• 专利附录
  • 专利说明
  • 权利要求
  • 类似技术
  • 同族专利
  • 引用文献
  • 法律状态
  • 优先权
    • 专利摘要:
    New formulation for obtaining porous (unpolished) materials with biocompatible and bioactive surface for their potential application as substitutes for a bone graft in those clinical situations where biological stimuli are required to achieve bone regeneration. The material comprises α, calcium sulfate hemihydrate (α -SCH), β -tricalcium phosphate (β -TCP) & dicalcium silicate (γ -C 2 S).
    公开号:ES2697691A1
    申请号:ES201730965
    申请日:2017-07-24
    公开日:2019-01-25
    发明作者:Olmo Luis Meseguer；Ros Rubén Rabadan；Tarraga Patricia Ros
    申请人:Fundacion Universitaria San Antonio；
    IPC主号:
    专利说明:

    [0001]
    [0002]
    [0003]
    [0004] The object of the present invention is a new formulation for obtaining porous (unpolished) surfaces with a biocompatible and bioactive surface for their potential application as substitutes for a bone graft in those clinical situations where biological stimuli are required to achieve regeneration that is.
    [0005]
    [0006] The present invention falls within the technical field of manufacturing biocompatible and bioactive materials for bone reconstructive surgery in general, in the medical fields of orthopedic surgery and orthopedics, oral surgery, maxillofacial surgery and neurosurgery.
    [0007]
    [0008] State of the prior art
    [0009]
    [0010] To this day, the standard of bone replacement remains the autologous bone graft. The technique of using the autograft consists of taking bone tissue from another area of the skeleton (donor site) of the same patient, either from the same bone or from another. The main drawbacks of autografts are those arising from the search and sacrifice of the donor site, which causes a comorbidity of up to 25% in the patient and limited availability when large quantities of bone are needed for grafting [1]. Due to all these drawbacks of autografts, over the last decades, different alternatives to the use of these have been studied, such as natural or synthetic "bone substitutes", among which include calcium phosphate ceramics (mono and biphasic), bioglasses, calcium sulphate (a-SCH) or Paris plaster, composites, polymers, etc. Of these, bioceramics are the most widely used and, in particular, the so-called third generation ones, these are the matrices of biologically active molecules, which besides being bioactive and reabsorbable, stimulate the regeneration of living tissues through a specific cellular response. They are preferred to be used as matrices in tissue engineering.
    [0011]
    [0012] The requirements of an ideal bone substitute are: biocompatibility, biodegradability, mechanical efficacy for the specific application, bioconductivity, bioactivity, ease of sterilization and storage and reasonable cost-effectiveness ratio. The comparison with the spongy autograft, shows that, although the conductivity of the structure is common, the osteogenic and osteoinductive capacities are absent. Tissue engineering attempts, adding cells and signal proteins to equip these materials with the standard qualities of the grafts.
    [0013]
    [0014] As a substitute for bone tissue, one of the first materials investigated was Paris plaster (CaSO4-1 / 2H2O) [a-SCH]. This is obtained by calcination process of the natural gipsite at a temperature of 110-130 ° C with which 75% of the water is lost. It was used for the first time in 1892, by Dreesman, to fill bone defects created by tuberculous osteomyelitis. Its process of resorption causes a controlled increase in porosity while forming new bone. Its use is limited given its rapid reabsorption (4-8 weeks) and its poor structural stability that makes it prone to fractures when loading starts early.
    [0015]
    [0016] The raw material for its manufacture is cheap and abundant. It has been used both for filling bone defects and as a vehicle for controlled release of drugs and growth factors [2].
    [0017]
    [0018] Normally, local dissolution of the gypsum causes an increase in the release of calcium ions [Ca] and acidification of the medium that can affect the function of bone cells (osteoblasts) and therefore a certain degree of bone demineralization in situ. Although on some occasion a mitogenic effect on undifferentiated cells has also been described. Contrarily, this fact can inhibit osteoclastic activity, causing an imbalance in the bone formation / resorption balance that takes place in the process of bone remodeling. With our material, an inverse process is observed, that is, it causes the alkalinization of the medium, which contrasts with what happens with the dissolution of the isolated gypsum.
