TW201217296A - Bone cement formula and bioresorbable hardened bone cement composites prepared with the same - Google Patents

Abstract

The present invention provides a bone cement formula having a powder component and a setting liquid component, wherein the powder component includes a calcium sulfate source and a calcium phosphate source with a weight ratio of the calcium sulfate source less than 65%, based on the total weight of the calcium sulfate source and the calcium phosphate source, and the setting liquid component comprises ammonium ion (NH4+) in a concentration of about 0.5 M to 4 M, wherein the calcium phosphate source includes tetracalcium phosphate (TTCP) and dicalcium phosphate in a molar ratio of TTCP to dicalcium phosphate of about 0.5 to about 2.5, and the calcium sulfate source is calcium sulfate hemihydrate (CSH), calcium sulfate dehydrate (CSD), or anhydrous calcium sulfate.

Description

201217296 VI. Description of the Invention: [Technical Field of the Invention] Exemplary embodiments of the present invention relate to a bone restorative substance for a drug. More specifically, an exemplary embodiment of the present invention relates to a bone cement formula (bone cement formula) 〇 [Prior Art] Bone cement compositions are widely used to bond, fill and/or repair damaged natural bone. Bone cement is commonly used for orthopedics, dental procedures, and/or other medical applications. Despite many advantages, such as excellent biocompatibility, excellent osteoconductivity, and enhanced mechanical strength or physical strength, most calcium phosphates exhibit clinically low bioresorption rates. . On the other hand, sulfate-fed compounds also show higher dissolution rates, and for many applications, in order to allow new bone cells to grow rapidly in the bone cavity, the dissolution rate is usually too high. • Composites containing calcium sulfate usually have a specific ratio. The composite of calcium phosphate has lower mechanical strength and/or physical strength. Another problem associated with conventional bone cement pastes is the prolonged cure time, thus impeding applicability to a variety of applications. For example, the calcium phosphate (CPC) paste described in U.S. Patent No. 4,612,053 generally requires an extended curing time. SUMMARY OF THE INVENTION Embodiments of the present invention disclose a method for providing a squaric acid-sulphuric acid compound 4 201217296 composite material. The composite material exhibits enhanced strength, excellent biocompatibility, excellent bone conductivity, and appropriate And adjustable bioresorption rate. It is an object of an embodiment to provide a bone cement formulation, a bone cement paste, a hardened bone cement composite formed from the paste, formed by pressurizing the paste while leaking a solution from the paste Enhanced strength hardened bone cement composite, and porous hardened bone cement composite formed from the paste. Embodiments of the present invention provide for providing a bone cement formulation, a bone cement paste, a hardened bone cement composite, A method of hardening a bone cement composite having enhanced strength, and a porous hardened bone cement composite. One embodiment of the present invention provides a method of filling a hole or cavity in a bone using an exemplary embodiment of a bone cement paste that solidifies or hardens in a hole or cavity that requires treatment. Another embodiment of the present invention provides a method of implanting a hardened bone cement composite during processing. One embodiment of the present invention provides a bone cement formulation comprising a powder component and a solidified liquid component, wherein the ratio of liquid to powder is from 0.20 cc/g to 0.50 cc/g (cc is cubic centimeters, g It is preferably 0.25 cc/g to 0.35 cc/g. In one aspect, the powder component comprises a source of calcium sulfate and a source of calcium phosphate based on the total weight of the source of calcium sulfate and calcium phosphate, the weight ratio of the source of calcium sulfate being less than 65. / (^ In one aspect, the solidified liquid component contains an ammonium ion (ΝΗ/) at a concentration of about 0.5 to 4 Torr. In one aspect, the calcium phosphate source comprises tetracalcium phosphate to be 201217296 and Dicalcium phosphate, wherein the molar ratio of TTCP to dicalcium phosphate is from about 5 to about 2.5', preferably 1.0, and the calcium sulfate source is calcium sulfate hemihydrate (CSH), dehydrated calcium sulfate (CSD) or anhydrous calcium sulfate. And preferably csh. It should be > the idea that 'the rate of absorption required for different medical indications can be different. Therefore, the more desirable cement should be able to provide a range of bone resorption rates' without significantly changing its primary Formulation, performance and working time / curing time. For example, 'the absorption rate of the implanted hardened cement composite is adjustable due to the coexistence of the calcium sulfate source and the calcium phosphate source. Animal studies have shown that by adjusting the sulfate/phosphate The ratio of the absorption rate of the hardened sulfate-phosphate cement composite can be adjusted. In an embodiment, the powder group is based on the total weight of the sulfuric acid source and the linonic acid source powder. The source of calcium sulfate is greater than 5%, and preferably from 10% to 55%. In one aspect, the calcium phosphate source comprises tetragonal tetraphosphate (TTCP) and bisenoate di', preferably DCPA, wherein TTCP is dichotomous with linonic acid The molar ratio is about 0.5-2.5, preferably about and the calcium sulfate source is calcium sulfate hemihydrate (CSH), dehydrated calcium sulfate (CSD) or anhydrous calcium sulfate, and preferably CSH. As in Comparative Example 1 - As explained or demonstrated in 4, a detailed discussion of the combination of TTCP, DCPA and CSH is necessary in the experimental program section below. Since TTCP, DCPA and CSH can be combined or mixed within a certain weight ratio range, it is available. Various unique and irreplaceable results. On the other hand, various experiments with mixtures of two compounds (such as TTCp/CSH and DCPA/CSH) produced unsatisfactory results, although generally considered to be a more toxic group. However, the experiments shown in 201217296 below show that ammonium not only provides a cytotoxic acceptable cement formulation' but also provides a cement formulation with unprecedented performance. When the concentration of ammonium ions is too low, water The paste may be dispersed upon contact with a liquid such as water or a body fluid (i.e., 'also liquid), or its initial mechanical strength is too low to maintain the integrity of the cement paste, which may cause the cement paste to rupture prematurely. In contrast, when the ammonium ion concentration is too high, the cement paste becomes too toxic to be used as an implant. In one embodiment, the solidified liquid component contains ammonium ions (NH4+) at a concentration of From about 1⁄2 to 2.0 M, more preferably about 1.2 M. In one example, the solidified liquid component is a solution of νη4η2ρο4, (ΝΗ4)2ΗΡ04, (ΝΗ4)3Ρ〇4.3Η20 or a mixture thereof. Preferably, the solidified liquid component is an aqueous solution. Optionally, the solidified liquid component further contains citric acid or tartaric acid dissolved therein. Preferably, the solidified liquid component has a pH of from about 7.0 to about 9.0. In one embodiment, the powder component contains a pore-forming agent that dissolves in the solution when the hardened bone cement composite is impregnated in solution. Preferably, the pore forming agent is selected from the group consisting of LiCn, KC, NaCn, MgCl2, CaCl2, NaI03, K1, Na3P〇4, K3P04, Na2C03, amino acid-sodium salt, amino acid-salt salt, glucose, polysaccharide , fatty acid-sodium salt, fatty acid-potassium salt, potassium hydrogen tartrate (khc: 4H4〇6), potassium carbonate, potassium gluconate (KC6Hu〇7), sodium potassium tartrate (KNaC4H4 (V4H2〇), potassium sulfate (K2S〇4) In the group consisting of sodium sulfate, sodium lactate and mannitol, the amount of pore former used is proportional to the desired porosity of the hardened bone cement composite.

