(PO4)4·5H2O、Ca9(HPO4)(PO4)5OH、Ca10(PO4)6(OH)2Carbonate-containing apatite, CaCO3、Ca(OH)2、MgHPO4·3H2O、Mg3(PO4)2、CaNaPO4、Ca11Na(PO4)2、CaKPO4、Ca2PO4Cl、Ca2NaK(PO4)2、Ca10(PO4)6Cl2、ZnHPO4·4H2O and Zn3(PO4)2In particular selected from the group: ca8(HPO4)2(PO4)4·5H2O、Ca10(PO4)6(OH)2、CaHPO4And CaCO3·
In summary, mixtures having the following composition are particularly suitable: TCP: 90-99% Ca10(PO4)6(OH)2：1-10％；(ⅱ)TCP：90-99％ Ca8(HPO4)2(PO4)4·5H2O：1-10％；(ⅲ)TCP：70-99％ Ca10(PO4)6(OH)2：1-10％， CaCO3：10-20％；(ⅳ)TCP：70-99％ Ca8(HPO4)2(pO4)4·5H2O：1-10％， CaCO3：10-20％；(ⅴ)TCP：40-99％ Ca10(PO4)6(OH)2：1-10％， CaHPO4：1-50％；(ⅵ)TCP：40-99％ Ca8(HPO4)2(PO4)4·5H2O：1-10％， CaHPO4：1-50％；(ⅵ)TCP：20-99％ Ca10(PO4)6(OH)2：1-10％， CaHPO4：1-50％， CaCO3：1-20％；(ⅶ)TCP：20-99％ Ca8(HPO4)2(PO4)4·5H2O：1-10％， CaHPO4：1-50％， CaCO3：1-20％。
The mixtures according to the invention may also contain known hardening accelerators, if desired. Disodium hydrogen phosphate is preferred here.
Furthermore, it has been found that the TCP containing biocement of the present invention is particularly advantageous if the magnesium content in the raw material is not more than about 0.13% and the sodium content is not more than about 0.2%.
Transplantation of biological materials in the human or animal body these inanimate materials are always presentAre at risk to microbial populations because these materials are initially free of vascular associations and, therefore, are not protected by the immune system. It is therefore desirable to add antibiotics, for example from the class of aminoglycosides, such as gentamicin, or cefazolin, clindamycin palmitate, especially clindamycin phosphate, or disinfectants to the biological material to temporarily isolate the biological material from the population of microorganisms to avoid the population of microorganisms during the translocation. This leads to the next objective of demonstrating that antibiotics and/or disinfectants are not only incorporated into the cement, but also eluted from the cement. Furthermore, the mixing of antibiotics and/or disinfectants, depending on the intended use, does not adversely affect the mechanical or processing characteristics of the cement, such as the setting time. Suitable disinfectants are acridines, in particular biguanides, such as chlorhexidine, and in particular polyhexamethylene biguanide (Lavaset)_). Furthermore, this biomaterial can migrate after surgical debridement in areas at risk of infection by means of the incorporation and gradual escape of antibiotics and disinfectants from absorbable calcium phosphate cements. In addition, since osteomyelitis can be treated by one operation, it is easy to treat osteomyelitis, which is characterized by chronic infection and osteonecrosis.
Furthermore, it is desirable to combine additional pharmaceutically active ingredients with absorbable biological cements that have a broad spectrum of efficacy, for example, to increase cellular activity of bone surrounding the cement, in the chemotherapeutic sense to increase cement absorption and replacement of the cement by endogenous bone or to form portions of endogenous and non-absorbed cement, or a composite of active ingredients, which chemotherapy prevents the stable cement filling from being loosened by the tumor cells left nearby after tumor resection.
Examples of such suitable pharmaceutical active ingredients are various growth factors, such as FGF (fibroblast growth factor), BMP (osteogenic protein) or TGF- β (tissue growth factor), or other active ingredients, such as prostaglandins or other substances affecting the metabolism of prostaglandins, active ingredients capable of interacting with the metabolism of the thyroid gland or bone marrow glands, or also chemotherapeutic agents, such as methotrexate.
The invention therefore also relates to mixtures which also contain one or more pharmaceutically active ingredients or one or more disinfectants.
