AU2021106547A4 - Improved Sono-chemical Synthesis of Hydroxyapatite Nanorods As A Dental Restorer Filler Materials - Google Patents

Abstract

of Patent Solid hydroxyapatite micro and nanoparticles are important sub millimeter structures with several novel properties compared to its bulk counterparts and can be utilized in many fields. These materials can be used in hard tissue engineering. The present invention relates to development of a dental filling material which (a) structurally mimics the natural tooth enamel, (b) reduces processing time involving innovative ultra-sonication and microwave radiations, (c) potential to re-mineralize the natural tooth enamel on application to a dental tissue. The sonochemical methodology presented here ensures an eco-friendly, facile, and effective method to produce bulk (kg) amounts of highly stable hydroxyapatite solid micro/nanoparticles. These can be engineered also by varying the concentration of chemicals. This green chemistry method is cleaner, non toxic and efficient. Hydroxyapatite (HAP) can be engineered to produce fluorapatite, chlorapatite or carbonated apatite by substitution reaction with fluoride, chloride or carbonate ions. The method presented here showed that polygonal hydroxyapatite rods can be indeed engineered by the sonochemical method.

Description

EDITORIAL NOTE 2021106547

There are 8 pages of description only.

Improved Sono-chemical Synthesis of Hydroxyapatite Nanorod As A Dental Restorer Filler Materials

Technical Area

[0001] The manufacturing process relates to the technical area of preparing a dental filler material/cement using hydroxyapatite doped with essential ions to enhance the compositional affinity and mimic the biological apatite nano-crystals of alveolar bone/teeth.

[0002] The use of ultrasonication and microwave technique not only improved the synthesis of nanorods but also reduced the reaction time by the use of ultrasound cavitation with much higher temperatures at the in situ reaction sites within the reaction system.

[0003] Nano/micro particles display unique physicochemical and biological characteristics. Efficient production of hydroxyapatite-HAP micro/nano particles is now required in a range of applications following recent advances in nanotechnology in different fields such as biomedical. This utility model relates to the method of facile production of polygonal Calcium based apaptite 3 structures from a molecular level by applying chemical principles of sonochemical synthesis and subsequent thermal treatment.

Background

[0001] Even today, access to good dental care is a worldwide problem with most large populations having minimal access to dental care. The mouth is a very hostile environment as teeth are constantly being eroded by mastication of food. Furthermore, the human mouth is also the host for a variety of bacterial colonies that cannot be eradicated. These cariogenic biofilms constantly produce acid that creates a corrosive environment for the tooth's enamel and underlying matrix of hydroxyapatite. Caries have a high incidence of disease with about 100% of the human population being affected. India, China and Brazil are places where dental diseases are reaching epidemic proportions [1]. While in advanced countries, the switch to elevated levels of HFCS, -high levels fructose Corn syrup in drinks and foods as well as the increased consumption of bottle water (with less fluoride) has combined to make this disease prevalent in large numbers.

[0002] Bone is a natural organic-inorganic ceramic composite consisting of collagen fibrils with embedded well-arrayed inorganic nano crystalline rod and plate like shaped material ranging in size from 25 to 50 nm in length [2, 3]. Hydroxyapatite (HAP) is the main inorganic component of bone and teeth; it's a mineral composed of calcium phosphate which has the general formula of [Caio (OH) 2 (P0 4 )6 ]. HAP crystal has a close chemical similarity to natural bone and it has led to extensive research efforts to employ synthetic HAP as a bone substitute and/or replacement in several clinical procedures [4, 5]. Dental enamel forms a hierarchical material composed primarily of hydroxyapatite nanorods. The biological forms of apatite are nonstoichiometric and also contain small amounts of beneficial materials like fluoride, magnesium, potassium and sulphate.

[0003] There are several advantages in using synthetic HAP; it has good biocompatibility to body tissues, it has a slow biodegradability in situ, it also offers good osteoconductivity and osteoinductivity capabilities [6-8]. An investigation by Taniguchi et al [9] has shown that sintered HAP exhibited an excellent biocompatible response to soft tissue such as skin, muscle and gums. It is this type of response that made synthetic HAP an ideal candidate for orthopaedic and dental implants. This is the also reason why synthetic HAP has been widely used in hard tissues applications such as; bone repair, bone augmentation, the coating of metal implants and used as a filling material in both bone and teeth [10 12]. However, because of its low mechanical strength the use of pure HAP ceramics is generally restricted to low load bearing applications. In some cases, these deficiencies can be alleviated by combining HAP with other materials such as polymers and/or glass to form a composite. Materials such as high-density polyethylene and polypropylene can be used to improve the load bearing capabilities of HAP [13, 14].