In one embodiment, the calcium phosphate source is a mixture of TTCP and DCPA. In one aspect, the bone cement formulation provides the cement paste with the desired working time and cure time&apos; so that the operator has sufficient time to fill the pores or cavities with the paste before the paste becomes hard. It should be noted that the filled paste will form the minimum strength required for processing in an acceptable short period of time. In one embodiment, the hardened bone cement composite has low toxicity and, therefore, is safe, for example, when administered to a patient. It is noted that hardened bone cement has a high initial strength characteristic of increased bioresorbable rate. Further features and benefits of the present invention will be apparent from the following detailed description, drawings and claims. [Embodiment] Embodiments of the present invention are described herein in the context of methods, formulations, systems, and/or procedures for preparing a hardened bone cement composite having a medically enhanced bioresorbable rate. It is to be understood by those skilled in the art that <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; Other embodiments of the invention will be readily apparent to those skilled in the art from this disclosure. Reference is made to "one embodiment", "one embodiment", "embodiment embodiment", various embodiments, "exemplary embodiment", "one aspect", "one aspect", "exemplary aspect", DETAILED DESCRIPTION OF THE INVENTION [0014] </ RTI> </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> <RTIgt; </ RTI> </ RTI> </ RTI> <RTIgt; The short σ used in the embodiments "does not necessarily refer to the same embodiment, but may also be the same embodiment β, for the sake of clarity, not all of the traditional features of the implementation and/or method are described and description. Of course, it should be understood that in developing any such actual implementation, numerous implementation-specific decisions are made to achieve the developer's specific goals, such as application- and business-related restrictions, and these specific goals can be different. Implementation and changes among different developers. Moreover, it should be understood that such development plans may be complex and time consuming, but are within the ordinary skill of ordinary skill in the art having the benefit of the present disclosure. A particular embodiment of the invention is a bioresorbable bone cement suitable for use in a variety of medical fields, such as orthopedic, spinal and root canal surgery. The properties or properties of the bioresorbable bone cement or formulation have a convenient working environment and curing time to form high strength, excellent biocompatibility and excellent osteoconductivity as well as adjustable (or flexible) a hardened block of bioresorption rate. In order to prepare or produce a bioresorbable bone cement, the bone cement has a flexible (or convenient) working environment (or time) and curing time performance to form a hardened bone having the desired strength and biocompatibility. Cement Composite, an embodiment of the present invention discloses a bone cement formulation, which will be described in more detail below. In one aspect, a method or process for making a hardened bone cement composite includes producing a cement paste 201217296 and placing the paste in an environment in which the paste is curable. In one embodiment, a method for preparing a bone cement paste comprises mixing a powder component with a solidified liquid component by a mixing machine (eg, agitation). For example, the powder component can include a calcium sulfate source and a calcium phosphate source. The mixture ° or 'calcium sulfate source and calcium phosphate source can be separate powders. In this case, the calcium sulfate source and the calcium phosphate source may first be combined to form a powder mixture prior to mixing with the solidifying liquid component. The aforementioned calcium sulfate source and calcium phosphate source may be tetracalcium phosphate (TTCP) and/or anhydrous calcium dicalcium phosphate (DCPA) powder. It should be noted that other types of sources may be used as long as they have similar chemical properties or characteristics as TTCP and/or DCPA. In one embodiment, the bone cement paste hardens or solidifies during the curing period in an atmosphere or environment surrounded by body fluids (e.g., blood). During operation, the operator or physician places the bone cement paste in the hole or cavity of the damaged bone via an incision via a suitable tool. For example, for orthopedic, spinal or root canal treatment, when the cement paste becomes or solidifies in situ into a hardened bone cement composite, the hardened bone cement can be treated by the subject for a certain period of time according to a predetermined bioresorption rate. Reabsorb. Depending on the application, in one embodiment, the bone cement paste can be formed into the stiffness of the bone cement composite prior to implanting the bone cement paste into the body of the subject to repair the damaged site (eg, bone or teeth). Block or semi-rigid block In one embodiment, the bone cement paste 201217296 can be shot into a bone hole or cavity or through a mold using an orthopedic paste delivery tool, such as the conventional medical instrument described in US 7,325,702 B2. Forming wherein the paste will form a hardened bone cement composite block. It should be noted that the orthopedic delivery tool is capable of continuously delivering the paste into the bone cavity until the bone cavity is filled. Depending on the application, if the powder component does not contain a suitable pore former, a sensitive mass of cement can be formed. For example, 'in order to discharge or remove a portion of the liquid from the paste' to lower the liquid/powder ratio of the paste, the dense block can be formed by pressurizing the bone cement paste in the mold before the paste is cured. In one aspect, the pressure applied to the paste in the mold is from about 1 MPa to 500 MPa', preferably from 100 MPa to 500 MPa. It is noted that the dense block has excellent compressive strength, Can be used as a medical implant. It should also be noted that 'the impregnated liquid is used to impregnate the rigid or solid dense mass of calcium phosphate cement for a predetermined period of time, so that compared to the block that has not been subjected to such impregnation treatment The total compressive strength of the resulting impregnated block is increased. In one embodiment 'the impregnation liquid is a phosphate-containing solution. Exemplary aqueous solutions may include, but are not limited to, (NH4)3p〇4, (NH4 2HP〇4, ΝΗ4Η2ρ〇4, Κ3Ρ〇4, Κ2ΗΡ〇4, ΚΗ2Ρ〇4, Na3P〇4, Na2HP04, NaH2P〇4 or Η3Ρ〇4. In one example, the phosphate in the phosphate-containing solution The concentration is from about 0.1 Torr to about 6 Torr, preferably from about 1 Torr to about 3 Torr. When the powder component of the bone cement formulation contains a pore former, the porous block is used as a tissue-engineered scaffold (tissue-engineered scaffold) ) by impregnating the molded block in an immersion liquid The agent is dissolved in the immersion liquid. The pore former can be removed from the molding block. The pore former can be added during the mixing of the powder component and the solidified liquid component, or can be added before the mold is placed in the mold. In the obtained paste, the immersion liquid may be, for example, 11 201217296 acidic aqueous solution, alkaline aqueous solution, physiological solution, organic solvent or substantially pure water. In one embodiment, the immersion liquid is the same as the above immersion liquid. In one embodiment, the immersion liquid is water. In one aspect, the porous block has a porosity of 50-90% by volume. In one embodiment, a dense block or a porous block prepared according to the bone cement formulation, The dense cells and porous blocks prepared by the present invention can be further broken by immersing them in a suspension of living cells or a growth factor and/or a solution of the drug in a living cell, a growth factor and/or a drug. Granulating materials for other medical applications. The following examples through experimental procedures are illustrative and are used to illustrate specific embodiments of the invention, however, The embodiments are not to be construed as limiting the embodiments of the present invention to the specific embodiments, but are to be construed as illustrative only. : Ferric acid four good DCPA: anhydrous acid-breaking di-about CSH: calcium sulfate hemihydrate WT: working time ST: curing time L/P ratio: liquid / powder ratio cs : house strength used in the symbol of the table 12 201217296 # : will The powder was mixed with the liquid for 2 minutes and no paste could be formed. *: After being removed from the mold (by mixing the powder with the liquid for 30 minutes), the hardened cement block collapsed and broke into powder when it was immersed in the Hanks solution for 1 day. form. *: After 1 day of immersion in Hanks' solution, the hardened cement block was broken (broken/broken, but not dispersed into a powder form). Preparation of TTCP powder The TTCP powder was prepared by the method proposed by Brown and Epstein of the National Bureau of Standards-A Physics and CAem/Wr less 6 (1965) 69A 12], from the application of pyroic acid #5 (Cii2: P2〇7) ( Sigma Chem. Co., St. Louis, MO, USA) was prepared by reacting with acid-breaking 13⁄4 (CaC03) (Katayama Chem. Co., Sakamoto, Tokyo). The TTCP powder was prepared by uniformly mixing Ca2P207 powder and CaC03 powder for 12 hours. The mixing ratio of the Ca2P207 powder to the CaC03 powder was 1:1.27 (weight ratio), and the powder mixture was heated to 1400 ° C to react the two powders to form TTCP. Preparation of TTCP/DCPA/CSH Composite Paste An appropriate amount of TTCP and DCPA powder were uniformly mixed in a ball mill, and then uniformly mixed with an appropriate amount of CSH powder. The resulting TTCP/DCPA/CSH mixed powder is uniformly mixed with a desired curing solution (for example, 0.6 M (NH 4 ) 2 HP 04 ) at a desired L/P ratio (for example, 0.28 cc/g) to form TTCP/DCPA/. CSH paste. 13 201217296 Chemicals for research Chemicals Chemical manufacturer's address Tetracalcium phosphate (TTCP) Ca4(P04)20 Homemade Taiwan anhydrous calcium phosphate (DCPA) CaHP04 ACROS US, New Jersey hemihydrate calcium sulfate (CSH) CaS04l/2H20 Showa 曰本, Tokyo acid-depleted hydrogen II (NH4) 2HP〇4 Showa 曰本, Tokyo acid dihydrogen II NH4H2PO4 Showa 曰本, Tokyo _ acid hydrogen dipotassium K2HPO4 Showa 曰本, Tokyo tartaric acid c2h2 (oh) 2 (cooh) 2 Katayama Japan, Osaka citric acid c6h8o7 Pantreac Spain, Basilon malic acid c2h3 (oh) (cooh) 2 Pantreac nano composite cement compressive strength test In order to determine the hardening cement CS, after mixing for 1 minute, under pressure For 1.4 Mpa, the cement paste was filled in a cylindrical stainless steel mold with a diameter of 6 mm and a depth of 12 mm for 30 minutes. After removal from the mold, the hardened cement sample was impregnated in a Hanks physiological solution maintained at 37 ° C and stirred daily to help maintain a uniform ion concentration. After the impregnation, the sample was removed from the solution for the CS test and the sample was still wet ("tested under wet conditions"). The 201217296 CS test was conducted using a benchtop mechanical tester (Shimadzu AG-10kNX, Tokyo, Japan) at a crosshead speed of 1.0 mm/min. The test method is according to the ASTM 451-99a method. Working time/cure time determination The working time of the cement paste is determined by the time after the cement paste is no longer working. The curing time of the cement paste was determined according to the standard method for tooth dish acid cement described in IS 1566. The cement was considered to cure when a 400 g weight loaded on a vicat needle having a 1 mm diameter tip could not form a noticeable circular mark on the surface of the cement. pH measurement The pH change in the early stage (during curing) was determined using a pH meter (Suntex Instruments SP2000, Taipei, Taiwan), and the pH meter was immediately immersed in the cement paste after the powder was mixed with the solidified liquid. The first reading is taken at j minutes after mixing. Continue the measurement until the paste hardens. The readings were taken every second until 3 minutes after mixing. The reading is then taken every 6 sec. The pH change of the Hanks solution in which the cement paste sample was impregnated was monitored using the same pH meter. After the powder was mixed with the solidified solution for 5 minutes, 2 g of the cement paste was taken out and immersed in 2 〇ml of a Hanks solution having a pH of 7 〇 5 for testing. The solution was maintained at 37 ° C throughout the test and was continuously agitated to help maintain the ion concentration of the solution uniform. Cytotoxicity test Cytotoxicity test according to ISO 10993-5. Use the extraction method. 15 201217296 NIH/3T3 fibroblasts (seeding density 5000/well) were pre-incubated for 24 hours in Dulbecco's Modified Essential Medium (DMEM) supplemented with bovine serum (10%) and PSF (1%). The extract was prepared by making the hardened cement paste at a ratio of 0.1 (g/ml) at 37. The medium was immersed for 24 hours, and then the liquid was collected by centrifugation. The extract was added to a 96-well microplate (100 μΐ/well) which had been incubated in a humidified atmosphere of 5% CO 2 at 37 ° C. After 24 hours, the extract was aspirated and the medium was subsequently taken (1〇). A mixture of 〇μι) and WST-1 (10 μΐ) was added to the wells and incubated for 1 hour at 371:. The WST-1 sample was used to determine cell viability. This is a colorimetric assay of mitochondrial dehydrogenase activity&apos; where the absorbance at 450 nm is proportional to the dehydrogenase activity in the cell. One hour after incubation, the mixture of medium and WST-1 was transferred to a 96-well microplate and the absorbance at 450 nm was determined using an ELISA reader. Ai2o3 powder was also tested as a control. Test 4 times for each sample ("=4"). Cell line information