    [0019]
    [0020] The studies referring to preclinical and clinical applications have been focused on tests in animals in the field of dentistry to treat periodontal defects. For this purpose, various compositions have been tried:
    [0021]
    [0022] - Demineralized and lyophilized allogenic bone (a-SCH) [3]
    [0023] - Demineralized bone matrix (DBM) (a-SCH) [4,5]
    [0024] - Autologous bone (a-SCH) [6]
    [0025] - Chiotosa (a-SCH) BMP [7]
    [0026] - Phosphate-Ca silicate (a-SCH) [8]
    [0027] - Hydroxyapatite (a-SCH) [9]
    [0028] - PRP (a-SCH) [10]
    [0029] - Acrylic cements (PMMA) (a-SCH) [11]
    [0030] - Antineoplastics (metrotexate) (a-SCH) [12].
    [0031] - Allografts (a-SCH) [13,14]
    [0032] - Bioglass (a-SCH) [15]
    [0033] - Carboxymethyl cellulose (a-SCH) [16]
    [0034] - Hyaluronic Ac (a-SCH) [17]
    [0035] - Polylactic Ac (a-SCH) [5]
    [0036] - Ac. Polyacrylic (a-SCH) [18]
    [0037]
    [0038] Unfortunately, the results observed with the use of the different materials or compositions described are not comparable due to the heterogeneity of the designs of the studies carried out (type of animal, duration of study, cell lines used, place of implantation, etc.).
    [0039]
    [0040] The association of a-SCH with other inorganic compounds in an effort to improve handling / handling and physical properties, have not given all the expected optimal results [19], although it is true in some situations its bioactivity is improved. This bioactivity expressed as a reabsorption / deposition combination of a granular neolayer on the surface of the material and of composition close to the hydroxyapatite is similar to that observed with the bioglasses.
    [0041]
    [0042] The addition of TCP to treat critical bone defects in dogs improved the repair of the defect by comparing it with the unfilled control [20].
    [0043]
    [0044] Gypsum possesses many of the desired qualities of an ideal regenerative material, such as: (a) complete reabsorption at a short period of time (1 mm per week), (b) excellent biocompatibility, (c) abundant supply of Ca ions. , (d) relatively cheap, easy to handle and mold before setting, (e) excellent properties as a carrier for different types of molecules (various antibiotics, growth factors, antineoplastics, etc.). Although it also shows some disadvantages: rapid resorption and contact with biological fluids slows the setting which could question its permanence at the implantation site.
    [0045] Although part of the trials refer to the usefulness of gypsum in bone regeneration, there are some negative reports in animal studies [15]. But a problem that makes comparisons difficult lies in the heterogeneous nature of gypsum studies. Despite this, a-SCH is nowadays used for bone cavity filling in reconstructive surgery both orally and in other surgical disciplines (orthopedics and traumatology, maxillofacial surgery, etc.) [21] [22].
    [0046]
    [0047] Another aspect of interest is the high temperature reached by certain formulations, such as polymethylmethacrylate (PMMA) cements during the polymerization process (setting) within a few minutes of mixing. This material conserves the same temperature equal to the ambient temperature (22 ° C) during the whole setting process, reason for which we discard the negative effect that the exothermic reactions have on the adhesion and cellular viability and ultimately on the adjacent tissues.
    [0048]
    [0049] In preclinical studies in vivo that are being carried out in animal model (NZ rabbit), the effects of the new material are evaluated in terms of its potential osteogenic capacity, osteoinductive, osseointegration, degree of reabsorption, etc. In the present document, cytotoxicity, cell viability or proliferation, protein adsorption, bioactivity, ionic release, setting time and temperature recorded or detached during setting of the material object of the present invention have been evaluated.
    [0050]
    [0051] Bibliography
    [0052] [1] Gazdag A, Lane J, Glaser D, Forters R. J Am Acad Orthop Surg. 1995; 3: 1-8.