For implantation or injection, the mixture according to the invention must be mixed with an aqueous liquid so that the setting or formation of the apatite structure or apatite-like substance takes place according to the reaction equation described previously. As a result, advantageous properties are obtained when the powder mixture is mixed with an aqueous liquid. These characteristics are characterised in that the paste obtained after mixing of the solid and liquid phases, in a temperature-dependent manner over a certain time interval, allows certain processing possibilities, such as modelling and injectability. Suitable aqueous liquids are, for example, physiological saline solutions, body fluids such as blood or plasma, or aqueous buffer solutions. In principle, additives such as pharmaceutically active ingredients or hardening accelerators can be mixed not only with the TCP powder but also in the form of aqueous solutions to the biological cement to be stirred. It is then in the form of a creamy suspension or paste which can be easily introduced into the intended site or defective bone structure.
The invention therefore also relates to corresponding mixtures in the form of aqueous solutions, pastes or suspensions and to the use of the mixtures for producing biodegradable synthetic bone materials.
The stirred and solidified mixture according to the invention is characterized by a desired compressive strength of 30MPa or more, which, depending on the composition of the mixture, can be reached with only a very short hardening time, i.e. in the range of 2-10 hours, preferably in the range of 3-6 hours, whereas in the prior art, in the case of a mixture of slightly modified composition, the hardening time is usually in the range of 15-30 hours, the compressive strength of which is only slightly higher than 30 MPa. In the case of the mixtures according to the invention, the compressive strength can be as high as 40 to 50MPa in such long hardening times.
The drawings will be briefly described below.
FIG. 1: elution of antibiotics from biological Cement D
Batch materials:
1 g of cement +0.7 ml of Refobacin 120; 0.7 g of the above mixture per 20 ml of buffer (=20 mg)
II.1 ml of pharmaceutical 5-agar +0.7 ml of rivastigmine 120/20 ml of buffer.
III.1 g of cement +0.7 ml of 60 mg/ml cefazolin; 1.04 g of the above mixture per 20 ml of buffer (=25.7 mg)
IV.1 g cement +0.7 ml of 60 mg/ml netilmicin, 1.15 g/20 ml buffer (=28.4 mg)
V.1 g cement +0.7 ml clindamycin phosphate 60 mg/ml, 0.99 g/20 ml buffer (=25.4 mg)
Eluting with 1/15M phosphate buffer solution at pH7.4 at 37 deg.C
Paragraphs I-V correspond to identically numbered curves in the figures.
FIG. 2: release of gentamicin from H-, B-, F-and D-cements (expressed in μ g)
| Mixture of | 1 | 2 | 3 | 4 | |
| Cement
Buffer solution
Gentamicin%
| H | 20 4.2 Na2HPO4 | B 20 4.2 Na2HPO4 | F 20 4.2 Na2HPO4 | D 20 4.2 Na2HPO4 |
| 1 | 249.13 18.93 7.05 6.63 3.91 4.05 2.53 1.83 1.39 1.86 | 308.28 21.35 8.96 7.20 4.14 4.07 3.57 2.96 3.75 3.20 | 238.91 29.55 12.30 9.05 6.44 5.15 5.13 2.55 2.96 2.75 | 302.06 22.16 14.02 12.64 9.44 7.95 6.71 3.74 4.55 3.99 | |
| Sum of | 290.37 | 367.47 | 314.78 | 387.27 |
The numbering of the mixtures corresponds to the curves of the same numbering.
Example 1:
α -TCP was CaHPO used in a 2: 1 molar ratio4With CaCO3Is prepared by calcining the mixture of (1), the calcining is carried out at 1350 ℃ for 4 hours, and then the calcining is carried out in a roomThe resulting reaction product contained less than 10% β -TCP.
α -TCP was ground, sieved, and mixed so that about 50% of the particles were between 0.1 and 7 microns, about 25% were between 7 and 25 microns, and the other 25% were between 25 and 80 microns.
The following cement mixtures are characterized by the examples:
the following are included:
biological cement H α -mixture of TCP and PHA
Biocement F α -mixture of TCP, DCP and PHA
The biological cement D is α -TCP, DCP, CaCO3And mixtures of PHAs
Mixture of biological cement H-OCP α -TCP and OCP
Mixture of biological cement F-OCP α -TCP, DCP and OCP
The biological cement D-OCP is α -TCP, DCP, CaCO3Mixture of OCP and biological cement α -TCP DCP CaCO3 PHA OCP
α-TCP 20 - - - -
H 20 - - 0．40 -
H-OCP 20 - - - 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
The mixing ratio data is in grams. The liquid used to mix the powders was 4%Na of (2)2HPO4An aqueous solution of (a). The liquid/powder ratio was 0.30 ml/g powder.