Cell name NIH/3T3 Cell number BCRC 60008 Type mouse NIH/Swiss embryo growth performance adherent (adherent), 5% C02, 37 °C Morphology fibroblast cell culture medium 90% Dulbecco Modified Eagle medium (DMEM) + 10% small Ox ok clear (cs) Freezing medium 93% medium + 7% DMSO 201217296 Control 1: TTCP/CSH cement and (nh4) 2hpo4 curing solution Table 1: TTCP/CSH TTCP/CSH mixed with 0.25-0.75M (NH4)2HP04 (weight ratio) (NH4)2HP〇4 Concentration (μ) L/P ratio (cc/g) WT (minutes) ST (minutes) ld-CS (MPa) 0.28 - - 氺0.25 0.33 - * 0.35 ※ 0.28 7.4 Soil 0.6 9.0 ± 0.7 3.23 ± 0.53 0.50 0.33 10.3 ± 0.6 11.6 Soil 0.5 2.33 ± 0.56 90/10 0.35 11.0 ± 0.3 12.9 ± 0.2 2.40 ± 0.71 0.28 7.0 ± 0.3 8.5 ± 0.5 3.67 Soil 0.49 0.60 0.33 10.1 ± 0.5 11.5 ± 0.6 3.06 ±0.44 0.35 11.9 Soil 0.6 13.0±0.7 3.56 Soil 0.74 0.28 5.8 ± 0.2 7.1 ± 0.5 4.07 ± 1.02 0.75 0.33 8.9 Soil 0_1 11.0 ± 0.2 4.84 ± 0.59 0.35 10.4 ± 0.5 12.2 ± 0.2 3.74 ± 0.19 0.28 - * 75/25 0.25 0.33 氺0.35 氺0.28 7.5± 0.3 10.1±0.2 4.32±0.11 0.50 0.33 9.7 ± 0.3 11.7±0.3 7.01±0.42 0.35 10.7 Soil 0.3 12.5 ± 0.4 7.32±0.38 17 201217296 0.28 6·5 ± 0.3 8.2 ± 0.2 5.92 ± 0.42 0.60 0.33 7.1 ± 0.3 9.1 ± 0.3 7.63 ± 0.28 0.35 9.0 ± 0.2 10_4 Soil 0.1 8.32 ± 0.31 0.28 6.4 ± 0.2 8.0 ± 0.1 6.64 ± 0.52 0.75 0.33 7.5 ± 0.3 9.0 ± 0.4 9.55 ± 0.25 0.35 8.3 Soil 0.3 9.9 ± 0.3 10.36 ± 0.27 0.28 - 氺 0.25 0.33 0.35 氺0.28 7.1±0.3 9.8±0.3 3.37±0.27 0.50 0.33 9.2±0.2 11.1 ± 0.3 5.84±0.37 65/35 0.35 10.5±0.3 12.2±0.4 6.10±0.26 0.28 4.5±0.4 5.3±0.2 3.96±0.12 0.60 0.33 7.0± 0.3 9.0±0.4 5.44±0.14 0.35 8.9±0.4 9.8±0.3 6.56±0.12 0.28 6.3±0.2 7.8±0.2 4.41±0.24 0.75 0.33 7.1±0.2 8.4±0.3 6.43±0.27 0.35 8.2 ±0.3 9.3 Soil 0.2 7.55 Soil 0.34 In use In the case of 0.25 M (NH4)2HP04 preparation paste, the molding block collapses and ruptures (*) when immersed in Hanks solution, or the compressive strength cannot be measured after 1 day of immersion in Hanks solution), as shown in Table 1 is shown. As for the paste prepared using the higher concentration (Nh4)2HP〇4 solidified solution, the hardened cement block had a very low compressive strength after being immersed in the Hanks solution for 1 day (ld_cs) as shown in Table 1. Obviously, only the 18 201217296 powder component having the TTCP and CSH phases did not give satisfactory results.