    [0053] [2] Thomas MV, Pileo D. J Biomed Mater Res Part B: Biomater appl 2009, 88B: 597-610.
    [0054] [3] Kim CK, Kim HY, Chai JK, et al. J Periodontol 1998, 69: 982-988.
    [0055] [4] Kim CK, Chai JK, Cho KS, et al. J Periodontol 1998, 69: 13171324.
    [0056] [5] Rosen PS, Reinols MA. J. Periodotol 1999, 70: 554-561.
    [0057] [6] Macneill SR, Cobb CM, Rapley JW, et al. J Clin Periodontol 1999, 26: 239-245.
    [0058] [7] Cui X, Zhang B, Wang Y, Gao Y. J Craneofac Surg 2008, 19: 459-465.
    [0059] [8] Hing KA, Wilson LF, Buckland T. Spine 2007, 7: 475-490.
    [0060] [9] Frenkel SR, Simon J, Alexander H, et al. J Biomed Mater Res 2002, 63: 706-713.
    [0061] [10] Intini GE. Tissue Eng 2002, 104: 384-386.
    [0062] [11] Tuzuner T, Uygur I, Sencan I, et al. J Orthop Sci 2007, 12: 170-177.
    [0063] [12] Vechasilp j. J Orthop Res 2007,15: 56-61.
    [0064] [13] Wright HB. University of Kentucky College of Dentistry, 2004, 62p.
    [0065] [14] Sottonanti Calciun sulphate. Compedium 1992, 13: 226-228
    [0066] [15] Melo LG, Nagata MJ, Bosco AF, et al. Clin Oral Implants Res 2005, 16: 683-691.
    [0067] [16] Vance GS, Greewell H, Miller RL et al. J Oral Maxillofac Implants 2004, 19: 491-497.
    [0068] [17] Lewis KN, Thomas MV, Puleo DA, et al. J Mater Sci Mater Med 2006, 17: 531-537.
    [0069] [18] Neira-Carrillo, Yazdani-Pedram M, Retuert J, et al. J Colloid Interface Sci 2005; 286: 134-141.
    [0070] [19] Huan Z, Chang J. Acta Biomater 2007, 3: 952-960.
    [0071] [20] Urban RM, Turner TM, Hall DJ, et al. Clin Orthop Relat Res 2007, 459: 110-117.
    [0072] [21] Kelly CM, Wilkins RM. Orthopaedics 2004, 27: 131-135
    [0073] [22] Kelly CM, Wilkins RM, Gitelis S, Harjten C, et al. Clin Orthop Relat Res 2001, 42-50
    [0074]
    [0075] Explanation of the invention
    [0076]
    [0077] The present invention relates to the obtaining of composite pieces of a-SCH p-TCP and C 2 S that act as a scaffold to promote and direct bone growth at the site of its implantation, facilitating the process of regeneration of bone and bone tissues. , as a consequence, the repair of bone defects. Likewise, it is intended to improve certain properties such as: bioactivity, setting time, cell adhesion and handling, comparing it with the a-SCH that has been used, in the present invention, as a control material due to the fact that it is a resorbable material widely used for decades, both experimentally and in clinical practice.
    [0078]
    [0079] The invention consists of obtaining a material with the described characteristics as a result of the mixture of three components a-sulfate calcium hemihydrate (α-SCH) [CaSO 4 -1/2 H 2 O], p-tricalcium phosphate (p-1) TCP) [Ca 3 (PO 4 ) 2 ] and dicalcium silicate (and C 2 S) [ 2 CaO.SiO 2 ] in a certain proportion. For the in vitro tests, compact pieces of 7.5 mm in diameter and 2.65 ± 0.2 mm in height have been obtained.
