机械活化增强多孔磷酸钙骨水泥支架的研究

本研究采用球磨对磷酸钙骨水泥(CPC)起始粉末进行机械活化处理, 以期改善CPC力学性能, 并探讨了其影响机理。采用激光粒度仪、比表面积测量仪和X射线衍射仪(XRD)表征球磨后的CPC粉末(Ball milling CPC, BCPC)。利用发泡法制备多孔BCPC支架, 采用万能力学试验机、XRD和扫描电子显微镜(SEM)表征多孔BCPC支架。结果显示, 球磨后的BCPC粉末平均粒径减小, 比表面积增大, 表观密度、堆积密度及紧密密度减小。BCPC支架孔隙率为(77.98 ± 0.58)%, 抗压强度为(4.11 ± 0.46) MPa, 相比CPC支架的(64.23 ± 2.32)%和(1.99 ± 0.43) MPa有显著提高。SEM结果显示BCPC支架具有数微米和数百微米的两种孔隙结构。XRD结果表明机械活化作用降低了DCPD、α-TCP、CaCO₃和HA的晶粒尺寸和结晶度, 促使DCPD向DCPA转化, 促进了各相磷酸钙盐的水化和HA的沉积, 提高了BCPC支架的力学性能, 为增强CaP基多孔材料的力学性能和扩展其临床应用提供了新途径。     

骨碎补载入对磷酸钙骨水泥性能的影响及体外生物学评价

通过在湿法合成的二水磷酸氢钙膏体中加入中药骨碎补的提取物, 作为磷酸钙骨水泥(Calcium Phosphate Cement,CPC)原料之一, 分别制备0、5wt%、10wt%和15wt%的载骨碎补磷酸钙骨水泥. 采用Gilmore针、X射线衍射仪、红外光谱仪、万能材料试验机、扫描电子显微镜和紫外分光光度计研究载骨碎补CPC的理化性能和药物释放; 体外培养MC-3T3成骨细胞, 进行Alamar Blue和碱性磷酸酶检测, 研究载骨碎补CPC对成骨细胞增殖和分化的影响, 扫描电子显微镜观察细胞形貌. 结果表明: 随骨碎补浓度的增加, CPC凝结时间明显延长, 其抗压强度显著提高; 骨碎补促进初期CPC的水化, 却阻碍了α-磷酸三钙的转化, 且随骨碎补浓度增大作用愈明显, 骨碎补不影响CPC水化后的相成分; 含骨碎补CPC的微观形貌中出现片状和针状晶体, 结构较空白CPC更加致密; 药物释放分为突释和缓释两个阶段, 符合Higuchi基质扩散释放模型; 载骨碎补CPC对成骨细胞的作用呈剂量和时间依赖关系, 培养5d时浓度为5wt%和10wt%的CPC较明显地促进细胞增殖, 7d时载骨碎补CPC的细胞增殖较稳定, 细胞分化能力无显著性差异; 成骨细胞在载骨碎补CPC表面生长形态良好, 表明该材料具有较好的生物相容性.     

A Comparison of Trehalose Dihydrate and Mannitol as Stabilizing Agents for Dicalcium Phosphate Dihydrate Based Tablets

This study investigated the possible utility of trehalose dihydrate (TD) as a tablet stabilizing agent. Acetylsalicylic acid was used as the model hydrolyzable drug and dicalcium phosphate dihydrate (DCPD) as the base excipient, because it is well documented that ASA/DCPD tablets are unstable during storage at low temperature and high relative humidity; DCPD is usually combined with mannitol in order to improve tablet stability.

Tablets comprising DCPD, 10% ASA, and 0%, 10%, or 20% w/w of TD were prepared by direct compression and stored at 35°C and 82.9% relative humidity for 6 months. Additionally, control tablets with DCPD and ASA, only, or with DCPD, ASA and 20% mannitol, were also evaluated. At predetermined time intervals, formulations were tested for drug content, mechanical, microstructural, and drug dissolution properties. Additionally, thermal analyses and ASA solution stability studies were carried out. Results reveal that both TD and mannitol significantly reduce degradation of ASA included in DCPD-based tablets, but neither effectively protects against the marked decline in tablet mechanical properties on aging. The ASA stabilization effects of TD and mannitol were also observed in solution, indicating an interaction between these sugars and ASA.     