The initial hardening times (t) at room temperature (20. + -. 1 ℃ C.) and (37. + -. 1 ℃ C.) were determined according to ASTM standards with a Gilmore needlei) And time to final hardness (t)f)。
The compressive strength was measured using a lloyd model LR50K materials tester at 1 hour, 2 hours, 4 hours, 18 hours and 65 hours after immersion in Ringer solution. The reaction products were determined by means of X-ray diffraction.
Particularly preferred DCPs for the preparation of biocement F, F-OCP, and D-OCP are DCPs having a Ca/P ratio of greater than 1.45, which biocement has the common feature of being incorporated with DCP.
Example 2:
the antibiotic/disinfectant is mixed into the resulting cement in liquid and solid form and the release behaviour is measured. The elution solution used was phosphate buffer according to S _ rensen at pH7.4 and temperature 37 ℃.
The hardening properties of the antibiotic/disinfectant containing cement mixes were determined according to ASTM standards.
X-ray diffraction method shows that CaHPO in F-OCP and D-OCP4No reaction takes place, although the additional OCP acts as a nucleus and calcium deficient hydroxyapatite is formed.
Setting times (minutes) at 20 ℃ and 37 ℃ as ti and tf (standard deviation):biological cement ti(20℃) ti(37℃) tf(20℃) tf(37℃)
α-TCP 31(1) 4．5(0．25) 51(1) 7(0．5)
H 19(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(0．5)
F-OCP 10(0．5) 3．5(0．25) 16．5(1) 4．5(0．25)
D 9．75(0．5) 3．5(0．25) 19(1) 8．25(0．5)
Compressive strength of D-OCP 11.5 (0.5) 3 (0.25) 22(1) 6.5 (0.5) after 1, 2, 4, 18 and 65 hours: biological cement 1h 2h 4h 18h 65h
α-TCP 10(1) 18(1) 31(2) - 32(3)
H 11(1) 20(1) 38(2) 40(4) 41(5)
H-OCP 13(1) 18(2) 37(3) 40(5) -
F 11(1) 18(3) 28(3) 31(4) 39(2)
F-OCP 11(1) 29(1) 32(2) 42(3) 41(2)
D 10(2) 16(1) 26(2) 45(5) 47(2)
D-OCP 10(1) 16(2) 23(1) 45(3) 47(6)
The results show that the object of the invention has been achieved in comparison with α -TCP with addition of OCP and PHA (with a content of 10% β -TCP). the initial and final hardening times are shortened, the hardening kinetics shift towards shorter times is particularly evident at low temperatures T, while at body temperatures the effect is only slight, which is particularly advantageous for the handling characteristics of the resulting cement, since a sufficiently long handling time is ensured at room temperature, while the hardening at body temperature is not too short, so that the introduced cement remains plastic.
Example 3:
it is shown below that a further object of the invention is also achieved, namely that active ingredients, such as antibiotics, are incorporated and gradually released from the cement for immigration protection or resistance against infection.
Figures 1 and 2 show the release kinetics of the biocement D selected by way of example and containing various antibiotics, and also the release kinetics of various biocements containing gentamicin. The hardening kinetics or strength is not adversely affected by the desired effect of the incorporation of the antibiotic/disinfectant on the release of the antibiotic. As the examples show, the results of using the biocement H, F and D with gentamicin phosphate powder, the liquid/powder ratio was 0.30, using Na2HPO4Or gentamicin phosphate solution at 37 deg.c. The intensity values were measured after 20 hours. t is tiAnd tfValues were measured in units of minutes using a Gilmoore needle. The time to Cohesion (CT) was measured at room temperature and expressed in minutes.
Measured values determined using gentamicin phosphate powder
120 mg/5 g cement biological cement ti tf CT F(MPa) ti tf CT F(MPa)
The non-gentamicin H3.56640 + -48141.537 + -3F 3.553.531 + -47.59.51.539 + -3D 45.51.545 + -5581.541 + -1
Gentamicin phosphate as a solution (Refobacin 120) containing no Na2HPO4 and only Na2HPO4Measured value of time biological cement ti tf CT F(MPa) ti tf CT F(MPa)
Refobacin 120_ Na2HPO4H 7 12 ＜2 48±4 3.5 6 6 40±4F 3.5 5 3.5 31±4 7.5 9.5 1.5 39±3D 4 5.5 1.5 45±5 5 8 1.5 41±1
Example 4:
preparation of TCP from raw materials
The percentage of α/β TCP in the preparation of TCP is primarily affected by the weight percentage of Mg and Na in the starting materials, but also by the Ca/P ratio, the following table gives an overview of the effect of Mg and Na on the composition of the TCP phase, the% Mg% Na being β -TCP0.110.1250.390.10700.250.022350.230.02525 < 0.00050.0024 < 5 < 0.00050.0029 < 5 < 0.00050.0013 < 50.0620.0081 < 50.110.721000.00240.20 < 50.130.20 < 5
Claims (17)
1. A powder mixture for the preparation of an absorbable calcium phosphate cement, the mixture comprising tricalcium phosphate (TCP) and at least one other inorganic phosphate-containing compound, the mixture being characterized in that the particles of TCP have the following particle size distribution:
30-90%: 0.1-40 microns
10-70%: 40-300 microns.