Control 2: TTCP/CSH cement and ΝΗ4Η2Ρ04 curing solution Table 2: TTCP/CSH TTCP/CSH NH4H2PO4 L/P ratio mixed with 0.25-0.75M NH4H2P〇4 WT ST ld-CS (weight ratio) Concentration (M) (cc /g) (minutes) (minutes) (MPa) 0.28 - 氺0.25 0.33 - - 氺0.35 - 氺0.28 7.4 ± 0.6 9.0 ± 0.7 3.23 ± 0.53 0.50 0.33 10.3 ± 0.6 11.6 Soil 0.5 2.33 ± 0.56 90/10 0.35 11.0 ± 0.3 12.9±0.2 2.40±0.71 0.28 7.0±0.3 8_5 Soil 0.5 3.67 ± 0.49 0.60 0.33 10.1±0.5 11.5±0.6 3.06 ± 0.44 0.35 11.9 ± 0.4 13.0 ± 0.7 3.56 ± 0.74 0.28 5.8 Soil 0.2 7.1 Soil 0.5 4.07 Soil 1.02 0.75 0.33 8.9±0.1 11. ±0.2 4.91 Soil 0.66 0.35 10.4 Soil 0.5 12.12±0.2 3.74 ± 0.19 0.28 - - * 75/25 0.25 0.33 - - * 0.35 - - 氺0.28 - - 氺0.50 0.33 - 氺0.35 - * 19 201217296 0.28 - 0.60 0.33 - 氺0.35 - 0.28 氺0.75 0.33 - ♦ 0.35 - - 0.28 - - 氺0.25 0.33 - * 0.35 - - ♦ 0.28 He 0.50 0.33 * 0.35 - 氺65/35 0.28 - _ 氺0.60 0.33 - - * 0.35 - 氺0.28 - - 0.75 0.33 - - 氺0.35 - 氺 Table 2 shows that the NH4H2P〇4 curing solution used for Control 2 does not improve the working time/cure time of the (NH4)2HP04 curing solution for Control 1 and ld-CS. Obviously, only the powder component having the TTCP and CSH phases did not give satisfactory results. Control 3: DCPA/CSH cement and (Nh4)2HP〇4 solid solution 20 201217296 Table 3: DCPA/CSH DCPA/CSH (NH4)2HP〇4 L/P ratio mixed with 0.25-0.75M (NH4)2HP〇4 WT ST ld-CS (weight ratio) Concentration (μ) (cc/g) (minutes) (minutes) (MPa) 0.28 - * 0.25 0.33 - - This 0.35 - - This 0.28 - - 0.50 0.33 - ※ 90/10 0.35 - ※ 0.28 - 0.60 0.33 - - ※ 0.35 - - ※ 0.28 - - 0.75 0.33 Where - ※ 0.35 ※ 0.28 - ※ 75/25 0.25 0.33 - - ※ 0.35 - - ※ 0.28 ※ 0.50 0.33 - ※ 0.35 - - ※ 0.28 - ※ 0.60 0.33 - - ※ 0.35 - - ※ 21 201217296

The Hanks solution collapsed and ruptured (*)' or their compressive strength could not be measured after 1 day of immersion in the Hanks solution φ 1 ,*), as shown in Table 3. Obviously, only the powder component having the DCPA and CSH phases did not give satisfactory results.

Control 4: DCPA/CSH cement and νΗ4Η2Ρ04 solidified solution Table 4: DCPA/CSH 22 mixed with 0.25-0.75Μ ΝΗ4Η2Ρ〇4 201217296 DCPA/CSH NH4H2P〇4 L/P ratio WT ST ld-CS (weight ratio) Concentration ( () (cc) (0.25) - - ※ 0.28 - ※ 0.75 0.33 - - ※ 0.35 - - ※ 0.28 ※ 75/25 0.25 0.33 _ 0.35 - ※ 0.28 - - ※ 0.50 0.33 - ※ 0.35 - - ※ 0.28 - - ※ 0.60 0.33 - - ※ 0.35 - - ※ 23 201217296 0.28 - ※ 0.75 0.33 - ※ 0.35 ※ 0.28 - - ※ 0.25 0.33 ※ 0.35 - - ※ 0.28 - - ※ 0.50 0.33 - ※ 65/35 0.35 - - ※ 0.28 - ※ 0.60 0.33 - ※ 0.35 ※ 0.28 - ※ 0.75 0.33 - * 0.35 ※ The compressive strength of molded parts prepared from DCPA/CSH cement after 1 day of immersion in Hanks solution cannot be measured (※ 丨, as shown in Table 4. Obviously, only DCPA and CSH phases are present. The final component did not give satisfactory results. 0 24 201217296 TTCP/DCPA: CSH (weight ratio) in Table 5-14 TTCP: DCPA: CSH (weight ratio) 90:10 2.69:1:0.41 85:15 · 2.69 :1:0.65 80:20 2.69:1:0.92 75:25 2.69:1:1.23 65:35 2.69:1:1.99 55:45 2.69:1:3.02 45:55 2.69:1:4.51 35:65 2.69:1 :6.85 25:75 2.69:1:11.07 10:90 2.69:1:33.21 Note: Under all conditions, the molar ratio of TTCP to DCPA is 1:1 25 201217296 Example 1: (TTCP/DCPA)/CSH cement and Various curing solutions Table 5: 75 wt% phosphate (TTCP/DCPA) / 25 wt% CSH composite cement solid solution concentration (M) solution pH WT (minutes) ST (minutes) ld-CS (MPa) 1 9.27 1.53 ± 0.21 2.72 ± 0.26 15.35 ± 0.85 K2HP 〇 4 0.75 9.20 1.88 Soil 0.13 3.08 ± 0.15 15.46 ± 3.51 (L / P = 0.33) 0.5 9.17 2.85 ± 0.13 3.93 ± 0.16 18.39 ± 1.53 0.25 9.15 — — 24.12 ± 6.30 1 8.17 4.88 ± 0.13 6.93 ± 0.25 27.77 ± 1.6 (NH4) 2HP 〇 4 0.75 8.09 5.47 ± 0.13 7.45 ± 0.16 25.37 ± 0.69 (L / P = 0.33) 0.6 7.97 5.77 ± 0.13 7.53 ± 0.27 41.02 ± 3.77 0.5 7.95 7.85 ± 0.32 10.05 Soil 0.33 21. 58±1.82 0.25 7.92 13.5±0.5 16·28±1.1 This 1 3.96 4.95±0.5 7.5 ±0.5 * (NH4)H2P〇4 0.75 3.99 6.63±0.38 8.93±0.33 ♦ (L/P=033) 0.5 4.28 9.43±0.416 12.6 Soil 0.53 * 0.25 4.30 11.42 ± 0.5 15.18 ± 0.27 氺 1 3.89 6.5 ± 0.43 9 ± 0.33 23.82 ± 3.23 NaH2P04.2H20 0.75 3.97 8.05 ± 0.25 11.05 ± 0.75 18.96 ± 1. 79 (L / P = 0.33) 0.5 4.13 10.72 ±0.25 14.68±0.28 0.25 4.22 12.92±0.67 16.16±1.03 * The data shown in Table 5 can be summarized as follows: 1. The WT/ST of k2hpo4-derived hardened cement composite is too short and CS is low. 2. The (NH4)H2P04-derived hardened cement composite has a reasonable WT/ST, but is dispersed after being immersed in Hanks' solution. 26 201217296 3, NaH2P04 2H20-derived hardened cement composite has reasonable WT/ST, but the acidity is too strong and the strength is low. 4. (NH4)2HP04 produced the highest CS ° 5 in all tested solidified solutions, and the highest CS (41 MPa) was obtained at 0.6 Μ in all (NH4)2HP〇4 concentrations.

Example 2: TTCP/DCPA/CSH mixed with 0.60M (NH4)2HP04 Table 6: TTCP/DCPA/CSH rrCP/DCPA mixed with 0.60M(NH4)2HP〇4: CSH (weight ratio) Curing solution L/ P ratio (cc/g) ld-CS (MPa) WT/ST (minutes) Cytotoxicity OD (%) (Α12〇3 as control-100%) 90:10 0.60 Μ (ΝΗ4)2ΗΡ〇4 0.28 45.10± 3.50 6.1±0.1/ 7.1±0.1 ---- 86.40±2.2〇85:15 0.60 Μ (ΝΗ4)2ΗΡ〇4 0.28 44.50±5.50 5.8±0.1/ 6.9±0.2 — 91.76±4.9〇80:20 0.60 Μ (ΝΗ4 ) 2ΗΡ〇4 0.28 40.93±3.98 6·6 Soil 0·3/ 7·7 Soil 0·3 ----- 89.32±〇.28 75:25 0.60 Μ (ΝΗ4)2ΗΡ〇4 0.28 40.45±2.39 5.8± 0.1/ 7.5±〇.3 ----- 95.49±3.〇4 65:35 0.60 Μ (ΝΗ4)2ΗΡ〇4 0.28 26.53 soil 1.57 5.5±0.3/ 7.5±0·4 —— 84.94±2.98 55:45 0.60 Μ (ΝΗ4)2ΗΡ〇4 0.28 28.07±1.54 5·2 Soil 0.2/ 6·8 士0·3 ------ 101.99±〇.74 45:55 0.60 Μ (ΝΗ4)2ΗΡ〇4 0.28 27.02 1_29 5.5 ± 0.2 / 6 · 9 ± 0 · 1 ----- 89.29 ± 1 〇 . 44 -- 27 201217296 35:65 0.60 Μ (ΝΉ 4) 2 ΗΡ〇 4 0.28 14.10 ± 3.10 4.4 ± 0 · 3 / 6.4 ± 0.4 97.31±1.91 25 :75 0.60 Μ (νη4)2ηρο4 0.28 13.80±1.61 5.1±0.1/ 6.1±0·4 85.97±3.94 10:90 0.60 Μ (νη4)2ηρο4 0.28 9·77±1·15 5.0±0.2/ 7.9±0.2 93.17 8.63 Summary of the results shown in Table 6 (TTCP/DCPA/CSH mixed with 0.60M (NH4)2HP〇4): (1) When the CSH content in TTCP/DCPA/CSH cement powder is higher than about 65 wt% At this time, its CS value becomes too low (&lt;15 MPa). Under the conditions tested, the appropriate CSH content should be less than about 65% by weight. In order to achieve higher strength (CS &gt; 30 MPa), the CSH content should be less than about 35 weight. /〇. (2) When 0.60 M (NH4)2HP04 is used as the hardening solution, all cytotoxicity values are acceptably greater than 80% for all CSH contents (from about 10% by weight to about 90% by weight). 28 201217296