纳米晶体纤维素增强磷酸钙骨水泥的研究

本研究探索具有良好力学性能的纳米晶体纤维素(NCC)对磷酸钙骨水泥(CPC)抗压强度的影响。采用万能力学试验机、Gilmore双针、X射线衍射仪(XRD)和X射线光电子能谱仪(XPS)表征含不同NCC的CPC理化性能; 利用扫描电子显微镜(SEM)和荧光显微镜观察CPC断面形貌和荧光标记的NCC在CPC中的分散。抗压强度结果表明: NCC能显著提高CPC的抗压强度, 且2% NCC-CPC的抗压强度最高, 约为27 MPa; CPC的凝固时间随NCC含量的增加而延长, 含量为2%时基本符合临床要求; XRD和XPS结果显示NCC与Ca²⁺形成不稳定的配合物, 促进了CPC中二水磷酸氢钙(DCPD)和CaCO₃的溶解和转化; SEM观察结果显示加入NCC使CPC内部结构更致密, 孔隙和裂纹减少; 荧光显微观察结果表明NCC在CPC中均匀分散。     

载不同浓度香丹注射液磷酸钙骨水泥性能研究

研究载不同浓度香丹注射液(简称香丹)磷酸钙骨水泥(CPC)的理化性能和药物释放,为优化CPC中载入香丹浓度提供理论依据.将香丹与CPC主要原料之一磷酸氢钙混合烘干代替磷酸氢钙制得一系列载不同浓度香丹的CPC,香丹浓度范围在0.05～0.5mL/g.采用Gilmore针、万能材料力学试验机、X射线衍射仪、傅立叶红外光谱仪表征载不同浓度香丹CPC的理化性能,用扫描电镜观察微观形貌,测定载不同浓度香丹CPC的药物释放.结果表明CPC凝结时间随香丹浓度的增加而延长,浓度不高于0.2mL/g的CPC样品凝结时间符合临床要求;抗压强度随香丹含量的增加而增加;香丹加入对CPC转化没有明显影响,但导致水化产物晶体形貌从颗粒状松散搭接转化为片状交织,且浓度越高片状晶体越多.在药物释放的最初4h,载入香丹浓度范围为0.1～0.5mL/g的CPC其释药量符合临床需要.因此,载入香丹浓度范围为0.1～0.2mL/g的CPC凝结时间符合临床要求,比空白CPC具有更高的抗压强度,在初阶段药物释放量符合治疗需求.     

Improvement of Mechanical Properties of Self Setting Calcium Phosphate Bone Cements Mixed With Different Metal Oxides

Calcium phosphate cements (CPC), based on multicomponent powder mixtures of calcium orthophosphates with medium particle sizes in the region of 1 ‐ 20 μm, set isothermally in an aqueous environment to form hydroxyapatite (HA). HA cement reactants include tetracalcium phosphate (TTCP), tricalcium phosphate (TCP), dicalcium phosphate anhydrate (DCPA), dicalcium phosphate dihydrate (DCPD), monocalcium phosphate (MCPA) or octacalcium phosphate (OCP). The aim of this study was to improve the mechanical performance of TTCP / DCPA cement by adding several metal oxides to tetracalcium phosphate during the fabrication process. Cements based on tetracalcium phosphate mixed with silica or titanium oxide showed significant increases in compressive strength, approximately 80 ‐ 100 MPa, whilst no change in the mechanical behavior of CPC was observed if zirconia was added. X‐ray diffraction measurement confirmed the setting reaction of doped cements was similar to that of pure CPC. Low crystalline HA was found to be the main constituant of set cement; additional phases, such as calcium titanate or calcium zirconate, were not involved in the reaction. A mechanical reinforcement effect was thought to result from changes in the thermodynamic or kinetic solubilities of doped tetracalcium phosphates, this would lead to slower HA crystal formation and a more cross‐linked cement structure.     