[0004] Historically, several techniques have been developed and used to manufacture HAP and calcium phosphate ceramics. These diverse techniques include homogeneous precipitation [15, 16], sol-gel [17], plasma spray [18], hydrothermal [19] and ultrasonic spray freeze drying

[20] processes. The most attractive technique mentioned above is the sol-gel process; this wet chemical method is based on a simplest and straight forward procedure that can economically produce HAP without the need for expensive specialised equipment. Moreover, this technique can be easily scaled up to meet high demands. However, the main difficulty in using this technique is in controlling the size and the morphology of the resulting nanoparticles to be within a small parameter range. This fine-tuning of the size and morphology is crucial in determining the properties of the resulting nano-HAP.

[0005] Wet chemical techniques have been used to produce crystalline materials from solutions, but a subsequent thermal treatment at elevated temperatures is required to produce specific crystalline phases. The particle size and morphology of HAP based dental fillers produced using this technique can be controlled by varying the experimental conditions that regulate nucleation, aging process and the growth kinetics of the particles. The controlling parameters that are used to produce mono phase HAP are the initial reactants, the preparation temperature and the pH value. It should also be mentioned that the electronic properties of HAP are sensitive to several variables such as Ca/P ratios, structural defects, crystal size, temperature and the preparation procedures used to produce the HAP [21]. Furthermore, Sonochemical and thermally driven combination processes to generate crystalline nanohydroxyapatite ultrafine powders (nanospheres) have been successfully demonstrated in a number of studies by the authors, [21-26]

Summary of the Invention

[0001] The current invention is aimed at the facile preparation Calcium based hydroxyapatite nanoparticles and micron sized particles via a wet reaction pathway enhanced by ultrasounds action to solve the ubiquitous method of simply heating the reaction mixture.

[0002] The action of the cavitation and implosion of bubbles in the reaction mixtures ensures a fast and efficient way to prepare materials in a proportional manner as the size of the cavitation implosion creates hotspot forthe reaction and also allows fast mixing to drive the reaction and this is highly regulated by controlling the reaction parameters related to this process.

[0003] The current invention is aimed at the preparation of hydroxyapatite based dental restorative fillings with added minerals, to enhance the natural re-mineralization process.

TECHNICAL SOLUTION TO ACHIEVE THE ABOVE OBJECT To manufacture the restorative ceramic powders for dental filling is as follows:

[0001] Step 1: Preparation of seeding Solution A: 10ml of 0.32M Ca(N0 3) 2 4H 20 mixed with 10ml of 0.19M K 2 CO3 into a beaker and white precipitates formed were allowed to settle

[0002] Step 2: Preparation of Solution B: This formulation began by decanting a 30 mL solution of 0.32M Ca(N0 3 ) 2 .4H 2 0 into a small beaker followed by addition of 5 mL of NH 4 0H solution. In order to maintain the pH of solution above 9, ammonia was added at regular intervals. Then a mL solution of 0.19M KH 2 PO 4 was slowly added drop-wise to the above solution under ultrasonic irradiation conditions. The ultrasound processor used was a UP400S supplied by Hielscher Ultrasound Technology (Teltow, Germany). The processor was fitted with a 22 mm diameter sonotrode operating at 24 kHz and set to maximum amplitude and operating power of 200 W. The mixture was subjected to ultrasonic processing for 10 minutes. The solution pH was kept above 9 and the Ca/P ratio of 1.67 was maintained throughout the process. After 10 minutes of ultrasonication, ml of 0.16M MgN 20Oand 10 ml of 0.16M NH 4 F added dropwise and ultrasonication continued for another 10 minutes at 200W power.

[0003] Step 3: Mixing Solution A and B: After 10 minutes of ultrasonication and formation of precipitates, seeding Solution A was added dropwise to Solution B. The mixture was kept under ultrasonic conditions for another 2 minutes at 200W power while maintaining the pH above 9 using ammonia solution.

[0004] Step 4: Once the precipitates settle, the mixture was subjected to centrifugation at 3500 rpm for 20 minutes to separate the white precipitate that had formed during processing. Following centrifugation, the white precipitate underwent washing with Milli-Q@ water several times.

[0005] Step 5: The precipitate was then heated in a 240V and 50Hz microwave oven (Model TMOSS25) operating at 900 W and 2450 MHz for a 14-minute treatment period.

[0006] Step 6: After treatment, samples were ground to the consistency of an ultrafine powder using mortar and pestle.