Example 3: TTCP/DCPA/CSH mixed with 0.20-3.0 M (NH4)2HP〇4

Table 7: TTCP/DCPA/CSH mixed with 0.20-3.00M (NH4)2HP〇4 (TTCP/DCPA: CSH = 90:10) Powder (NH4)2HP〇4 Concentration (Μ) L/P ratio (cc/ g) ld-CS (MPa) WT/ST (minutes) cytotoxicity OD (%) (ai2o3 as control - 100%) TTCP/DCPA: CSH (90:10) 0.20 0.28 wood - 0.25 0.28 * 8.1 ± 0.2/ 9.9±0.2 ----- 104.95±6.46 0.50 0.28 32.37±3.10 5.9 Soil 0.3/ 7.2±0·7 91.31±5.77 0.60 0.28 45.11±3.50 6.1±0.2/ 7.1±0.1 91.61±6.06 0.75 0.28 35.48±1.8 5.9 士士0.3/ 6·9±0·2 86.99±5.13 1.00 0.28 35.79±2.60 5.7±0.1/ 6.3±0.1 ------ 74.09±3.44 2.00 0.28 41.75 Earth 2.60 4.5±0.5/ 5.9 Soil 0.3 57.85±4.22 3.00 0.28 42.68±2.60 4·7 ± 0.2/6·0±0·1 46.80±5.04 In Table 7 (TTCP/DCPA/CSH mixed with 0.20-3.00M (NH4)2HP〇4 (TTCP/DCPA: CSH = 90: Summary of results shown in 10)) (1) When the concentration of (NH4)2HP〇4 is too low (under the current test conditions, 0.25 29 201217296 Μ or lower), when the hardened paste is impregnated in Hanks' solution Dispersed and its strength cannot be measured. (2) Although ammonium is a key life support element, the concentration of (NH4)2HP04 should not be too high (2 Μ or higher under current test conditions) in order to reduce the cytotoxicity level. (3) The appropriate concentration of (ΝΗ4)2ΗΡ04 should be 0.25 Μ-2.0 Μ, preferably 0.5 Μ-1.0 Μ. (Or ΝΗ4 + ion concentration is 0.50 Μ-4.0 Μ, preferably 1.0 Μ-2.0 Μ).

Example 4: TTCP/DCPA/CSH mixed with 0.20-3.0 Μ (ΝΗ4) 2ΗΡ〇4 Table 8: TTCP/DCPA/CSH mixed with 0.20-3.00Μ(ΝΗ4)2ΗΡ〇4 (TTCP/DCPA: CSH = 75:25) Powder (NH4)2HP〇4 Concentration (μ) L/P ratio (cc/g) ld-CS (MPa) WT/ST (minutes) Cytotoxicity 〇.D. (%) (ai2o3 as a control -l〇〇%&gt; TTCP/DCPA:CSH (75:25) 0.20 0.28 * - 0.25 0.28 氺13.5±0.5/ 16.3 ±1.1 98.94±3,41 0.50 0.28 21·58±1·82 7.9±0.3/ 10.1 ± 0.3 90.83±6.02 0.60 0.28 40.45±2.39 5.8±0.1/ 7.5±0.3 88.17±1.39 30 201217296 0.75 0.28 25·37 ±0.69 5.5 Soil 0.1/ 7.5 ±0.2 93.32±5.01 1.00 0.28 27.77±1.60 4.9±0.1/ 6.9 士0.3 91.21 ± 1.99 2.00 0.28 24.53 ± 1.80 3.6 ± 0.5 / 4.8 ± 0.3 74.42 ± 3.25 3.00 0.28 32.86 ± 2.10 2.9 ± 0.1 / 4.2 ± 0.3 59.79 ± 3.23 in Table 8 (mixed with 0.20-3.00M (NH4) 2HP 〇 4 Summary of the results shown in TTCP/DCPA/CSH (TTCP/DCPA: CSH = 75:25): (1) When the concentration of (NH4)2HP〇4 is too low (under current test conditions, 〇25 Μ or more) Low) when the hardened paste is dispersed in the Hanks solution, and its Degree can not be measured. 'But in order to reduce the fineness (in the current test conditions (2), although it is the critical cytotoxicity level of the life-supporting building elements, (ΝΗ4) 2ΗΡ04 concentration can not be too low, &gt; 2 M) » 2·〇 Μ, preferably Μ-4·〇μ, excellent (3) The appropriate concentration of (NH4)2HP04 should be 〇.25m for 0.5 Μ·1.〇Μ (or NH4+ ion concentration is 〇5〇 selected as 1.0 M-2.0 M).

Example 5: TTCP/DCPA/CSH 31 mixed with 0.25-1.0 Μ (ΝΗ4) 2ΗΡ04 201217296

Table 9: TTCP/DCPA/CSH mixed with 0.25-1.0M (NH4)2HP〇4 (TTCP/DCPA: CSH = 65:35) Powder (NH4)2HP04 Concentrated L/P 1-d CS Degree (Μ) ( Cc/g) (MPa) 0.35 21.24 Soil 1.82 0.33 23.12±1.21 1.00 0.30 23.33±1.38 0.28 23.52±1.67 0.35 24.32 ± 1.56 0.33 25.62 Soil 0.93 0.75 0.30 24.36 ±1·62 0.28 29.54±1.13 0.35 18.36 Earth 1.45 0.33 22.59 Earth 1.61 0.50 0.30 26.75 ± 1.51 TTCP/DCPA: CSH 0.28 31.37 ± 0.81 (65:35) 0.35 34.23±0·61 0.33 30.77±1·57 0.45 0.30 25.01 Soil 0.56 0.28 22.65 Soil 1.23 0.35 27.32 Soil 1.45 0.3 3 32.51±0.72 0.40 0.30 28.77±1.22 0.28 14.16 ± 1.15 0.35 氺 0.33 * 0.25 0.30 This 0.28 * 32 201217296 In Table 9 (TTCP/DCPA/CSH mixed with 0.25-1.0M (NH4)2HP〇4 (TTCP/DCPA: CSH = 65 Summary of the results shown in :35)): (1) When the concentration of (NH4)2HP04 is too low (0.25M or less under the current test conditions), the hardened paste is dispersed in the Hanks solution, and its The strength cannot be measured.