    [0080]
    [0081] In preclinical in vitro tests , the material has been shown to be biocompatible, no signs of cytotoxicity being observed, likewise, capable of absorbing proteins on its surface and something inside it, and being highly bioactive, as observed at 24 hours immersion in simulated human fluid (SBF). These facts facilitate cell adhesion on the surface of the material by recognizing the integrins of the cell wall the glycine, arginine and aspartic sequence (GRD) of the adhered proteins. The reaction of the two phases liquid / powder corresponding to the three components does not cause exothermic reaction that could cause cellular damage or alteration of the protein layer. Finally, the time of setting or solidification is not higher than that observed with the a -SCH. Therefore, we consider that this new three-phase and bioactive compound, can be considered a suitable material for its application in the filling of bone defects of any etiology, in those fields of bone reconstructive surgery, such as orthopedic surgery and traumatology, oral surgery and maxillofacial and neurosurgery.
    [0082]
    [0083] Throughout the description and claims the word "comprises" and its variants are not intended to exclude other technical characteristics, additives, components or steps. For those skilled in the art, other objects, advantages and characteristics of the invention will emerge partly from the description and partly from the practice of the invention. The following examples and drawings are provided by way of illustration, and are not intended to restrict the present invention. In addition, the present invention covers all possible combinations of particular and preferred embodiments indicated herein.
    [0084]
    [0085] BRIEF DESCRIPTION OF THE DRAWINGS
    [0086]
    [0087] Next, a series of drawings that help to better understand the invention and that are expressly related to an embodiment of said invention that is presented as a non-limiting example thereof, is briefly described.
    [0088]
    [0089] FIG.1 shows the ultrastructural aspect of the components of the mixture of the biomaterial object of the invention, as well as their respective analysis by means of X-ray diffraction (EDX).
    [0090]
    [0091] FIG.2 shows in a schematic way the steps followed to obtain the appropriate mixture, and prior to adding liquid phase (A) to obtain a material with characteristics and consistency similar to "toothpaste". Appearance of the pieces forging in their mold (B) and finally, the pieces of the disc-shaped material obtained (C).
    [0092]
    [0093] FIG. 3 schematically shows the setting time and thermal behavior of the mixture of the material object of the invention, including: the perceptible mark on the surface of the material (Fig. 3-A); Fig. 3-B. Comparative images of brands caused by the needle on the surface of the specimens, a-SCH in contact with bovine serum (upper row), a-SCH (central row) and material of the invention (lower row); Fig. 3-C. Temperature variations recorded during the setting process at room temperature
    [0094]
    [0095] FIG.4 shows the determination of the adsorption of proteins on the surface of the material by means of the Coomassie colorimetric test. (a) Blue coloration of the material impregnated with proteins on its surface (Coomassie test); (b) Quantification data of the absorbed proteins.
    [0096]
    [0097] FIG. 5 graphically shows the results of the ion release analysis (Ca, P, S, Si) and pH of the material object of the invention immersed in complete culture medium (DMEM) by ICP-OES ( Inductively coupled plasma-optical emission) spectrometry spectometer).
    [0098]
    [0099] FIG.6 shows various aspects of the characterization of the material carried out by: (FIG.6A) ultra structural appearance of the material by scanning electron microscopy (SEM) at different magnifications and table with results of the microanalysis; (FIG.6B) X-ray diffraction (EDX); and (FIG.6C) infrared by Fourier transform-Attenuated Total Reflectance (FTIR).
    [0100]
    [0101] FIG.7 In the bioactivity test performed, shows by SEM the appearance of the material surface, (a) Limit of the newly formed apatite layer on the surface of the material (arrow), (b) Thickness of the layer in a section perpendicular to the surface, (c) deposited crystallization nuclei, (d) detail of the previous image at higher magnification (bar 3 ^ m).
    [0102]
    [0103] FIG.8: (a) the results obtained in the cytotoxicity tests compared to Paris plaster using SEM and (b) cell proliferation test on the material by reducing the tetrazolium salt (MTT) to 1, 3, 5 , 7 days.
    [0104]
    [0105] Presentation of a detailed embodiment of the invention and example
    [0106]
    [0107] The present invention relates to a process for obtaining a biocompatible and bioactive three-phase material obtained by mixing a-SCH (main component) pTCP YC 2 S in the proportion or ratios 4: 1: 1 (66.6, 16.6 and 16.6 w%, respectively) for its potential use in the regeneration of bone tissue.
