Chlorhexidine crystal forms and uses thereof in medicine

Patent metadata

Field	Value
Publication number	US-10640463-B2
Application number	US-201716085489-A
Country	US
Kind code	B2
Filing date	Mar 17, 2017
Priority date	Mar 18, 2016
Publication date	May 5, 2020
Grant date	May 5, 2020

Abstract

The present invention provides a crystalline salt of chlorhexidine chloride having a spherical morphology under Scanning Electron Microscopy (SEM) comprising a chloride anion and a cation selected from the group consisting of calcium, sodium, potassium, magnesium, zinc, strontium or iron, processes for the preparation of the salt, compositions, pharmaceutical compositions and uses thereof in medicine. Also provided are crystalline forms of the salt and fibres comprising the same.

First claim

The invention claimed is:

1. A crystalline salt of chlorhexidine chloride having a spherical morphology under Scanning Electron Microscopy (SEM) comprising a chloride anion and a cation comprising calcium, wherein the crystalline salt has an X-ray diffraction pattern comprising peaks, in terms of 2-theta, at about 8.50, about 13.40, about 15.90, about 20.90, about 23.70, and about 26.60.

2. Monodisperse crystals of a crystalline salt of chlorhexidine chloride according to claim 1 .

3. A process for the preparation of monodisperse crystals of a crystalline chlorhexidine chloride salt of claim 2 , comprising
(i) mixing an aqueous solution of chlorhexidine acetate with an aqueous solution of a metal chloride of the formula (MCl x ), where x is equal to 1 or 2, at a concentration of 0.1M to 1.0M;
(ii) allowing the chlorhexidine chloride salt to precipitate;
(iii) centrifuging the precipitate formed in (ii) to obtain a solid mass of precipitated salt crystals; and
(iv) washing the precipitated solid mass of (iii).

4. A process as claimed in claim 3 , further comprising introducing emulsions, colloids, micro or nano-scale inorganic or metallic oxides into the aqueous solution of chlorhexidine acetate in step (i).

5. A crystalline chlorhexidine chloride salt prepared by a process according to claim 3 .

6. A cement composition comprising a crystalline salt of chlorhexidine chloride according to claim 1 .

7. A pharmaceutical composition comprising a crystalline chlorhexidine chloride salt according to claim 1 .

8. A composition comprising a crystalline chlorhexidine chloride salt according to claim 1 encapsulated or suspended in a polyelectrolyte, or in a polymerizable monomer.

9. A composition as claimed in claim 8 , in which the polymerizable monomer comprises a methacrylate.

10. A composition as claimed in claim 8 , in which the polymerizable monomer comprises a dimethacrylate monomer.

11. A composition as claimed in claim 9 , in which the polymerizable monomer comprises a hydrophilic monomer.

12. A composition as claimed in claim 8 , in which the polyelectrolyte is polylactic acid (PLA).

13. A composition comprising a bioactive glass composed of at least two or more compounds selected from the group consisting of SiO 2 , CaO, CaF 2 , SrF 2 , SrO, MgO, ZnO, K 2 O, B 2 O 3 , ZnO, PO 3 , P 2 O 5 , NaF, CaCl 2 and NaCl and a crystalline form of a chlorhexidine chloride salt according to claim 1 .

14. A composition as claimed in claim 13 , further comprising silica.

15. A composition comprising a metal or metal oxide particle of mean average particle diameter size 10 to 50 nm and a crystalline chlorhexidine chloride salt according to claim 1 .

16. A composition of claim 15 encapsulated or suspended in a polyelectrolyte, or a polymerizable monomer.

17. A composition as claimed in claim 15 , further comprising a polyelectrolyte.

18. A composition as claimed in claim 8 , further comprising a photoinitiator.

19. A crystalline chlorhexidine chloride salt according to claim 1 in the form of a mouthwash, toothpaste, gel or polymer.

20. A natural or synthetic fibre further comprising a crystalline chlorhexidine chloride salt according to claim 1 .

21. A natural or synthetic fibre as claimed in claim 20 selected from the group consisting of cellulose, cotton, polyurethane and nylon.

Assignees

• Univ London Queen Mary

Inventors

• Cattel Michael
• Sukhorukov Gleb
• Shahid Saroash
• Luo Dong

Classifications

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• C07C279/265 Primary

  containing two or more biguanide groups · CPC title

• A61P31/04

  Antibacterial agents · CPC title