(2) With the exception of a few cases, all 1-d CS values are higher than 20 MPa and, in some cases, above 30 Mpa. Example 6: TTCP/DCPA/CSH mixed with 0·40-1·0 Μ (ΝΗ4) 2ΗΡ04 Table 10: TTCP/DCPA/CSH mixed with 0.40-1·00Μ(ΝΗ4)2ΗΡΟ4 (TTCP/DCPA: CSH = 55:45) Powder (NH4)2HP〇4 Concentration (Μ) L/P ratio (cc/g) WT (minutes) ST (minutes) 1-d CS (MPa) TTCP/DCPA: CSH 0.35 10.3±0.3 11.9 ±0.1 28.87±2.52 (55:45) 0.40 0.33 9.3±0.3~ 10.9±0.2 30.46±1.89 0.30 7.9±0.5 9.4±〇.3 26.62±2.23 0.28 6.9±0.4 8.6±0.2 24.96±3.79 0.35 8.9±0.1 10.8± 0.2 27.93±2.69 0.45 0.33 7.7±0.3 9.6±0.2 26.22±2.51 0.30 6.6±0.2 8.5±0.3 26.71±1.41 0.28 5.4 ±0.4 7.4±0.4 27.82±2.59 33 201217296 0.35 9.2±0.1 11.2±0.2 24.67±2.23 0.33 8.4± 0_3 10.3士士 0.2 27.86土2.26 0.50 0.30 7.2±0.2 9.2±〇.3 32.05±3.02 0.28 6.0±0.3 7.5±0.3 34.70±1.52 0.26 5.4±0.2 7.4±0.1 30.50±3.77 0.35 8·5 Soil 0·3 10.3± 0.3 28.60±1.99 0.60 0.33 7.3±0.3 9.2 ± 0.2 27.10±1.28 0.3 6·3 ± 0.1 8.4 ± 0.1 25.74 ± 2.20 0.28 5.2 Soil 0_2 6.8 ± 0.3 28.07 ± 1.54 0.35 6.4 ± 0.4 8.5 ± .2 23.40±3.55 0.75 0.33 5.3 ± 0.3 ± 0.4 29.25 ± 1.45 0.30 5.2 ± 0.3 7.1 Soil 0.2 29.59 ± 2.65 0.28 4.7 ± 0.3 6.5 ± 0.3 30.00 ± 2.83 0.35 5.3 ± 0.1 7.0 ± 0.2 28.46 ± 3.38 1.00 0.33 4.5 0.2 6.2±0.2 30.7U2.76 0.30 3.7±0.3 5.3±0.1 25.71±3.86 0.28 2.9±0.3 4.2 Soil 0.3 29.58 ± 1.24 In Table 10 (Ding 1^/〇 mixed with 0.40-1.00M (NH4)2HP〇4 The results shown in 0?8/€811 (1'1^/〇€卩8:匚811 = 55:45)) are summarized as follows: (1) All 1-d CS values are higher than 20 MPa, and, at some Under these conditions, it is higher than 30 MPa. (2) For higher concentrations (1·0Μ) and lower L/P values (less than 0.33 cc/g), WT/ST is a bit too short. 34 201217296

Example 7: TTCP/DCPA/CSH mixed with 0.40-0.60 M (NH4)2HP〇4

Table 11: TTCP/DCPA/CSH mixed with 0.40-0.60 M (NH4)2HP04 (TTCP/DCPA: CSH = 45:55) Powder (nh4) 2hpo4 Concentration (Μ) L/P ratio (cc/g) WT ( Minutes) ST (minutes) 1-dCS (MPa) 0.35 8.2 ± 0.3 10.7 Soil 0.2 21.1 ± 1.0 0.40 0.33 7.5 ± 0.2 9.6 ± 0.3 23.3 ± 2.0 0.30 6.1 ± 0.3 8.3 ± 0.2 27.1 Soil 2.2 rrCP/DCPA: CSH (45 :55) 0.35 7.6±0.3 10.2 ± 0.2 22.3±0.5 0.50 0.33 7.0±0.5 9.1±0.2 22.1 ± 2.2 0.30 5.8 ± 0.2 7.8 Soil 0.1 24.1 Soil 1.6 0.35 7.9 ± 0.3 10.0 ± 0.2 21.4 ± 2.0 0.60 0.33 6.6 ± 0.4 9.0 ±0.6 23.8±1.7 0.30 5.5 ± 0.1 7.5 ± 0.2 23.8 ± 1.7 In Table 11 (TTCP/DCPA/CSH (TTCP/DCPA: CSH = 45:55) mixed with 0.40-0.60M (NH4)2HP〇4) The results are summarized as follows: (1) All 1-d CS values are higher than 20 Mpa. (2) Under all test conditions, the working time is longer than 5.5 minutes and the curing time is longer than 7.5 minutes. 35 201217296 (cddw) sus Ksu/vdua/dull Alkali ¥^Εκ-^^ψ趄绂s5l§ffi^fNI&lt; U-Os rn On Pi m in IT) m ON ro a\ ro CN +1 &lt;N m Os yn CN 龙CN so oo Xfl U 1 T3 〇〇&lt;N 卜fH rn inch a\ m oo 'O CO (N to m &gt;n VO r〇VO VO fTMH -H cs CN CS 屮KM U Inch v〇0Λ inch· oo m CN CO rn oo m 〇\ inch· Bu »nm in CN +1 m oo m r&quot;H &lt;N Λ 00 inch · K/l U ni 卜 rn +1 o CN v〇思CN 〇rn m ζ inch OO m yn CN mc^ Λ o Xfl U &quot;ύ m oo inch · Λ in 〇m (N inch · »n inch inch TH to τ·Η Pi in (N rn »n cs cK m tn i 1 time v〇ro mot-H l〇On C/} U 1 T3 rH ro t&gt; io vo o Os m rj jn o S o CO CN 芝 〇 od CN s- oo CN 〇oo ( N o oo CN 〇oo &lt;N 〇m 〇m 〇轶s 13⁄4 W (N ^ 3 °I li O &lt;N ^ 3 °I li O cs °I |S sgg °i 13⁄4 Ο (N ^ 3 ° IX (Λ U ♦! ^ Φ1 &amp; H '^ HH 〇&lt;nt-H &gt;n 00 (N yn rn »〇jn Cn U^i 201217296 Summary of the results shown in Table 12: (1) In addition to Outside the "55:45" composite, all 42d-CS values are higher than 20 M: Pa 'This shows that the strength is only mildly reduced even after 42 days of immersion in Hanks' solution. However, when the CSH content is increased to 45% by weight, the CS value of the composite material drops very significantly. Example 8: Addition of organic acids Effect on TTCP/DCPA/CSH mixed with i.om (NH4)2HP04 Table 13: Addition of organic acids (tartaric acid, citric acid and malic acid) to TTCP/DCPA/CSH mixed with 1 Μ (ΝΗ4) 2ΗΡ04 ( Effect of TTCP/DCPA: CSH = 75:25) Performance of Organic Acids Organic Acids L/P Ratio Solution WT ST ld-CS (M) (cc/g) pH (minutes) (minutes) (MPa) 0.4 0.40 5.31 7.8 ±0.2 9.9 ±0.4 20.17±2·20 Malic acid 0.3 0.40 5.86 8.4 ±0.4 10.5±0.5 24.15±2.73 0.2 0.40 6.39 9.0±0.5 10.50±0.5 23.44±3.79 0.1 0.40 6.98 9.4 ±0.4 10.4 ± 0.5 23.90±3.05 0.4 0.33 4.71 2.4 ±0.3 4.0 ±0.3 27.65±3.24 Citric acid 0.3 0.33 5.28 4.7±0.6 7.1 ±0.1 30.08±1.44 0.2 0.33 5.94 7.0±0.3 10.0±0.4 29.48±1.46 0.1 0.33 6.71 9.2±0.4 10.3 ±0.4 31.66±2.49 0.4 0.33 5.10 3.9 ±0.3 6.8 ± 0.2 32.38 soil 2.48 tartaric acid 0.35 0.33 5.57 4.2 ± 0.2 7.1 ±0.1 34.60±3.70 0.3 0.33 5.62 6.0 ±0.5 9.8 ±0.2 30.97±2.86 37 201217296 0.2 0.33 6.25 7.2±0.4 10.2 ±0.4 26.04±3.64 0.1 0.33 6.99 9.4±0.4 11.2 Soil 0.2 27.36±5.31 In Table 13 The results are summarized as follows: (1) Adding malic acid to the 1 M (NH4)2HP04 solidified solution reduces the CS value of the hardened composite cement. (2) Adding citric acid to the 1 M (NH4)2HP〇4 solidification solution increases the CS value of the hardened composite cement (from about 28 MPa to about 32 MPa). (3) Adding tartaric acid to the 1 M (NH4)2HP04 solidified solution to increase the CS value of the hardened composite cement (from about 28 MPa to 35 MPa). Preparation of TTCP/DCPA/CSH Composite Dense Blocks An appropriate amount of TTCP and DCPA powder were uniformly mixed in a ball mill and then uniformly mixed with an appropriate amount of CSH powder. The obtained TTCP/DCPA/CSH mixed powder is uniformly mixed with a desired solidified solution (for example, 0.6 M (NH 4 ) 2 HP 〇 4 ) at a desired L/P ratio (for example, 0.28 cc / g) to form TTCP / DCPA/CSH paste. Prior to complete hardening, the paste is placed in a mold at a desired pressure (maximum pressure of 150, 300 or 450 Kgf) to squeeze a portion of the liquid out of the paste. After removal from the mold, a set of hardened composite samples were placed in a moisture barrier container for 1 day. Another set of samples was re-impregnated for 1 day in an impregnation solution (1M (NH4)2HP〇4 or 1M K2HP〇4) maintained at the desired temperature (37 °C), followed by an oven at 50 °C. Dry for 1 day. 38 201217296 Preparation of TTCP/DCPA/CSH composite porous block An appropriate amount of TTCP and DCPA powder were uniformly mixed in a ball mill, and then uniformly mixed with an appropriate amount of CSH powder. The obtained TTCP/DCPA/CSH mixed powder is uniformly mixed with a desired solidified solution (for example, 0.6 M (NH 4 ) 2 HP 04 ) at a desired L/P ratio (for example, 0, 28 cc / g) to form TTCP / DCPA/CSH paste. The composite paste is then uniformly mixed with a pore forming agent (for example, KC1 particles) in a desired weight ratio (for example, TTCP/DCPA/CSH: KC1 = 1:1 or 1:2) to form TTCP/DCPA/CSH/ KC1 paste. Prior to complete hardening, the composite paste was placed in a mold at a desired pressure (maximum pressure of 450 Kgf) to squeeze a portion of the liquid out of the paste. After removal from the mold, a set of hardened composite blocks were immersed in deionized water at 37 ° C for 3 days to dissolve the KC1 particles to form a porous composite block, which was then dried in a 50 t oven for 1 day. Another set of samples was re-impregnated for one day in an impregnation solution (eg, 1 M (NH4) 2 HP04 or 1 M K2 HP04) maintained at the desired temperature (37 ° C) to increase the strength of the porous mass, followed by 50 Dry in an oven at °C for 1 day. In order to remove the residual impregnation solution from the inside of the well, the impregnated porous sample was further rinsed for 3 days in deionized water at 37 °C. Porosity Determination according to ASTM C830-00 (2006) “Standard Test Methods for Apparent Porosity, Liquid Absorption, Apparent Specific Gravity, and Bulk Density of Refractory Shapes by 39 201217296

