Amorphous magnesium-substituted calcium phosphate compositions and their uses

Patent metadata

Field	Value
Publication number	US-2016235683-A1
Application number	US-201415033750-A
Country	US
Kind code	A1
Filing date	Aug 28, 2014
Priority date	Nov 5, 2013
Publication date	Aug 18, 2016
Grant date	—

Abstract

Amorphous magnesium-substituted calcium, phosphate compositions and their medical uses are described, in particular for use in delivering cargo materials, such as cargo molecules or cargo nanoparticles contained in pores of the amorphous magnesium-substituted calcium phosphate to cells of the immune system, for example as therapeutic approaches for the treatment of inflammatory bowel diseases, and in particular Crohn's disease, autoimmune diseases, allergy and for therapeutic vaccination.

First claim

1 .- 3 . (canceled)

4 . A method of treating or preventing a condition by delivering a biologically active cargo material to the gastrointestinal tract, the method comprising administering to a subject in need of treatment a composition comprising amorphous magnesium-substituted calcium phosphate (AMCP) which entraps the biologically active cargo material, thereby enabling the cargo material to be delivered to a site of interest in the gastrointestinal tract.

5 . The method of treatment of claim 4 , wherein the magnesium-substituted calcium phosphate is amorphous as determined by X-ray diffraction.

6 . The method of treatment of claim 4 , wherein the X-ray diffraction pattern of the amorphous magnesium-substituted calcium phosphate is broad and diffuse with a maximum at 25 degree 2 theta.

7 . The method of treatment of claim 4 , wherein the X-ray diffraction pattern of the amorphous magnesium-substituted calcium phosphate lacks one or more peaks associated with the X-ray diffraction pattern of crystalline hydroxyapatite.

8 . The method of treatment of claim 4 , wherein the amorphous magnesium-substituted calcium phosphate is capable of dispersing to form nanoparticles that are capable of uptake by cells in the gastrointestinal tract.

9 . The method of treatment or the method of treatment of claim 8 , wherein the nanoparticles are capable of uptake by gut mucosal immune cells.

10 . (canceled)

11 . The method of treatment of claim 4 , wherein the composition delivers the biologically active cargo material to Peyer's patches or to Mesenteric Lymph Nodes (MLN).

12 .- 15 . (canceled)

16 . The method of treatment of claim 4 , wherein the amorphous magnesium-substituted calcium phosphate is administered for treating an autoimmune disease said autoimmune disease being selected from the group of Crohn's disease, celiac disease or other inflammatory bowel disease, cancer, food allergies and/or intolerances.

17 .- 18 . (canceled)

19 . The method of treatment of claim 4 , wherein the amorphous magnesium-substituted calcium phosphate is administered for use in a method of vaccinating a subject and the biologically active cargo molecule is a therapeutic vaccine composition.

20 . The composition method of treatment of claim 19 , wherein the therapeutic vaccine composition is administered for the treatment or prevention of (i) cancer; (ii) an autoimmune diseases, wherein the vaccine composition is capable of inducing tolerance towards autoimmune T cell and auto-antibody responses; (iii) inflammatory bowel disease; (iv) type 1 diabetes; and (v) systemic Lupus Erythematosus (SLE).

21 . The composition for use in a method of treatment or the method of treatment of claim 20 , wherein the cancer is a Myeloid Leukaemia.

22 . (canceled)

23 . The method of treatment of claim 20 , wherein the autoimmune condition is multiple sclerosis.

24 . (canceled)

25 . The method of treatment of claim 20 , wherein the inflammatory bowel disease is Crohn's disease or coeliac disease.

26 .- 28 . (canceled)

29 . The method of treatment of claim 4 , wherein the amorphous magnesium-substituted calcium phosphate comprises aggregated nanoparticles that are capable of dispersing to deliver the biologically active cargo molecule to the site of interest.

30 . The method of treatment of claim 29 , wherein the nanoparticles are metal-based nanoparticles or metal oxo-hydroxide based nanoparticles.

31 . The method of treatment of claim 4 , wherein the amorphous magnesium-substituted calcium phosphate is a silent delivery platform that does not cause an adjuvant response to the amorphous magnesium-substituted calcium phosphate at the site of interest that differs substantially to the response to the biologically active cargo material alone.

32 . The composition the method of treatment of claim 4 , wherein the amorphous magnesium-substituted calcium phosphate is a silent delivery platform that does not cause a direct transcriptional response to the amorphous magnesium-substituted calcium phosphate at the site of interest.

33 . (canceled)

34 . The method of treatment of claim 4 , wherein the ratio of Mg:Ca in the amorphous magnesium-substituted calcium phosphate is at least 1:25, more preferably at least 1:20, more preferably at least 1:10, more preferably at least 1:5, more preferably at least 1:4 and most preferably 1:3.

35 .- 40 . (canceled)

41 . The method of treatment of claim 4 , wherein the cargo material is selected from the group consisting of protein antigens, bioactive cytokines, peptidoglycans, low molecular weight organic molecules and nanoparticles.

42 . (canceled)

43 . The method of treatment of claim 4 , wherein the cargo material is a nutrient, a nanoparticle, therapeutic molecule, vaccine, a nucleic acid molecule, such as DNA or RNA.

44 .- 47 (canceled)

48 . A method of diagnosis or imaging, wherein the method comprises administering an amorphous magnesium-substituted calcium phosphate (AMCP), wherein the amorphous magnesium-substituted calcium phosphate entraps a detectable moiety.

49 . (canceled)

50 . The composition for use in a method of diagnosis of claim 48 , wherein the detectable moiety comprises nanoparticles, such as metal-based nanoparticles or metal oxo-hydroxide nanoparticles.

51 . A process for producing amorphous magnesium-substituted calcium phosphate compositions that contain entrapped biologically active cargo material, the process comprising:
(a) providing a solution comprising calcium ions (Ca 2+ ), magnesium ions (Mg 2+ ) and a solution comprising phosphate ions (PO 4 2− ), wherein one or both of the solutions comprise one or more biologically active cargo materials; (b) mixing the solution comprising calcium ions (Ca 2+ ), magnesium ions (Mg 2+ ) with the solution comprising phosphate ions (PO 4 2− ) to precipitate amorphous magnesium-substituted calcium phosphate in which the biologically active cargo material is entrapped; (c) recovering the amorphous magnesium-substituted calcium phosphate; and (d) optionally washing and drying the amorphous magnesium-substituted calcium phosphate.

52 . (canceled)

53 . The process of claim 51 , wherein the biologically active cargo material increases the stability of the amorphous magnesium-substituted calcium phosphate to conversion to crystalline phases of calcium phosphate as compared to corresponding compositions that do not include entrapped cargo material.

53 - 54 . (canceled)

55 . (canceled)

56 . (canceled)
S 657 . (Cancelled)
37 - 58 . (Currently Amended) The process of claim 51 , further comprising formulating the amorphous magnesium-substituted calcium phosphate as a pharmaceutical composition.

Assignees

• Medical Res Council

Inventors

• Powell Jonathan Joseph
• Faria Nuno Jorge Rodriguez
• Pele Laetitia
• Hewitt Rachel
• Thomas-Mckay Emma

Classifications

• A61K9/1611

  Inorganic compounds · CPC title

• A61K9/5115

  Inorganic compounds · CPC title

• C01B25/32

  Phosphates of magnesium, calcium, strontium, or barium · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title