Physicochemical Properties of Calcium Phosphate–Chitosan Composites and Scaffolds

This paper reports a study of the physicochemical properties of composites and scaffolds (synthesized for the first time) based on dicalcium phosphate dihydrate (DCPD, brushite), hydroxyapatite (HA), and chitosan. The crystallite size of the composites has been shown to increase with increasing chitosan concentration in the starting solution. The first technique has been proposed for the fabrication of scaffolds based on brushite, HA, and chitosan gel. The pore size in the scaffolds has been shown to increase with increasing brushite content. Raising the calcination temperature improves the stability of the scaffolds, whereas the composites persist in the form of powder independent of heat treatment. Analysis of the dissolution behavior of the synthesized composites and scaffolds in an isotonic solution indicates that, in the DCPD–chitosan system, the dissolution rate decreases with increasing chitosan concentration, whereas the HA–chitosan system exhibits opposite behavior.     

载香丹磷酸氢钙的研究

研究了湿法合成对香丹和磷酸氢钙的影响,以及温度和香丹添加量对磷酸氢钙载药量的影响.结果表明,湿法合成对香丹和磷酸钙氢钙均无明显影响,温度对香丹载入量影响较小,香丹载入量与合成体系中香丹添加量成正比.通过湿法合成制备载不同浓度香丹磷酸氢钙具有可行性.     

丝素纤维强化磷酸钙骨水泥的性能

采用在磷酸钙骨水泥(CPC)中掺入丝素纤维(SFF)来强化CPC。用X射线衍射(XRD)、红外光谱(FT-IR)研究材料的结构,用ISO水泥标准维卡仪测定CPC的凝固时间,用扫描电镜(SEM)观察材料的表面形态,在Instron上测定样品的力学性能。结果表明,CPC中的磷酸三钙和磷酸氢钙在固化过程中基本上转化为羟基磷灰石,SFF的加入加快了磷酸氢钙的转化。CPC的凝固时间随着掺入SFF含量的增加而缩短;弯曲强度和弯曲断裂功均随着SFF含量的增加而增加,尤其弯曲断裂功增加显著,但当SFF含量大于1.5%,两者均随着SFF含量的增加而所下降,但均比纯CPC的高;在CPC中加入1.5%的SFF,压缩强度和压缩断裂功均明显比纯CPC的高。     

二水磷酸氢钙包覆镁粉的组织及其在NaCl溶液中的腐蚀行为

运用液相化学沉积技术制备了二水磷酸氢钙包覆镁粉粉末。利用扫描电镜(SEM)、能谱仪(EDS)、X射线衍射仪(XRD)及傅里叶变换红外光谱仪(FT-IR)分析包覆层特征,用比表面积和孔隙度分析仪测定包覆前后粉末的比表面积,并通过浸泡实验研究包覆粉末的腐蚀行为。结果表明,包覆处理后的镁粉颗粒仍保持球形,表面形成了一层厚度2~4μm细片状的二水磷酸氢钙(DCPD),与未包覆粉末相比,其比表面积增加约60倍,在3.5%(质量分数)NaCl溶液中的耐腐蚀性能提高四个数量级。     

Design and Development of a Fluidized Bed for the Size Classification of Microgranular Dicalcium Phosphate

Brazil is the world's second largest producer of dicalcium phosphate, which is the main source of dietary phosphorus that complements the mineral salts contained in cattle, pig and poultry feed. The natural sources of dicalcium phosphate are not homogeneous and a final product classification process is required to ensure compliance with the physical specifications of the product shipped to clients. The objective of this work is to study a classification system for dicalcium phosphate using fluidization. A statistical analysis of the main experimental results using factorial planning and multiple regressions yielded parameters for the individual variables and the interactions among them. The model is validated by means of eight experiments performed in a pilot fluidized bed. The separation and recovery efficiencies obtained with the pilot system demonstrate the excellent technological application of the proposed dicalcium phosphate classification.     

磷酸四钙合成机理及其稳定性研究

本文讨论了直接固相反应法制备磷酸四钙的工艺过程,证明原料在煅烧过程中先生成了羟基磷灰石,接着在更高的温度由羟基磷灰石分解产生磷酸四钙.同时还发现磷酸四钙在潮湿和高温环境下均会转变为羟基磷灰石.     