The present invention will be described in more details below in conjunction with embodiments.

[0007]A seeding solution of K 2 CO3 and MgN 20 prepared followed by ultrasonication for 5 minutes at 200W operating power of ultrasonication. The formulation was followed by addition of NH 4 F dropwise under continued ultrasonication conditions. This solution mixture was added to solution B prepared by addition of Ca(N 3 ) 2 and KH 2 PO 4 while maintaining the solution pH of 9 and Ca/P ratio of 1.67.

[0008] A seeding solution of K 2 CO3 and Ca(N0 3) 2 prepared was added to solution B prepared by addition of Ca(N 3 ) 2 and KH 2 PO 4 while maintaining the solution pH of 9 and Ca/P ratio of 1.67. The fluoride (NH 4 F) and magnesium (MgN 20) ion concentration was enhanced while maintaining the molar proportions.

[0009] In this description, specific examples are used to define the principle and significance of seeding solution in the present invention. While the basic idea of the invention will vary depending on the specific implementation of its field of application.

INVENTION ADVANTAGES

[0001] The synthesised dental restorative fillings with added minerals enhances the natural re-mineralization process and shows morphological similarity to hydroxyapatite rods of natural tooth enamel and dentine.

[0002] The XRD and SAED analysis indicate that the dental fillers produced by this ultrasonically mediated thermal route are of high quality.

[0003] The combined ultrasonic/microwave technique is an effective and fast process of manufacturing bulk dental filling material.

[0004] Another major advantages of using ultrasonic irradiation during the manufacture of superfine mineralized dental filler powder is the increased reaction speed, the decreased processing time and an overall improvement in the efficient use of energy.

[0005] The use of ultrasonic irradiation during wet milling forms an efficient means of dispersing and de-agglomerating the sample particles during the grinding process. The sonochemical effect which produces acoustic cavitation, promotes both chemical reactions and physical effects that directly influence the particle morphology during the growth phase.

[0006] A change in the parameters like temperature, pH, precursors, Ca/P ratio, aging time, preparation procedure makes it possible to modify and control the structure and size of HAP rods, which further determines the surface chemistry.

[0007] The change in concentration of chemicals/pH/power of ultrasounds can lead to changes in size, shape, thickness, composition and numbers in the active layer which will be conducive to the adsorption and hardness properties of this layer.

References

[1] Taubman MA, Nash DA., The scientific and public-health imperative for a vaccine against dental caries, Nat Rev Immunol. 2006 Jul; 6(7):555 63.

[2] Weiner S, Wagner HD 1998 Annual Review of Materials Science 28

[3] Hellmich C, Ulm FJ 2003 Biomechan. Model Mechanobiol. 2 21

[4] Hutmacher DW, Schantz JT, Lam CXF, Tan KC, Lim TC 2007 J. Tissue Eng Regen Med 1 245

[5] Habraken WJEM, Wolke JGC, Jansen JA, 2007 Advanced Drug Delivery Reviews 59 234

[6] Blom A 2007 Current Orthopaedics 21 280

[7] Habibovic P, de Groot K 2007 J. Tissue Eng and Regen Med 1 25

[8] Kalita SJ, Bhardwaj A, Bhatt HA 2007 Materials Science and Engineering C 27 441

[9] Taniguchi M, Takeyema H, Mizunna I, Shinagawa N, Yura J, Yoshikawa N, Aoki H, 1991 Jpn. J. Artif. Organs 20 460

[10] Silva RV, Bertran JA, Moreira NH 2005 Inter. J. Oral & Maxillofacial Surg. 34 178

[11] Stoch A, Jastrzebski W, Dlugon E, Lejda W, Trybalska B, Stoch GJ, Adamczyk A 2005 J. Molecular structure 744 633

[12] Vecchio KS, Zhang X, Massie JB, Wang M, Kim CW 2007 Acta Biomaterialia 3 910

[13] Ono I, Tateshita T, Nakajima T 2000 Biomaterials 21 143

[14] Bonner M, Ward IM 2001 J. Materials Science Letters 20 2049

[15] Santos MH, Oliveira M, Palhares de Freitas L, Mansur HS, Vasconcelos WL 2004 Materials Research 7 625

[16 ] Aizawa M, Ueno H, Itatani K, Okada I 2006 J. European Ceramic Society 26 501

[17] Panda RN, Hsieh MF, Chung RJ, Chin TS 2003 J. Physics and Chemistry of Solids 64 193