2. Mixture according to claim 1, characterized in that 30-70% of the TCP particles have a particle size comprised between 0.1 and 7 microns.
3. Mixture according to claim 1, characterized in that at least 10-60% of the TCP particles have a particle size comprised between 40 and 100 microns.
4. Mixture according to claim 1, characterized in that the TCP particles have the following particle size distribution:
30-50%: 1-7 microns
20-40%: 7-40 microns
10-50%: 40-100 microns.
5. Mixture according to any one of claims 1 to 4, characterized in that at least 50% of the remaining particles have a particle size between 10 and 100 μm.
6. Mixture according to any one of claims 1 to 5, characterized in that 40 to 100% of the TCP is present in the α -form (α -TCP) and 0 to 60% is present in the β -form (β -TCP).
7. Mixture according to any one of claims 1 to 6, characterized in that the other phosphate-containing compounds represent 1 to 85% of the total mixture.
8. Mixture according to any one of claims 1 to 7, characterized in that the at least one other phosphate-containing compound is chosen from: ca (H)2PO4)2·H2O、CaHPO4、CaHPO4·2H2O、Ca8(HPO4)2(PO4)4·5H2O、Ca9(HPO4)(PO4)5OH、Ca10(PO4)6(OH)2Carbonate-containing apatite, CaCO3，Ca(OH)2，MgHPO4·3H2O，Mg3(PO4)2，CaNaPO4，Ca11Na(PO4)2，CaKPO4，Ca2PO4Cl，Ca2NaK(PO4)2，Ca10(PO4)6Cl2，ZnHPO4·4H2O and Zn3(PO4)2。
9. The mixture according to claim 8, characterized in that at least one other phosphate-containing compound is selected from the group consisting of:Ca8(HPO4)2(PO4)4·5H2O、Ca10(PO4)6(OH)2、CaHPO4and CaCO3·
10. The mixture according to claim 9, whose overall composition is selected from: TCP: 90-99% Ca10(PO4)6(OH)2：1-10％；(ⅱ)TCP：90-99％ Ca8(HPO4)2(PO4)4·5H2O：1-10％；(ⅲ)TCP：70-99％ Ca10(PO4)6(OH)2：1-10％， CaCO3：10-20％；(ⅳ)TCP：70-99％ Ca8(HPO4)2(pO4)4·5H2O：1-10％， CaCO3：10-20％；(ⅴ)TCP：40-99％ Ca10(PO4)6(OH)2：1-10％， CaHPO4：1-50％；(ⅵ)TCP：40-99％ Ca8(HPO4)2(PO4)4·5H2O：1-10％， CaHPO4：1-50％；(ⅵ)TCP：20-99％ Ca10(PO4)6(OH)2：1-10％， CaHPO4：1-50％， CaCO3：1-20％；(ⅶ)TCP：20-99％ Ca8(HPO4)2(PO4)4·5H2O：1-10％， CaHPO4：1-50％， CaCO3：1-20％。
11. A mixture according to any one of claims 1 to 10, characterised in that the percentages of magnesium and sodium in the original composition do not exceed 0.13(Mg) and 0.2(Na), respectively.
12. Mixture according to any one of claims 1 to 11, characterized in that the mixture also contains a set accelerator.
13. Mixture according to any one of claims 1 to 12, characterized in that it further contains a pharmaceutically active ingredient.
14. Mixture according to claim 13, characterized in that it contains an antibiotic or antibiotic agent.
15. Mixture according to any one of claims 1 to 14, characterized in that it is in the form of an aqueous solution, a suspension or a paste.