Vacuum Pressure (Standard Test Method for Apparent Porosity, Liquid Absorption, Apparent Specific Gravity, and Bulk Density of Refractory Profiles by Vacuum Pressure)" The porosity of each sample was determined. Example 9: Dense Blocks Table 14: Compressive strength (MPa) of TTCP/DCPA/CSH composite dense block prepared from TTCP/DCPA/CSH mixed powder mixed with 0.6M(NH4)2HPO4 (L/P=0.28cc/g) TTCP/DCPA: CSH (weight 1) impregnation in 1 Μ (NH4)2HP〇4 at 37 ° C for 1 day without immersion in 1 M K2HPO 4 at 37 ° C. Molding pressure (kgf) Molding pressure (kgf) Molding Pressure (kgf) 150 300 450 150 300 450 150 300 450 42.74 49.21 55.86 101.38 130.83 167.02 111.07 162.96 160.07 90:10 ±3.20 ±3.17 ±1.67 ±9.23 ±6.88 ±7.57 ±6.93 ±8.07 ±4.13 38.11 49.21 53.55 100.26 127.49 162.95 105.78 142.01 150.07 85:15 ±2.51 ±3.69 ±1.14 Soil 7.06 ±11.21 ±6.26 ±6.81 ±8.92 ±3.25 38.02 46.34 54.78 103.07 121.68 137.99 105.32 129.10 144.90 75:25 ±3.00 ±1.79 ±7.45 ±6.55 Soil 5.07 ±9.58 ±7.02 ± 9.81 ±11.33 36.14 46.32 60.64 101.04 120.53 134.78 98.26 131.78 136.85 65:35 ±1·64 ±8.16 ± 2.34 ±4.77 ±7.98 ±9.74 ±10.71 ±6.77 Earth 8.47 35.59 48.71 54.95 95.14 121.91 128.63 90.18 132.57 140.37 55:45 ±1.32 ±2.80 Earth 4.70 ±6,06 ±7.68 ±6.92 ±3.63 ±5.28 ±3.45 40 201217296 Summary of the results shown in Table 14 (Compressive Strength of TTCP/DCPA/CSH Composite Dense Blocks): (1) Under all conditions, dip The collapsed-treated sample has a significantly higher CS value. (2) Under all conditions, the CS value increases significantly as the molding pressure increases. Example 10: Porous block Table 15: TTCP/DCPA/CSH prepared from a mixed powder of TTCP/DCPA/CSH/KC1 (porogen) mixed with 0.6M(NH4)2HPO4 (L/P = 0.33 cc/g) Porosity value (volume %) of composite porous block TTCP/DCPA: CSH (weight ratio) TTCP/DCPA/CSH: KC1 = 1:1 (weight ratio) TTCP/DCPA/CSH: KC1 = 1:2 (weight ratio) 90:10 46.02 Soil 2.87 81.51 ±6.57 85:15 57.66± 0.98 83.77 ±5.61 75:25 59.82 ±1.16 84.32 ±6.71 65:35 63.02 ±1.41 87.86 ±3.74 55:45 59.98 ±0.87 88.69 ±5.72 In Table 15 ( The results shown in the TTCF7DCPA/CSH composite porous block prepared from a mixed powder of TTCP/DCPA/CSH/KC1 (porogen) mixed with 0.6 M (NH4)2HP〇4 are summarized: (1) in TTCP/DCPA /CSH: KC1 = 1:1, the porosity value is 41 201217296 46-63%, and when TTCP/DCPA/CSH: KC1 = 1:2, the porosity value is 81-8 9%, which is ideally Used as a tissue-engineering scaffold. (2) As the CSH content in the composite increases, the porosity value generally increases. 42 201217296 #φ^(ί#^?οιυ:χ/:Η8υ/ν(1Ηυα/ΡΗυΙΗ^φ^(&amp;οοο££.ο=&Η/Ί)·&lt;ΐο&lt;ϋ(inch H£ lAt9.0 Disc·®: 9Ι&lt; 1K vs ds)_娥紫ws^_Jtv呤实龙HSu/vdua/duHl 容架铋&lt; immersed in 1Μ k2hpo4 at 37°C for 1 day TTCP/DCPA/CSH: KC1 = 1:2 (weight ratio) 1.50±0·30 1.36±0.19 0.93±0.23 0.87±0_09 0.64±0.07 Immersion in 1M k2hpo4 at 37 °C for 1 day TTCP/DCPA/CSH: KC1= 1:1 ( Weight ratio) 8.71±0.93 7.37±〇.98 7.40 Soil 0_73 5.15±0.70 4.55±0.33 * * S? , ^ ii u S &lt; δ Λ _ K ffi - Q u ΦΗ m X Pi ^ W ^ 1 H 1.62± 0.28 1.22±0.19 0.98±0.18 0.91±0.05 0.71±0.10 ^ d ^ V £ 〇a: ^ υ Λ ®H t- ffi ^ $ U vW IS 8.43±0.73 7.29±0.54 7.03 Soil 0.49 5.19±0.26 4.01±0.56 Dipping TTCP/DCPA/CSH: KC1= 1:2 (weight ratio) 0.92 ±0.18 0.82 ± 0.23 0.74 ±0.10 0.51 ±0.07 0.42 ± 0.06 ffi m ί 〇Λ ®N 5 g ^ Ϊ 4.86 ± 0.43 5.00 Earth 0.64 4_18 Soil 0.49 3.74 ± 0.42 2.36 ±0.19 TTCP/DCPA: CSH (weight ratio) 90:10 I 85:15 75:25 65:35 55:45 201217296 in Table 16 (by and 0.6M Summary of results shown in (NH4)2HP〇4 mixed TTCP/DCPA/CSH/KC1 (porogen) mixed powder prepared TTCP/DCPA/CSH composite porous block): (1) Under all test conditions, As the CSH content in the composite increases, the CS strength of the porous block decreases. (2) Porous block prepared by TTCP/DCPA/CSH/KC1 at TTCP/DCPA/CSH: KC 1:1 (water/oil) The CS value of the impregnation treatment is about 2-5 Mpa, and the CS value is about 0.4-0.9 Mpa at TTCP/DCPA/CSH:KC1=1:2. (3) The impregnation treatment significantly enhances the strength of the porous block. At TTCP/DCPA/CSH:KC1 = 1:1, the CS value of the (NH4)2HP〇4-impregnated porous block increased significantly to 4.8-8.9 MPa, and at TTCP/DCPA/CSH:KC1 = 1 At 2, the CS value is significantly increased to approximately 0.5-1.2 MPa. When TTCP/DCPA/CSH: KC1 = 1:1, the CS value of the porous block impregnated by Κ2ΗΡ〇4· is significantly increased to 4.8-8.8 MPa, and when TTCP/DCPA/CSH:KC1 = 1:2, The CS value was significantly increased to approximately 0.5-1 · 2 MPa. Example 11: Animal studies and determination of composite implant absorption ratio

