Calcium Phosphate Compositions and Process for Obtaining These Compositions from Grits Residue

Abstract

This invention patent describes a process for obtaining pure and biphasic nanostructured calcium phosphate compositions, particularly compositions of β-calcium pyrophosphate (β-CPP) and biphasic calcium phosphates [-CPP:-TCP and -CPP:Na2(HPO4)], from grits waste from the pulp and paper industry, using it as a precursor of calcium carbonate. The nanostructured calcium phosphate compositions derived from grits waste, the subject of this patent, are intended for applications in the biomedical field, with particular interest in bone tissue replacement and regeneration.

Description

"Calcium Phosphate Compositions and Process for Obtaining These Compositions from Grits Waste" Technical mastery of the invention [1] . The present invention patent consists of the process for obtaining pure and biphasic nanostructured calcium phosphate compositions, particularly calcium β-pyrophosphate (β-CPP) and biphasic calcium phosphate compositions [e-CPP:e-TCP and e-CPP:Na2(HPO4)], from grits residue from the pulp and paper industry, using it as a calcium carbonate precursor. The nanostructured calcium phosphate compositions derived from grits residue, the subject of this patent, are intended for applications in the biomedical field, with particular interest in bone tissue replacement and regeneration. Background of the invention [2] Calcium phosphate constitutes a class of biomaterial with high added value used in biomedical applications, mainly for bone grafts and implants. Calcium phosphates are attractive for biomedical use because they exhibit suitable properties in terms of biocompatibility, osteoconduction, and osteointegration. In addition, calcium phosphates exhibit chemical and mineral similarity to those of bones and tissues. It should be noted that calcium phosphates are used in biomedical applications in the form of cements, pastes, coatings, gels, and scaffolds. [3] . Calcium phosphates are classified in terms of their Ca / P molar ratio, which is in the range between 0.5 and 2.0. Among all synthetic calcium phosphates, hydroxyapatite - HAp (Ca10(PO4)6(OH)2) with a Ca / P value of 1.67 is recognized as the most important, being the most used in biomedical applications, since hydroxyapatite is the main component present in the mineral phase of bones. Petition 870200015660, dated 03 / 02 / 2020, page 7 / 22 2 / 10 [4] . On the other hand, the biomedical use of hydroxyapatite is limited due to its low reabsorption rate in vivo. This situation has led to the search for new pure or biphasic calcium phosphate compositions such as, for example, pure calcium β-pyrophosphate (β-CPP) and biphasic calcium phosphates. [5] . According to documents [1] and [2], biphasic calcium phosphates consist of the combination of two individual calcium phosphate phases. Biphasic calcium phosphate is usually described in abbreviated form as BCP (biphasic calcium phosphate). The main BCPs are HAp:e-TCP (hydroxyapatite:3-tricalcium phosphate), HAp:a-TCP (hydroxyapatite:a-tricalcium phosphate) and e-TCP:a-TCP (β-tricalcium phosphate:α-tricalcium phosphate), with the HAp:e-TCP composition being particularly noteworthy. BCPs are very attractive in biomedical applications because they exhibit improved bioactivity and biodegradability. [6] . The document [4], “SV Dorozhkin, Multiphasic calcium orthophosphate (CaPO4) bioceramics and their biomedical applications, Ceramics International, Vol. 42, 2016”, describes the most commonly used methods for the synthesis of the main BCPs (HAp:e-TCP, HAp:a-TCP ee—TCP:a—TCP), including methods such as sintering mixtures of different calcium phosphate powders, solid-state reactions, precipitation in aqueous solution, sol-gel process and hydrothermal method. [7] . Document [5] “EP 2 075 231 A1” refers to a European patent application filed on 28 / 12 / 2007 and published on 01 / 07 / 2009 in the name of the University of Vigo (Spain); Title: Biphasic calcium phosphate and method for obtaining the same from fish bones. This invention describes the process for obtaining biphasic calcium phosphate, specifically BCP type HAp:e-TCP characterized by the presence of 5 to 40 % by weight of β-TCP. Obtaining this BCP involves a controlled calcination process of fish bones as a precursor source using a calcination temperature between 600 °C and 1200 °C, with a heating rate of 18-22 °C / min. Petition 870200015660, dated 03 / 02 / 2020, page 8 / 22 3 / 10 [8] . The document [6], “Farzadi et al., Synthesis and characterization of hydroxyapatite / e-tricalcium phosphate nanocomposites using microwave irradiation, Ceramics International, Vol. 37, No. 1, 2011”, refers to obtaining HAp:e-TCP type BCP using a microwave-assisted synthesis method. The document indicates that microwave irradiation tends to increase the amount of the HAp phase in the synthesized biphasic calcium phosphate material. [9] . Document [7] “WO 2013 / 057720 A2” refers to a patent application filed on 19 / 12 / 2012 and published on 23 / 04 / 2013 in the name of Universidade Católica Portuguesa (UCP), Wedotech - Companhia de Ideias e Tecnologias LDA and Pascoal & Filhos SA; Title: Compositions and method for obtaining apatite-based compositions from natural sources, related materials and their uses. This invention describes obtaining hydroxyapatite and derivatives using fish bones (in particular cod spines) as a precursor source subjected to a controlled calcination process at temperatures between 600 °C and 1300 °C and a heating rate of 5°C / min for 1 h. Among the various calcium phosphate compositions obtained, there is one related to BCP of the HAp:FC type (hydroxyapatite:calcium phosphate), with a composition of HAp:FC (75:25) obtained between 900 °C and 1000 °C.

