Nanoparticulate compositions

Patent metadata

Field	Value
Publication number	US-12539271-B2
Application number	US-202218286914-A
Country	US
Kind code	B2
Filing date	Apr 14, 2022
Priority date	Apr 15, 2021
Publication date	Feb 3, 2026
Grant date	Feb 3, 2026

Abstract

Suspensions containing oxidic nanoparticles as a dispersed phase and an aqueous solution containing citric acid as a diluent are disclosed. Advantageously, the oxidic nanoparticles contain bioglass and ceria. Also further disclosed are topical dosage forms including such oxidic nanoparticles and uses thereof. The dosage forms were found to be useful in the treatment of wounds and post-operative lesions, and particularly for the prevention of seroma, the prevention of infections and/or the prevention of inflammation.

First claim

The invention claimed is:

1 . A topical dosage form comprising a dispersed phase and a diluent, wherein the dispersed phase comprises a plurality of oxidic nanoparticles, the oxidic nanoparticles having an elemental composition, as measured by atomic emission spectroscopy (AES), comprising:
10-50 wt % Si, when calculated as SiO 2 , 0-30 wt % Ca and/or Sr, when calculated as CaO and/or SrO, 5-30 wt % Na, when calculated as Na 2 O, 0-10 wt % P, when calculated as P 2 O 5 , 0-10 wt % Zn, when calculated as ZnO, 10-90 wt % Ce, when calculated as CeO 2 , 0-10 wt % Ag when calculated as Ag, 0-50 wt % Zr; when calculated as ZrO 2 , and 0-90 wt % Mn, when calculated as MnO 2 ; wherein the oxidic nanoparticles have a hydrodynamic diameter of 10-2000 nm as measured by dynamic light scattering (DLS); wherein the oxidic nanoparticles comprise a first phase and a second phase, the first phase and the second phase being spatially separated, wherein
the first phase is an amorphous phase, predominantly containing oxides of Si, optionally Ca and/or SR, Na, P and Zn, as determined by powder X-Ray diffraction analysis (XRD); and
the second phase is a crystalline phase, predominantly containing Ceria and optionally Ag or Zr, as determined by powder XRD; and
wherein the diluent comprises:
water,
citric acid,
and optionally further pharmaceutically acceptable additives; and
wherein a ratio of the oxidic nanoparticles: citric acid is from 0.1 to 100 wt/wt.

2 . The topical dosage form of claim 1 , wherein the first phase and the second phase form nanoparticles selected from the group consisting of core-shell nanoparticles, janus nanoparticles, mixed phase nanoparticles, phase-segregated nanoparticles, and mixtures thereof.

3 . The topical dosage form of claim 1 , wherein the first phase is an amorphous phase, predominantly containing oxides of Si,
Ca and/or Sr, Na, P and Zn, as determined by powder XRD; and the second phase is a crystalline phase, predominantly containing Ceria and Ag, as determined by powder XRD.

4 . The topical dosage form according to claim 1 , wherein said first phase is a bioactive glass, comprising
(a-1) 20-60 wt % Silica, when calculated as SiO 2 , (a-2) 10-50 wt % Ca, but no Sr, when calculated as calcium oxide, (a-3) 5-50 wt % Na, when calculated as sodium oxide, and (a-4) 0-20 wt % P, when calculated as phosphorus oxide; or (b-1) 20-60 wt % Silica, when calculated as SiO 2 , (b-2) 10-50 wt % of a combination of Ca and Sr, when calculated as calcium oxide and strontium oxide, (b-3) 5-50 wt % Na, when calculated as sodium oxide, and (b-4) 0-20 wt % P, when calculated as phosphorus oxide; or (c-1) 20-60 wt % Silica, when calculated as SiO 2 , (c-2) strontium oxide, 10-50 wt %, but no calcium oxide, (c-3) 5-50 wt % Na, when calculated as sodium oxide, and (c-4) 0-20 wt % P, when calculated as phosphorus oxide; and wherein the first phase further optionally comprises a dopant selected from the group consisting of Ag, Cu, Ga, Co, Zn, and combinations thereof.