Synthesis and characterization of nano-crystalline calcium phosphates with EDTA-assisted hydrothermal method

This study aims to prepare the biologically important hydroxyapatite (HA), dicalcium phosphate dihydrate (DCPD) and dicalcium phosphate anhydrous (DCPA) phases in simple EDTA – assisted hydrothermal method. X-ray diffraction results showed that pure DCPD, DCPA and HA nano-crystals were obtained in the Ca–EDTA/PO₄ solutions at 120 °C, 180 °C and 210 °C, respectively. Thermal gravimetric analysis of the DCPD precipitates revealed that phase transformations of DCPD to DCPA and DCPA to HA occurred at 139 °C and 195 °C, respectively, which resulted in the different Ca–P phases during hydrothermal synthesis at different temperature ranges.     

Properties of Calcium Phosphate Cements With Different Tetracalcium Phosphate and Dicalcium Phosphate Anhydrous Molar Ratios

Calcium phosphate cements (CPCs) were prepared using mixtures of tetracalcium phosphate (TTCP) and dicalcium phosphate anhydrous (DCPA), with TTCP/DCPA molar ratios of 1/1, 1/2, or 1/3, with the powder and water as the liquid. Diametral tensile strength (DTS), porosity, and phase composition (powder x-ray diffraction) were determined after the set specimens have been immersed in a physiological-like solution (PLS) for 1 d, 5 d, and 10 d. Cement dissolution rates in an acidified PLS were measured using a dual constant composition method. Setting times ((30 ± 1) min) were the same for all cements. DTS decreased with decreasing TTCP/DCPA ratio and, in some cases, also decreased with PLS immersion time. Porosity and hydroxyapatite (HA) formation increased with PLS immersion time. Cements with TTCP/DCPA ratios of 1/2 and 1/3, which formed calcium-deficient HA, dissolved more rapidly than the cement with a ratio of 1/1. In conclusion, cements may be prepared with a range of TTCP/DCPA ratios, and those with lower ratio had lower strengths but dissolved more rapidly in acidified PLS.     

Investigation of Phase Evolution During the Thermochemical Synthesis of Tricalcium Phosphate

The formation of tricalcium phosphate (TCP) from dicalcium phosphate and calcium carbonate was investigated using differential thermal analysis (DTA), thermogravimetric analysis (TGA), and powder X-ray diffraction (XRD). DTA showed three distinct thermal events attributed to dehydration of dicalcium phosphate dihydrate (brushite, DCPD) to dicalcium phosphate anhydrous (monetite, DCPA), the formation of beta-calcium pyrophosphate (-Ca₂P₂O₇), and the calcination of calcium carbonate. TGA showed three weight losses corresponding to the three thermal events, respectively. XRD analysis showed that -TCP formed, beginning at about 900°C, by the reaction of -Ca₂P₂O₇ with CaO and -TCP changed to -TCP above 1200°C. Further examination of the formation of TCP from calcium hydroxide (Ca(OH)₂) and DCPA showed that -TCP would form only after the decomposition of Ca(OH)₂ to CaO and from the reaction of CaO with -Ca₂P₂O₇ at a fairly low temperature of 800°C. In addition, by naturally cooling -TCP, formed at 1300°C within the heating furnace, to room temperature, it was difficult to obtain a pure phase of -TCP. The proposed mechanism of the reaction to form TCP may include the dehydration of brushite to monetite, dehydration of monetite to beta-calcium pyrophosphate, decomposition of calcium carbonate, the formation of -TCP, and phase transition.     

“Fabrication of arbitrarily shaped carbonate apatite foam based on the interlocking process of dicalcium hydrogen phosphate dihydrate”

Carbonate apatite (CO₃Ap) foam with an interconnected porous structure is highly attractive as a scaffold for bone replacement. In this study, arbitrarily shaped CO₃Ap foam was formed from α-tricalcium phosphate (α-TCP) foam granules via a two-step process involving treatment with acidic calcium phosphate solution followed by hydrothermal treatment with NaHCO₃. The treatment with acidic calcium phosphate solution, which is key to fabricating arbitrarily shaped CO₃Ap foam, enables dicalcium hydrogen phosphate dihydrate (DCPD) crystals to form on the α-TCP foam granules. The generated DCPD crystals cause the α-TCP granules to interlock with each other, inducing an α-TCP/DCPD foam. The interlocking structure containing DCPD crystals can survive hydrothermal treatment with NaHCO₃. The arbitrarily shaped CO₃Ap foam was fabricated from the α-TCP/DCPD foam via hydrothermal treatment at 200?°C for 24?h in the presence of a large amount of NaHCO₃.     