[18] Park E, Condrate RA, Lee D 1998 Materials Letters 36 38

[19] Kannan S, Rocha JHG, Agathopoulos S, Ferreira JMF 2007 Acts Biomaterialia 3 243

[20] Itatani K, Iwafune K, Howell FS, Aizawa M 2000 Materials Research Bulletin 35 575

[21] Jarudilokkul S, Tanthapanichakoon W, Boonamnuayvittaya V 2006 Colloids and Surfaces A: Physicochem. Eng. Aspects

[22] Poinern, G.E., Brundavanam, R.K., Mondinos, N. and Jiang, Z-T (2009) Synthesis and characterisation of nanohydroxyapatite using an ultrasound assisted method. Ultrasonics Sonochemistry, 16 (4). pp. 469 474.

[23] Poinern, G.E.J., Brundavanam, R.K., Le, X.T., Djordjevic, S., Prokic, M. and Fawcett, D. (2011) Thermal and ultrasonic influence in the formation of nanometer scale hydroxyapatite bio-ceramic. International Journal of Nanomedicine (6). pp. 2083-2095.

[24] Brundavanam, R.K., Jiang, Z-T, Chapman, P., Le, X., Mondinos, N., Fawcett, D. and Poinern, G.E.J. (2011) Effect of dilute gelatine on the ultrasonic thermally assisted synthesis of nano hydroxyapatite. Ultrasonics Sonochemistry, 18 (3). pp. 697-703.

[25] Rattan, S., Fawcett, D., Tennant, M., Granich, J. and Poinern, G.E.J. (2021) Progress of nanomaterials in preventative and restorative dentistry. Recent Progress in Materials, 3 (1).

[26]Rattan, S., Fawcett, D. and Poinern, G.E.J. (2021) Williamson-Hall based X-ray peak profile evaluation and nano-structural characterization of rod-shaped hydroxyapatite powder for potential dental restorative procedures. AIMS Material science, 8 (3). pp. 359-372.

EDITORIAL NOTE 2021106547

There is 1 page of claims only.

Claims (6)

1. Claims: 1. Controllability. To create precise polygonal nanorods particles, there is a need of controllability and this method, allows the nanotechnologist orscientist to finetune this process. The composition characterized in the manufactured dental restorative fillercomprises the minerals required for demineralization of enamel.
2. 2. The dental filler according to claim 1 has showed morphological similarity to natural hydroxyapatite nanocrystals as found in tooth enamel and dentine. The nano-rod crystals in synthesized powders are stacked together and distributed homogeneously in one direction as seen through non-destructive AFM analysis.
3. 3. The dental filler as described in either of claims 1 and 2 are further characterized and formed into restorative filler powders, usable in a method for filling the tooth cavities as a natural mineralized composite.
4. 4. The dental filler restorative powder offers a faster manufacturing, efficient and natural remineralized route of cavity filling and surface coating wherein the nano-rods of filler have an average particle size of 40-90nm length and 5-20nm width.
5. 5. The restorative powder according to claim 1 or 2 can also contains surface modified and doped ions (F, Mg2+, Ca2+, K, Na2+, P0 4 2 - C0 3 2 -) essential for enhancing the natural remineralization process in tooth.
6. 6. The process of manufacturing dental filler, as in either claim 1 or 2, comprises the hydrothermal precipitation in the presence of ultrasonication cavitation and then microwave thermal heating to produce nano-rods as a restorative treatment for dental issues.

   Description of figures

   Fig 1: Field Emission Scanning electron micrographs of ultrasonochemically synthesised nanohydroxyaptite restorative ceramic powder

   Fig 2: Transmission electron micrographs of ultrasonochemically synthesised nanohydroxyaptite restorative ceramic powder

   Fig.3 SAED of synthesised restorative ceramic powder

   Fig 4: HAADF-STEM image and combined elemental mapping images Ca, P, F, Na, O and Mg as present in synthesised restorative ceramic powder.

   Fig 5: Powder X-ray diffraction analysis of ultrasonochemically synthesised nanohydroxyaptite restorative ceramic powder

   18

   16

   14

   12

   10

   F(N) 8

   6

   4

   2

   0 0 0.002 0.004 0.006 0.008 0.01 0.012 0.014 0.016

   -2 Strain (mm)

   Fig 6: Force Curves of ultrasonochemically synthesised nanohydroxyaptite restorative ceramic powder

   Fig 7: Atomic force micrograph of synthesised restorative ceramic powder

   Fig 8: FT-IR of ultrasonochemically synthesised nanohydroxyaptite restorative ceramic powder showing the major hydroxyl, carbonate and phospate group in the nanorods.