Process for obtaining fluoride-doped citrate-coated amorphous calcium phosphate nanoparticles

Patent metadata

Field	Value
Publication number	US-10105390-B2
Application number	US-201515327817-A
Country	US
Kind code	B2
Filing date	Jul 21, 2015
Priority date	Jul 21, 2014
Publication date	Oct 23, 2018
Grant date	Oct 23, 2018

Abstract

Process for obtaining fluoride-doped citrate-coated amorphous calcium phosphate nanoparticles. This material has applications in biomedicine due to its biodegradability and bioactivity; it also promotes cell adhesion and osteogeneration. In dentistry, it may be used in toothpastes, mouthwashes, chewing gums, gels and fluoride varnishes as a remineralising agent of dentine and enamel. It is based on two solutions formed by calcium chloride and sodium citrate on the one hand, and by sodium monohydrogenophosphate and sodium carbonate with a fluoride compound on the other, which are mixed at room temperature. The process is eco-efficient and eco-friendly, as it does not leave any acid residue; it consists of a single stage and it is the first time that an amorphous calcium phosphate coated with citrate and doped with fluoride, which enhances its remineralising action, is obtained.

First claim

The invention claimed is:

1. A process for obtaining fluoride-doped citrate-coated amorphous calcium phosphate nanoparticles comprising:
preparing a first solution comprising CaCl 2 at a concentration comprised between 0.08 M and 0.12 M and Na 3 C 6 H 5 O 7 at a concentration comprised between 0.35 M and 0.50 M;
preparing a second solution comprising Na 2 HPO 4 at a concentration comprised between 0.10 M and 0.15 M, Na 2 CO 3 at a concentration of 0.2 M and a fluoride compound;
mixing under stirring the two solutions prepared in the previous stages in the proportion 1:1 v/v at a pH comprised between 8.3 and 8.7 at ambient temperature for a time period of less than 2 minutes;
performing three successive sedimentation cycles of the mixture of the two solutions formed in the previous step by centrifugation, removal of the obtained supernatant and washing of the obtained precipitate using ultrapure water; and
freeze-drying the wet precipitate obtained in the previous step.

2. The process according to claim 1 , characterised in that the concentrations used for the first solution are 0.1 M for CaCl 2 and 0.4 M for Na 3 C 6 H 5 O 7 .

3. The process according to claim 1 , characterised in that the concentrations used for the second solution are 0.12 M for Na 2 HPO 4 and 0.2 M for Na 2 CO 3 .

4. The process according to claim 1 , characterised in that the fluoride compound is selected from among CaF 2 , NaF and KF and is added to a concentration comprised between 0.01 M and 0.1 M.

5. The process according to claim 4 , characterised in that the fluoride compound is CaF 2 which is added to a concentration of 0.05 M.

6. Citrate-coated and fluoride-doped amorphous calcium phosphate nanoparticles obtained by a process comprising:
preparing a first solution comprising CaCl 2 at a concentration comprised between 0.08 M and 0.12 M and Na 3 C 6 H 5 O 7 at a concentration comprised between 0.35 M and 0.50 M;
preparing a second solution comprising Na 2 HPO 4 at a concentration comprised between 0.10 M and 0.15 M, Na 2 CO 3 at a concentration of 0.2 M, and a fluoride compound;
mixing under stirring the two solutions prepared in the previous stages in the proportion 1:1 v/v at a pH comprised between 8.3 and 8.7 at ambient temperature for a time period of less than 2 minutes;
performing three successive sedimentation cycles of the mixture of the two solutions formed in the previous step by centrifugation, removal of the obtained supernatant and washing of the obtained precipitate using ultrapure water; and
freeze-drying the wet precipitate obtained in the previous step, characterised in that they have a spherical shape and a size comprised between 30 nm and 80 nm and sodium, calcium, and phosphate, citrate, carbonate, fluoride and water content comprised:
between 3.1% and 3.5% by weight of sodium
between 27.0% and 27.4% by weight of calcium
between 37.0% and 37.8% by weight of phosphate (P)
between 3.5% and 5.0% by weight of citrate
between 5.4% and 7.0% by weight of carbonate
between 6% and 10% by weight of water, and
between 2% and 5% by weight of fluoride.

7. A vehicle for biomolecules, drugs, or both comprising the citrate-coated and fluoride-doped amorphous calcium phosphate nanoparticles as defined in claim 6 .

8. A biomaterial comprising the fluoride-doped citrate-coated amorphous calcium phosphate nanoparticles as defined in claim 6 .

9. The biomaterial according to claim 8 , wherein the biomaterial is orthopaedic or dental.

10. A composition comprising the citrate-coated and fluoride-doped amorphous calcium phosphate nanoparticles as defined in claim 6 .

11. The composition according to claim 10 , wherein the composition is toothpaste, chewing gum, mouthwash, fluoride varnish, or gel.

Assignees

• Consejo Superior Investigacion
• Consiglio Nazionale Ricerche

Inventors

• Delgado Lopez Jose Manuel
• Gomez Morales Jaime
• Fernandez Penas Raquel
• Iafisco Michele
• Tampieri Anna
• Panseri Silvia

Classifications

• A61K6/864

  Phosphate cements (apatite A61K6/838) · CPC title

• A61K6/17 Primary

  Particle size · CPC title

• A61K6/54

  Filling; Sealing · CPC title

• A61K6/20

  Protective coatings for natural or artificial teeth, e.g. sealings, dye coatings or varnish · CPC title

• A61K9/5192 Primary

  Processes · CPC title