A novel in situ synthesis of dicalcium phosphate dehydrate nanocrystals in biodegradable polymer matrix

In the paper, we found a novel method to synthesize dicalcium phosphate dehydrate (DCPD) nanocrystals by in situ reaction in biodegradable PDLLA matrix. Calcium hydrid was selected as calcium source of DCPD, which is different from general methods. The method is not only simple and effective to synthesize Ca–P particles, but also can avoid the aggregation of inorganic nanoparticles in the course of their being dispersed into polymer matrix.     

A comparison of trehalose dihydrate and mannitol as stabilizing agents for dicalcium phosphate dihydrate based tablets

This study investigated the possible utility of trehalose dihydrate (TD) as a tablet stabilizing agent. Acetylsalicylic acid was used as the model hydrolyzable drug and dicalcium phosphate dihydrate (DCPD) as the base excipient, because it is well documented that ASA/DCPD tablets are unstable during storage at low temperature and high relative humidity; DCPD is usually combined with mannitol in order to improve tablet stability. Tablets comprising DCPD, 10% ASA, and 0%, 10%, or 20% w/w of TD were prepared by direct compression and stored at 35 degrees C and 82.9% relative humidity for 6 months. Additionally, control tablets with DCPD and ASA, only, or with DCPD, ASA and 20% mannitol, were also evaluated. At predetermined time intervals, formulations were tested for drug content, mechanical, microstructural, and drug dissolution properties. Additionally, thermal analyses and ASA solution stability studies were carried out. Results reveal that both TD and mannitol significantly reduce degradation of ASA included in DCPD-based tablets, but neither effectively protects against the marked decline in tablet mechanical properties on aging. The ASA stabilization effects of TD and mannitol were also observed in solution, indicating an interaction between these sugars and ASA.     

Use of Dicalcium Phosphate Dihydrate for Sustained Release of Highly Water Soluble Drugs

The utilituy of Dicalcium phosphate dihydrate (DCPD), a commonly used water insoluble pharmaceutical excipient, has been investigated for its use in formulating a controlled release matrix type tablet for highly water soluble drugs. Various drugs were formulated into a tablet by direcly compressing mixture of the drug, dicalcium phosphate dihydrate, and magnecium stearate on a single punch tablet machine. Effects of drug concentation and tablet weight on the release profiles were studied using USP II dissolution machine.

The release from these matrices followed first order kinetics rather than square root time rule. The release profile and the first order rate constant seemed to be dependent upon the the size of the tablet. Incorporation of drug in a quantity excess of 5% w/w of the tablet resulted in disintegration of the tablet and subsequent rapid release of the drug.

Dicalcium phosphate may be a simpler, cheaper, and a viable way to formulating directly compressible sustained release formulations.     

On the development of an apatitic calcium phosphate bone cement

Development of an apatitic calcium phosphate bone cement is reported. 100 μ Particles of tetracalcium phosphate (TTCP) and dicalcium phosphate dihydrate (DCPD) were mixed in equimolar ratio to form the cement powder. The wetting medium used was distilled water with Na₂HPO₄ as accelerator to manipulate the setting time. The cement powder, on wetting with the medium, formed a workable putty. The setting times of the putty were measured using a Vicat type apparatus and the compressive strength was determined with a Universal Testing Machine. The nature of the precipitated cement was analyzed through X-ray diffraction (XRD), fourier transform infrared spectrometry (FTIR) and energy dispersive electron microprobe (EDAX). The results showed the phase to be apatitic with a calcium-to-phosphorous ratio close to that of hydroxyapatite. The microstructure analysis using scanning electron microscopy (SEM) showed hydroxyapatite nano-crystallite growth over particulate matrix surface. The structure has an apparent porosity of ∼ 52%. There were no appreciable dimensional or thermal changes during setting. The cement passed the in vitro toxicological screening (cytotoxicity and haemolysis) tests. Optimization of the cement was done by manipulating the accelerator concentration so that the setting time, hardening time and the compressive strength had clinically relevant values.