[10] . The document [8], “Arahira et al, Development and characterization of carbonate apatite / e-tricalcium phosphate biphasic cement, Materials Letters, Vol. 194, 2017”, describes the obtaining of carbonate apatite (CO3Ap):e-TCP type BCP using mixtures of α-TCP and β-TCP carbonated powders between 1 and 5 h with NaHCO3(1M) solution.

[11] . Parallel to this industrial demand, there is a demand for alternative and sustainable solutions for the final disposal of waste from the pulp industry in Brazil, which is ranked as the second largest producer of pulp in the world. According to document [3], in 2018, Brazilian pulp production was 21.085 million tons. Associated with this production of Petition 870200015660, dated 03 / 02 / 2020, page 9 / 22 4 / 10 of cellulose, it is also observed that large quantities of waste are obtained, especially grits.

[12] . Grits residue is obtained on a large scale via the Kraft process for cellulose extraction. This is a solid, inorganic and non-biodegradable residue, composed mainly of calcium carbonate in the form of calcite (CaCO3). This residue can be classified in terms of the Brazilian standardization of solid waste (ABNT NBR 10004) as Class IIA type solid waste - Non-Inert.

[13] . The final disposal of grits waste is a topic of high technical, economic and environmental interest. In terms of procedures for the final disposal of grits waste, the most commonly used practice is disposal in sanitary landfills. This procedure is costly for the industry, as well as being problematic for the environment. Therefore, the need to find an alternative and sustainable solution for the final disposal of grits waste becomes evident.

[14] . In order to contribute to solving the problem of the disposal of grits waste described above and, in parallel, to develop new biomaterials as alternatives to hydroxyapatite, the present invention patent proposes a process for obtaining nanostructured calcium phosphate powders, particularly pure and biphasic calcium phosphate compositions, from grits waste, using it as a precursor of calcium carbonate. Brief description of the figures

[15] . The figures described below relate to the structural and morphological characteristics of the calcium phosphate powders obtained, which facilitate the understanding of the present invention patent.

[16] . Figure 1 shows the X-ray diffraction (XRD) spectrum of the nanostructured e-CPP:3-TCP type BCP powder obtained from grits residue by the synthesis process of the invention with HNO3 (1.0 M). Petition 870200015660, dated 03 / 02 / 2020, page 10 / 22 5 / 10

[17] . Figure 2 shows the X-ray diffraction (XRD) spectrum of the e-CPP:Na2(HPO4) type BCP powder with traces of nanostructured β-TCP and HAp obtained from grits residue by the synthesis process of the invention with HNO3 (1.5 M).