Animal research was conducted at the Animal Center of the National Cheng Kung University School of Medicine in Tainan, Taiwan. Adult male (weight 2.8-3.5 kg), healthy male New Zealand white rabbits were used as experimental animals. The rabbit is individually packaged in a non-pound steel cage and the rabbit is free to access food and water. A minimum of 7 days of acclimation cycle is allowed between receipt of the animal and initiation of the study. The injection site was shaved and cleaned with 70% ethyl yeast and BetadineTM 44 201217296 (Povidone iodine 1%). All animals were operated under general anesthesia. Sodium pentobarbital (0.1 ml/100 g, Tokyo Kasei Kogyo, 曰本, Tokyo) was used as a general anesthetic agent' and lidocaine (Fujisawa Pharmaceutical CO., 曰本 'Tokyo) was used as a local anesthetic. In order to implant a cement paste in the medial malleolus of the femur, a longitudinal incision is made on the anterior surface of the femur. The inside of the rabbit knee was cut open to expose the femur. After exposing the femur, the periosteum was reflected and a 2 mm guide hole was drilled. The hole is gradually widened using a drill having an increased size until a final diameter of 5 mm is reached. Use a special 5 mm diameter drill burr and insert the ring at a depth of (7) claw to ensure proper length of the hole (1 〇 mm). Two calcium phosphate/calcium sulfate composite cement pastes (9 〇 wt% TTCP/DCPA: 10 wt% CSH and 55 wt% τ丁Cp/DcpA 45 wt% CSH) were implanted into the prepared bone cavity. After filling the paste, the subcutaneous tissue and skin are closed with layers of silk. In order to reduce the risk of infection during surgery, rabbits were treated with subcutaneous antibiotics at a dose of 40 mg/kg. The animals died after 12 weeks after surgery. Immediately after the animal dies, the femoral portion is removed and excess tissue is removed. The area of the residual implant is calculated using the sliced photo and image sub-system of the single lens reflex camera. The implant absorption ratio was determined by the following equation: implant absorption ratio = (cross-sectional area of the initial implant residual implant cross-sectional area) / cross-sectional area of the initial implant. Summary: The flats of the "90/10" and "55/45" samples are seen in the photos mentioned above. 45 201217296 Residual implant ratios were 8 1 · 1 % (absorption ratio 67.7% (absorption ratio: 32.3) %). This means that the 55/45 combined speed is about 70% faster than the 90/10 implant. 18.9%) and the implant 46

Claims (1)

201217296 VII. Patent application scope: 1. A bone cement formula containing a powder component and a solidified liquid component, wherein the ratio of liquid to powder is 〇2〇cc/g to 〇5〇cc/g, preferably Between 0.25 cc/g and 0.35 cc/g, wherein the powder component contains a source of sulfuric acid and a source of linonic acid, based on the total weight of the source of the sulfuric acid and the source of the male acid. The weight ratio is less than 6 5 %, and the solidified liquid component contains ammonium ions at a concentration of about 肘5 to 4 M, wherein 'the phosphoric acid source includes acid tetrasodium and discic acid di-s, wherein squaric acid The molar ratio of tetracalcium to dicalcium phosphate is from about 0.5 to about 2.5, preferably about 1.0, and the source of calcium sulfate is calcium sulfate hemihydrate, calcium sulfate dehydrate or anhydrous calcium sulfate 'and preferably calcium sulfate hemihydrate. Wherein the calcium component of the powder component is greater than 5%, more preferably from 1% to 55%, based on the total weight of the calcium sulfate source and the calcium phosphate source. 2. The formulation as claimed in claim 1, wherein the phosphoric acid #5 is an anhydrous tannin. 3. The formulation of claim 1, wherein the solidifying liquid component comprises ammonium ions having a concentration of from about 1.0 Torr to about 2.0 M. 4. The formulation of claim 3, wherein the solidifying liquid component is a solution of NH4H2P〇4, (NH4)2HP〇4, (NH4)3p〇4.3H20 or a mixture thereof. 47 201217296 5. The formulation of claim 4, wherein the solidifying liquid component is an aqueous solution of (NH4)2HP〇4. 6. The formulation of claim 2, wherein the calcium phosphate source consists of tetracalcium phosphate and anhydrous dicalcium phosphate. 7. The formulation of claim 1, wherein the formulation further comprises a pore former, and the pore former is dissolved when the hardened bone cement composite prepared from the formulation is impregnated into the solution _ In this solution. 8. A method of preparing a hardened bone cement composite, the method comprising: forming a bone cement paste by mixing a powder component of a bone cement formulation described in the scope of claim 2 with a solidified liquid component; Forming the paste; and removing the mold to form a block of hardened bone cement composite. 9. The method of claim 8, wherein the method further comprises: adding the paste in the mold to remove a portion of the liquid from the paste before the paste is cured; Decreasing the ratio of the liquid to the powder of the poly-paste, so that the pressure applied to the paste in the mold is about 1 λ &gt; Γτι MPa to 500 MPa, preferably 100 MPa to 500 MPa 〇10, such as The method of claim 8 wherein the method further comprises impregnating the block with a dipping liquid for a period of time such that the block is not compared to the block not subjected to the impregnation treatment. The compressive strength of the impregnated block obtained by the removal of the impregnation liquid is increased. 11. The method of claim 10, wherein the impregnation liquid is a phosphate-containing solution, wherein the concentration of the phosphate is from about 1 M to about 6 Torr, preferably from about 1 Torr to about 3 The method of claim 8, wherein the powder component of the bone cement formulation contains a pore former, or a pore former is added during the mixing, or in the mold The pore former is mixed with the paste prior to paste formation, and the method further comprises impregnating the block of the hardened bone cement composite in an immersion liquid to dissolve the pore former in the immersion liquid, A hole is formed in the block to form a porous block, and the porosity of the porous block is preferably from 50 to 90% by volume. The method according to claim 12, wherein the pore forming agent is selected from the group consisting of Lien, Ken, Nacn, MgCl2, Caci2, NaI〇3, KI, Na3P04, K3P04, Na2C03, amino acid - sodium salt, amino acid, salt, glucose, polysaccharide, fatty acid-sodium salt, fatty acid - bell salt, tartaric acid moxibustion, potassium carbonate, potassium gluconate, potassium sodium tartrate, potassium sulfate, sodium sulfate, lactate and nectar In the group consisting of alcohols. 14. The method of claim 12, wherein the 49 201217296 immersion liquid is a phosphate-containing solution or a water solution of the phosphate having a concentration of about 0.1 M to about 6 M. It is preferably from about 1 M to about 3 M. 15. The method of claim 12, wherein the method further comprises impregnating the porous block with a dipping liquid for a period of time such that compared to the porous block not subjected to the impregnation treatment The compressive strength of the impregnated porous block which is desired to be removed from the impregnation solution is improved. The method of claim 15, wherein the impregnating liquid is a phosphate-containing solution, wherein the phosphate concentration is from about 1 M to about 6 M, preferably from about 1 M to about 3 M. 17. The method of claim 8, wherein the method further comprises breaking the block into pellets. The method of claim iq, wherein the method further comprises breaking the porous mass into the porous mass. , 50 201217296 ' IV. Designated representative map: (1) The representative representative of the case is: ( ). (2) A brief description of the symbol of the representative figure: [None] 5. If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention: [None]