    [0108]
    [0109] Once the mixture of the solid phase (powders) was made, deionized water was added in the established liquid / powder ratio of 0.33 ml g-1. Next, the material acquires a pasty appearance similar to the " medium tooth" toothpaste , and is when it is poured on the mold and left to set-dry in an oven at 37 ° C for 24 hours. Finally, the samples were removed from the molds and stored in a sealed container in a dry oven environment. The new material obtained shows a discoid shape of 7.5 mm in diameter and 2.65 ± 0.2 mm in height and of average weight 216 ± 5 mg, of compact appearance that avoids the technical complications caused by dispersion of the material during its subsequent manipulation when they are carried performed in vitro studies and in vivo tests (intraosseous implantation). Due to the characteristics of the material and its behavior in vitro, it is expected that it is potentially reabsorbable in the medium term (4-6 months), so it would not require its subsequent removal from the place where it was implanted.
    [0110]
    [0111] Figure 1 shows ultra structural appearance of the components of the mixture (P-tricalcium phosphate (P-TCP) [Ca 3 (PO 4 ) 2 ], dicalcium silicate ( and -C 2 S) [2CaO.SiO2], and a-SCH ), as well as their respective microanalysis through EDX. Figure 2, on the other hand, schematically shows the steps followed to obtain the appropriate mixture, and prior to adding liquid phase (A) to obtain a material with characteristics and consistency similar to "toothpaste". Appearance of the pieces forging in their mold (B) and finally, the pieces of the disc-shaped material obtained (C).
    [0112]
    [0113] Figure 3 refers to the setting time and thermal behavior. A modified Gillmore technique was used [Kokubo T, Shigematsu M, Nagashima Y, Tashiro M, Nakamura T, Yamamuro T, et al. Bull. Inst. Chem. Res. Kyoto Univ., 60, 260, 1982] to obtain qualitative data. The tip of the indenter is 1 mm in diameter and concentrates a load of 50 grams. Defining as setting time, the time elapsed since the liquid / powder mixture is made and the paste obtained is deposited in the molds, until the needle does not leave an indentation or perceptible mark on the surface of the material. (Fig. 3-A) The test was performed on 5 samples (n = 5) of each material. The results have allowed to affirm that the setting time of the material object of the invention was twelve minutes, similar to that of the a-SCH. This time increased markedly when the deionized water was replaced by fetal bovine serum to simulate a biological environment in contact with organic fluids (Fig. 3B, upper row).
    [0114]
    [0115] To determine the possible temperature variations during the setting process, an infrared thermometer Flash III-Ther-L02 was used. The data collection was made to coincide with the time taken to determine the degree of setting of the material (Fig. 3-C).
    [0116]
    [0117] Figure 4 shows the determination of the adsorption of proteins on the surface of the material by means of the Coomassie colorimetric test. (a) Penetration level of the staining equivalent to protein absorption. (b) Quantitative test by elemental nitrogen analyzer LECO FP-528 and expressed by bar diagram. Tests carried out at 1h and 24 hours of immersion of the material in fetal bovine serum and kept in an incubator at 37 ° C during this period.
    [0118]
    [0119] Figure 5 graphically represents the results of the ion release analysis (Ca, P, S, Si) and pH of the material object of the invention immersed in complete culture medium (DMEM) by ICP-OES ( Inductively coupled plasma-optical emission) spectrometry spectometer). Determinations made at 1, 3, 6 hours and 1, 2, 3, 4 and 7 days. The most relevant changes, greater release of ions, are observed after 24 hours of immersion, which cause a slight alkalinization of the culture medium (pH 8.16-8.2).
    [0120]
    [0121] The pH values were measured using an electrode of a digital pH meter. Before carrying out any measurement, the pH meter was calibrated with a standard pH solution. The samples were placed in 15 ml Falcon tubes containing 10 ml of PBS buffer. The pH measurements of these solutions were carried out at room temperature at 1 and 24 hours of immersion.