[18] . Figure 3 shows the X-ray diffraction (XRD) spectrum of the e-CPP:e-TCP type BCP powder with traces of nanostructured Na2(HPO4) obtained from grits residue by the synthesis process of the invention with HNO3 (2.0M).

[19] . Figure 4 shows the X-ray diffraction (XRD) spectrum of βCPP powder with traces of nanostructured β-TCP obtained from grits residue by the synthesis process of the invention with HNO3 (2.5 M).

[20] . Figure 5 shows the X-ray diffraction (XRD) spectrum of pure nanostructured βCPP powder obtained from grits residue by the synthesis process of the invention with HNO3 (3.0M).

[21] . Figure 6 shows scanning electron microscopy micrograph of the typical morphology of nanostructured biphasic calcium phosphate powder obtained from grits residue by the synthesis process of the invention with HNO3 (2.0 M). Detailed description of the patent.

[22] . The present invention patent consists of nanostructured calcium phosphate compositions, pure and biphasic β-CPP, and a process for obtaining these compositions from grits residue as a calcium carbonate precursor. Specifically, the present invention makes it possible to obtain nanostructured calcium phosphate powders from grits residue using a wet precipitation method at different concentrations of HNO3.

[23] . The process of obtaining calcium phosphate powders consists of several steps, as described below. Step 1 - Processing of grits waste

[24] . In this step, the grits residue collected from the pulp industry is subjected to drying in an oven at 110 °C for 24 h, comminuted to dryness and passed through a 150 mesh sieve (< 106 μm ASTM). Mineralogical analysis by Petition 870200015660, dated 03 / 02 / 2020, page 11 / 22 6 / 10 X-ray diffraction indicated that the grits residue is primarily composed of calcium carbonate in the form of calcite (CaCO3). Chemically, this solid residue is primarily composed of calcium oxide (CaO) with approximately 96.51% by mass. Step 2 - Synthesis of calcium phosphate powders

[25] . In this step, the grits residue (composed mainly of CaCO3) was completely dissolved in an HNO3 solution (digestion solution) with different molar concentrations (1.0 M, 1.5 M, 2.0 M, 2.5 M and 3.0 M) and constant stirring for 2 h. The dissolution process resulted in the formation of several Ca(NO3)2 solutions derived from the molar concentrations of each digestion solution (1.0 M, 1.5 M, 2.0 M, 2.5 M and 3.0 M). The compound Na2HPO4 (PA grade 99%) was slowly added to the Ca(NO3)2 solutions, each mixture being vigorously stirred for 2 h at a temperature of 50 °C. This procedure resulted in the precipitation of a white substance for each solution. Step 3 - Filtering, washing and drying the substance.

[26] . This step consists of filtering the white substances (precipitates) obtained after the synthesis process using a funnel with filter paper assisted by primary vacuum. The precipitates were collected and washed with distilled water in order to eliminate any reaction impurities. Finally, the precipitates in the form of a white mass were dried in an oven at 110 °C for 24 h. Step 4 - Calcination of the precipitates

[27] . The filtered and dried white precipitates from the previous step were subjected to a calcination process using a muffle furnace at a temperature of 900 °C for 2h, a heating rate of 10 °C / min and an oxidizing atmosphere. Petition 870200015660, dated 03 / 02 / 2020, page 12 / 22 7 / 10 The products resulting from calcination are calcium phosphate powders. Step 5 - Analysis of calcined products

[28] . The calcined products were subjected to X-ray diffraction (XRD) analysis with a conventional Rigaku Ultima IV diffractometer using Cu-Kα radiation, to identify the crystalline phases present in all synthesized calcium phosphate powders.