16. A biodegradable implant produced from the hardened mixture of claim 15.
17. Use of a mixture according to claim 15 for the preparation of biodegradable implantable synthetic bone material.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19813614.5 | 1998-03-27 | ||
| DE19813614A DE19813614A1 (en) | 1998-03-27 | 1998-03-27 | Bio-cements with improved properties |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1295485A true CN1295485A (en) | 2001-05-16 |
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ID=7862589
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN99804569.1A Pending CN1295485A (en) | 1998-03-27 | 1999-03-17 | Biologically degradable cement exhibiting improved properties |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP1066065A1 (en) |
| JP (1) | JP2002509766A (en) |
| CN (1) | CN1295485A (en) |
| AU (1) | AU2933699A (en) |
| CA (1) | CA2325740A1 (en) |
| DE (1) | DE19813614A1 (en) |
| HU (1) | HUP0101520A3 (en) |
| PL (1) | PL342733A1 (en) |
| WO (1) | WO1999049906A1 (en) |
| ZA (1) | ZA200006034B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104906631A (en) * | 2014-03-14 | 2015-09-16 | 株式会社理光 | Layer stack formation powder material, powder layer stack formation hardening liquid, layer stack formation material set, and layer stack object formation method |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1153621A1 (en) | 2000-05-12 | 2001-11-14 | MERCK PATENT GmbH | Biocements based on a mixture of TCP-PHA with improved compressive strength |
| EP1335887A4 (en) | 2000-10-16 | 2004-06-23 | Univ South Carolina | Biocompatible cement containing reactive calcium phosphate nanoparticles and methods for making and using such cement |
| JP2002291866A (en) * | 2001-04-03 | 2002-10-08 | Ngk Spark Plug Co Ltd | Calcium phosphate cement powder and calcium phosphate cement |
| DE10249625B4 (en) | 2002-10-21 | 2005-08-04 | BAM Bundesanstalt für Materialforschung und -prüfung | Powder mixture for resorbable calcium phosphate biocements and their use |
| DK1933892T3 (en) | 2005-09-09 | 2013-03-25 | Agnovos Healthcare Llc | Composite bone graft replacement cement and articles made therefrom |
| EP2077126A1 (en) * | 2008-01-07 | 2009-07-08 | Graftys | Analgesic apatitic calcium-phosphate cement |
| JP5478872B2 (en) * | 2008-11-05 | 2014-04-23 | 国立大学法人東北大学 | Artificial aggregate |
| CN107296977B (en) | 2012-01-31 | 2021-03-23 | 托莱多大学 | Injectable, biodegradable bone cements and methods of making and using same |
| CN106587681B (en) * | 2016-12-06 | 2019-04-12 | 南昌大学 | A kind of preparation method of green construction material-biology cement |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4668295A (en) * | 1985-04-25 | 1987-05-26 | University Of Dayton | Surgical cements |
| DE3613213A1 (en) * | 1986-04-18 | 1987-10-22 | Merck Patent Gmbh | TRICALCIUMPHOSPHATE FOR IMPLANTATION MATERIALS |
| US5569442A (en) * | 1994-11-04 | 1996-10-29 | Norian Corporation | Reactive tricalcium phosphate compositions and uses |
-
1998
- 1998-03-27 DE DE19813614A patent/DE19813614A1/en not_active Withdrawn
-
1999
- 1999-03-17 WO PCT/EP1999/001738 patent/WO1999049906A1/en not_active Application Discontinuation
- 1999-03-17 CA CA002325740A patent/CA2325740A1/en not_active Abandoned
- 1999-03-17 JP JP2000540868A patent/JP2002509766A/en active Pending
- 1999-03-17 CN CN99804569.1A patent/CN1295485A/en active Pending
- 1999-03-17 AU AU29336/99A patent/AU2933699A/en not_active Abandoned
- 1999-03-17 HU HU0101520A patent/HUP0101520A3/en unknown
- 1999-03-17 EP EP99910351A patent/EP1066065A1/en not_active Withdrawn
- 1999-03-17 PL PL99342733A patent/PL342733A1/en unknown
-
2000
- 2000-10-26 ZA ZA200006034A patent/ZA200006034B/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104906631A (en) * | 2014-03-14 | 2015-09-16 | 株式会社理光 | Layer stack formation powder material, powder layer stack formation hardening liquid, layer stack formation material set, and layer stack object formation method |
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0101520A3 (en) | 2001-12-28 |
| HUP0101520A2 (en) | 2001-11-28 |
| DE19813614A1 (en) | 1999-09-30 |
| JP2002509766A (en) | 2002-04-02 |
| EP1066065A1 (en) | 2001-01-10 |
| PL342733A1 (en) | 2001-07-02 |
| AU2933699A (en) | 1999-10-18 |
| ZA200006034B (en) | 2001-08-10 |
| WO1999049906A1 (en) | 1999-10-07 |
| CA2325740A1 (en) | 1999-10-07 |
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