    [0122]
    [0123] Table I, collects the data referring to the process of dilution of the material object of the invention comparing it with the material a-SCH. The test was carried out on six discs (n = 6) of each material. These were individually weighed before being deposited in their respective wells of a 24-well plate and held in place by a grid. They were immersed in MilliQ deionized water and in magnetic stirring continuously for 24 hours. Next, the supernatant was removed, dried in an oven at 60 ° C and, finally, individually weighed again.
    [0124]
    [0125] The results obtained are shown in the table below as the average of the recorded data expressed in grams.
    [0126]
    [0127]
    [0128]
    [0129] The analysis of these data reveals that, although part of equal weight in the powder phase, and using some kind of mold in the pulp phase after adding water, the weights after drying, on average, are lower in the material of the invention. In addition, sometimes, there is no direct relationship between the piece that weighs the most with the amount of material lost or diluted, that is, that at higher weight there is no higher rate of dilution. Finally, the material object of the invention presents a loss of 4.76% higher than a-SCH (0.009 g).
    [0130]
    [0131] Figure 6 shows various aspects of the characterization of the material carried out by: (FIG.6A) ultra structural appearance of the material by scanning electron microscopy (SEM) at different magnifications and table with results of the microanalysis; (FIG.6B) X-ray diffraction (EDX); and (FIG.6C) infrared by Fourier transform-Attenuated Total Reflectance (FTIR).
    [0132]
    [0133] In FIG. 6B the X-ray diffraction pattern of a-SCH and the invention is observed. The material object of the invention has, mainly, corresponding peaks with dehydrated gypsum and hemihydrated gypsum (sheets ASTM n ° 33-0311 and 41-0224 respectively). The rest of the phases are mainly overlapping with the gypsum, although the presence of the phases p-TCP and yC 2 S (sheets ASTM n ° 55-0898 and 87-1257 respectively) can be seen in the peaks that arise 27.8 20 and 32.5 - 32.6 20, and in the intensity increase of the peak located at 29.720, effect produced by the presence of yC 2 S.
    [0134]
    [0135] FIG. 6C shows the different spectra of the materials p-TCP, and C 2 S, gypsum and the material of the invention obtained by means of an IRTF-ATR (Infrared by Fourier Transform - Attenuated Total Reflectance) equipment. As we can see, in the spectrum obtained from the material of the invention the presence of both the plaster and the p-TCP and the yC 2 S can be seen. The plaster is the majority component, as would be expected, and the p-TCP and the and C 2 S appear in the range of 1200 to 800 cm-1.
    [0136]
    [0137] The ability of an apatite layer to form on the surface of the material when it comes in contact with the SBF is an in vitro procedure always used to determine the bioactivity of a biomaterial with a view to its application in bone repair. This test was carried out by immersing the material for 24 hours with SBF following the protocol of Kokubo et al. [Kokubo T, Shigematsu M, Nagashima Y, Tashiro M, Nakamura T, Yamamuro T, et al. Bull. Inst. Chem. Res. Kyoto Univ., 60, 260, 1982]. FIG.7 shows the appearance of the surface of the material, (a) Limit of the newly formed apatite layer on the surface of the material (arrow), (b) Thickness of the layer in a section perpendicular to the surface, (c) crystallization nuclei deposited and (d) detail of the previous image at higher magnification (Magnification bar 3 ^ m).
    [0138]
    [0139] Figure 8 shows the results obtained in the cytotoxicity tests compared with plaster of Paris by scanning electron microscopy and cell proliferation test by reducing the tetrazolium salt (MTT) to 1, 3, 5, 7 days. Multipotent undifferentiated cells of the cryopreserved bone marrow that were donated by the cellular therapy unit of Hospital UV Arrixaca were used. The test was carried out following the ISO-10993-5 standard, by direct and indirect tests using inserts and 24-well plates that allowed to keep the material without contact with the adult stem cells grown in the wells at a density of 5 x 103 cm-2 cells. The incubation was carried out under standard conditions of temperature, CO 2 and relative humidity. (A) Images representative of the adhesion of the adult mesenchymal stem cells (MSCs-A) on the surface of the material at 24 h of incubation. (B) Polygonal morphology with extensive cytoplasmic prolongations (filopodia) of the cells at 7 days in culture. (Bar 100 ^ m). (C) Results of the cell proliferation assay (MTT) comparing it with growth on gypsum at 1, 3 and 7 days in culture.