[29] . The compositions of calcium phosphate powders obtained at different HNO3 concentrations in terms of β-CPP, β-TCP, HAp and Na2(HPO4) phases were determined by the Rietveld refinement method.

[30] . The average crystallite size (D) of the synthesized calcium phosphates was determined using Scheme's equation given by D = 0.9 λ / B cosθ, where λ is the wavelength of Cu-Kα radiation (λ = 0.15406 nm), B is the width at half height of the 100% intensity peak of calcium phosphate and θ is the diffraction angle.

[31] . The morphology of the calcium phosphate powder particles obtained was observed with a Shimadzu SSX-550 scanning electron microscope, voltage of 15 kV, after metallization with a thin conductive layer. Nanostructured biphasic calcium phosphate powders

[32] . In the context of the present invention, nanostructured calcium phosphate powders, in pure and biphasic β-CPP compositions, were obtained using grits residue as an alternative precursor to calcium carbonate, as described in detail above.

[33] . The calcium phosphate compositions synthesized from the grits residue showed variations depending on the HNO3 concentration (Figures 1-5). Thus, the following calcium phosphate powders were synthesized: i) HNO3 concentration (1.0 M) - biphasic calcium phosphate of the type e—CPP^-TCP (Figure 1); ii) HNO3 concentration (1.5 M) - biphasic calcium phosphate of the type Petition 870200015660, dated 03 / 02 / 2020, page 13 / 22 8 / 10 β-CPP:Na2(HPO4) with traces of β-TCP and HAp (Figure 2); iii) HNO3 concentration (2.0 M) - biphasic calcium phosphate of the e-CPP:e-TCP type with traces of Na2(HPO4) (Figure 3); iv) HNO3 concentration (2.5 M) - calcium phosphate of the β-CPP type with traces of β-TCP (Figure 4); and v) HNO3 concentration (3.0 M) - pure calcium phosphate of the β-CPP type (Figure 5).

[34] . Table 1 presents the quantitative phase compositions of the synthesized calcium phosphate powders at different HNO3 concentrations determined by the Rietveld refinement method. This table also presents the average crystallite size values ​​of the synthesized calcium phosphate powders, determined by Scherrer's equation, which were established in the range between 49.38 and 60.66 nm. These values ​​characterize the nanostructured nature of the synthesized calcium phosphate powders using grits residue. Table 1. Compositions and average crystallite size of calcium phosphate powders synthesized using grits residue. Concentration of HNO3 Composition of calcium phosphates (%) Average crystallite size (nm) β-CPP β-TCP Na2(HPO4) HAp 1.0 M 72.8 27.2 - - 56.74 1.5 M 87.7 0.9 11.2 0.3 56.86 2.0 M 83.4 15.2 1.3 - 59.57 2.5 M 99.3 0.7 - - 60.66 3.0 M 100.0 - - - 49.38

[35] . Morphological analysis using scanning electron microscopy (Figure 6) indicated that the synthesized calcium phosphate powders are essentially composed of particles with spherical or rounded morphology, but are highly agglomerated due to the calcination step at a temperature of 900 °C / 2h. Petition 870200015660, dated 03 / 02 / 2020, page 14 / 22 9 / 10