5 . The topical dosage form according to claim 1 , wherein said second phase is a ceria selected from compounds of formula (I)

wherein x is between 0 and 0.67; and
wherein up to 10 wt % of Ce may be replaced by a dopant selected from the group consisting of Zr, Zn, Cu, Ag, Ga, and combinations thereof.

6 . The topical dosage form according to claim 2 , wherein said oxidic nanoparticles comprise a mixture of mixed-phase nanoparticles and phase-segregated nanoparticles, and said oxidic nanoparticles have an elemental composition, as measured by AES:
15-25 wt % Si, when calculated as SiO 2 , 5-10 wt % Ca when calculated as CaO, 5-10 wt % Sr, when calculated as SrO, 10-15 wt % Na, when calculated as Na 2 O, 1.5-3 wt % P, when calculated as P 2 O 5 , 1-3 wt % Zn, when calculated as ZnO, and 45-55 wt % Ce, when calculated as CeO 2 .

7 . The topical dosage form according to claim 1 , wherein a combination of citric acid and its sodium salt are present at a molar ratio of 1:10 to 10:1 in the topical dosage form.

8 . The topical dosage form according to claim 1 , wherein the diluent comprises the pharmaceutically additives selected to obtain a physiological composition.

9 . The topical dosage form according to claim 1 , wherein the dosage form complies with one or more of the following (a)-(d):
(a) concentration of the oxidic nanoparticle in the topical dosage form is 0.01-100 mg/ml; (b) the pH is 4-9; (c) osmolality is 0-500 milli-osmoles/kg; and (d) viscosity is 0.2-10000 cP.

10 . A method of manufacturing the topical dosage form according to claim 1 , comprising a step of combining oxidic nanoparticles and a diluent, optionally with ultra-sonication,
wherein the oxidic nanoparticles having an elemental composition, as measured by Auger electron spectroscopy (AES), comprising: 10-50 wt % Si, when calculated as SiO 2 , 0-30 wt % Ca and/or Sr, when calculated as CaO and/or SrO, 5-30 wt % Na, when calculated as Na 2 O 0-10 wt % P, when calculated as P 2 O 5 , 0-10 wt % Zn, when calculated as ZnO, 10-90 wt % Ce, when calculated as CeO 2 , 0-10 wt % Ag when calculated as Ag, 0-50 wt % Zr; when calculated as ZrO 2 , and 0-90 wt % Mn, when calculated as MnO 2 ; wherein the oxidic nanoparticles have a hydrodynamic diameter of 10-2000 nm as measured by dynamic light scattering (DLS); wherein the oxidic nanoparticles comprise a first phase and a second phase, the first phase and the second phase being spatially separated, wherein the first phase is an amorphous phase predominantly containing oxides of Si, optionally Ca/Sr Ca and/or Sr, Na, P and Zn, as determined by powder X-Ray diffraction analysis (XRD); and the second phase is a crystalline phase, predominantly containing Ceria and optionally Ag or Zr, as determined by powder XRD, wherein the diluent comprises: water, citric acid, and optionally further pharmaceutically acceptable additives; and wherein a ratio of the oxidic nanoparticles: citric acid is between 0.1 to 100 wt/wt.

11 . The topical dosage form according to claim 1 , for use as a therapeutic agent and/or for use in surgery and/or for use as a first aid treatment.

12 . A method for therapeutic treatment of a defective soft tissue of a subject, comprising administering the topical dosage form according to claim 1 to the defective soft tissue.

13 . The method of claim 12 , wherein the defective soft tissue is a wound.

14 . The method of claim 12 , wherein the administration of the topical dosage form treats seroma.

15 . A method for treating therapeutic treatment of an infection and/or inflammation of a subject, comprising administering the topical dosage form of claim 1 to the subject.

16 . The method of claim 13 , wherein the wound comprises surgical wounds, accidental wounds, or a combination thereof.

Assignees

• Empa Eidgenoessische Mat & Forschungsanstalt
• Eth Zuerich

Inventors

• Matter Tino
• Herrmann Inge

Classifications

• B82Y5/00

  Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P17/02

  for treating wounds, ulcers, burns, scars, keloids, or the like · CPC title

• A61K33/42

  Phosphorus; Compounds thereof · CPC title

• A61K33/38

  Silver; Compounds thereof · CPC title