    [0140]
    [0141] Therefore, as has been indicated, the cytotoxicity tests carried out indicate that the material developed exhibits great potential for its application in bone reconstruction, without waiting for an adverse immune response that leads to cell damage. The material object of the invention shows a degree of bioactivity far superior to a-SCH as can be observed after remaining 24 hours in contact with the SBF. The ionic release by the material of the invention is maximum at 24 hours and does not cause significant changes, except for slight alkalization in the pH of the medium.
    [0142]
    [0143] The set time has been the same for both materials. A long setting time can cause a difficulty to maintain its structure at the time of its implantation in the bone defect to be repaired, indirectly leading to a loss of mechanical resistance, at least initially. No changes in temperature have been detected during the setting process, keeping or decreasing slightly with respect to the ambient temperature. The fact that an exothermic reaction is not triggered is considered favorable both for the adhesion of proteins and for cell adhesion. The presence or contact of the materials with biological fluids such as fetal calf serum (FCS) in substitution of deionized water considerably slows the setting time.
    [0144]
    [0145] This material was designed, developed and tested with the intention of increasing the degree of bioactivity and cell proliferation, without changing the setting time, maintaining the histocompatibility properties, comparing it with the a-SCH.
    权利要求:
    Claims (7)
    [1]
    1. A material for bone regeneration characterized by comprising calcium a-sulfate hemihydrate (a-SCH), p-tricalcium phosphate (P-TCP) and dicalcium silicate (YC 2 S).
    [2]
    2. The material of claim 1 wherein the ratio or ratio of the mixture of α-SCH, p-TCP and YC 2 S is 4: 1: 1.
    [3]
    3. A method for obtaining a bone regeneration material according to any of claims 1 or 2, characterized in that it comprises the steps of:
    to. Mix in solid phase a-SCH, p-TCP and YC 2 S;
    b. Add deionized water;
    c. Pour over a mold and set-dry in an oven at 37 ° C for 24 hours.
    [4]
    4. The method of claim 3 wherein the solid phase mixture of α-SCH, p-TCP and YC 2 S is carried out in a ratio of 4: 1: 1.
    [5]
    5. Use of the material defined in any of claims 1-2 or obtained according to the method of any of claims 3-4 in the preparation of a preparation for the regeneration of bone tissue.
    [6]
    6. Use of the material defined in any of claims 1-2 or obtained according to the method of any of claims 3-4 in the preparation of a preparation for bone reconstructive surgery.
    [7]
    7. Use of the material defined in any of claims 1-2 or obtained according to the method of any of claims 3-4 in the preparation of a preparation for the replacement of bone grafts.
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    同族专利:
    公开号 | 公开日
    ES2697691B2|2019-10-11|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US20060078590A1|2004-09-10|2006-04-13|Leif Hermansson|Resorbable ceramic compositions|
    US20060213395A1|2005-03-25|2006-09-28|Donghui Lu|Hydraulic cement compositions and methods of making and using the same|
    US20070098811A1|2005-10-31|2007-05-03|Donghui Lu|High strength biological cement composition and using the same|
    WO2008048182A1|2006-10-18|2008-04-24|Doxa Ab|Injectable resorbable ceramic compositions|
    JP2012087013A|2010-10-20|2012-05-10|Kyushu Univ|Hydraulic powder excellent in fluidity, and hydraulic composition|
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    ES201730965A|ES2697691B2|2017-07-24|2017-07-24|Procedure for obtaining a material for bone regeneration and material thus obtained|ES201730965A| ES2697691B2|2017-07-24|2017-07-24|Procedure for obtaining a material for bone regeneration and material thus obtained|
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