[36] Based on the qualitative identification of phases by X-ray diffraction, quantitative phase analysis by the Rietveld refinement method, average crystallite size determined by Scherrer's equation and morphological analysis by scanning electron microscopy, it is concluded that grits residue, produced in the pulp industry, constitutes an alternative source of renewable and low-cost calcium carbonate. Therefore, grits residue is suitable for use in the processing of nanostructured calcium phosphate powders to obtain compositions of pure calcium β-pyrophosphate (β-CPP) and biphasic calcium phosphates (e-CPP:e-TCP and e-CPP:Na2(HPO4)) with potential application in the biomedical field. References [1] SV Dorozhkin, Bioceramics of calcium orthophosphates, Biomaterials, Vol. 31, No. 7, p. 1465 - 1485, 2010. [2] M. Ebrahimi, M. G. Botelho, S.V. Dorozhkin, Biphasic calcium phosphates bioceramics (HA / TCP): Concept, physicochemical properties and the impact of standardization of study protocols in biomaterials research, Materials Science Engineering C, Vol. 71, p. 1293 - 1312, 2017. [3] IBÁ, Cenários IBÁ: Estatísticas da Indústria Brasileira de Árvores: 2° Trimestre de 2019, Brasília, Boletim 58, p. 1-7, 2019. [4] S.V. Dorozhkin, Multiphasic calcium orthophosphate (CaPO4) bioceramics and their biomedical applications, Ceramics International, Vol. 42, No. 6, p. 6529-6554, 2016. [5] M.B. Larosi, J.M.P. Saracho, R.C. Pineiro, F.L. Rodriguez, B.M.L. Fong, Biphasic calcium phosphate and method for obtaining same from fish bones, Patente EP 2 075 231 A1, 2009. [6] A. Farzadi, M. Solati-Hashjin, F. Bakhshi, A. Arminian, Synthesis and characterization of hydroxyapatite / e-tricalcium phosphate nanocomposites using microwave irradiation, Ceramics International, Vol. 37, No. 1, p. 65-71, 2011. Petition 870200015660, dated 03 / 02 / 2020, p. 15 / 22 10 / 10 [7] MME Pintado, P. Castro, C. Piccirillo, S. Moura, SIA Pereira, RMF Jorge, MIFOBC Guimarães, JG Vieira, PAM Silva, Compositions and method of obtaining apatite-based compositions from natural sources, related materials and their uses, Patent WO 2013 / 057720 A2, 2013. [8] T. Arahira, M. Maruta, S. Matsuya, Development and characterization of apatite phosphate / e-tricalcium biphasic cement, Materials Letters, Vol. 194, p. 205-208, 2017.

Claims

CLAIMS 1. Calcium phosphate compositions characterized by nanostructured calcium phosphate powders, in β-calcium pyrophosphate compositions of the βCPP type and biphasic calcium phosphates of the e—CPP:e—TCP and e—CPP:Na2(HPO4) types.

2. Calcium phosphate compositions, according to Claim 1, characterized by employing grits residue, composed mainly of calcite (CaCO3), as a total substitute for conventional carbonaceous raw material.

3. Process for obtaining calcium phosphate compositions characterized by using different concentrations of HNO3 (1.0 M, 1.5 M, 2.0 M, 2.5 M and 3.0 M) to dissolve grits residue and produce different Ca(NO3)2 solutions.

4. Process for obtaining calcium phosphate compositions, according to Claim 3, characterized by slowly adding Na2HPO4 to solutions of HNO3 and grits residue, in order to obtain crude calcium phosphate precipitates.

5. Process for obtaining calcium phosphate compositions, according to Claims 3 and 4, characterized by subjecting crude calcium phosphate precipitates to washing with distilled water and drying in an oven at 110 °C for 24 h.

6. Process for obtaining calcium phosphate compositions, according to Claims 3 to 5, characterized by subjecting crude calcium phosphate precipitates to calcination, using a muffle furnace at a temperature of 900 °C for 2 hours, a heating rate of 10 °C / min and an oxidizing atmosphere.

7. Process for obtaining calcium phosphate compositions, according to Claims 3 to 6, characterized in that the use of different concentrations of HNO3 made it possible to obtain the following crystalline phases: i) HNO3 (1.0 M): biphasic calcium phosphate of the e-CPP:p-TCP type; ii) HNO3 (1.5 M): biphasic calcium phosphate of the e-CPP:Na2(HPO4) type with traces of β-TCP and hydroxyapatite; iii) HNO3 (2.0 M): biphasic calcium phosphate of the βCPP:e-TCP type with traces of Na2(HPO4); iv) HNO3 (2.5 M): calcium phosphate of the β-CPP type with traces of β-TCP; ev) HNO3 (3.0 M): calcium phosphate of the βCPP type.

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