SOLID NANOPARTICLE WITH INORGANIC COATING

• US 20180085321A1
• Filed: 07/10/2017
• Published: 03/29/2018
• Est. Priority Date: 05/24/2013
• Status: Active Grant

• Current Assignee: Nanexa AB
• Original Assignee: Nanexa AB
• Inventors: CARLSSON, Jan-Otto, JOHANSSON, Anders, ROOTH, Marten
• Granted Patent: US 10,478,402 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/167 having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
• CPC Class Codes: A61K 31/4422 1,4-Dihydropyridines, e.g. nifedipine, nicardipine
• CPC Class Codes: A61K 9/143 with inorganic compounds
• CPC Class Codes: A61K 9/145 with organic compounds
• CPC Class Codes: A61K 9/5073 having two or more different coatings optionally including drug-containing subcoatings
• CPC Class Codes: A61K 9/5115 Inorganic compounds
• CPC Class Codes: A61K 9/5192 Processes
• CPC Class Codes: C23C 16/403 of aluminium, magnesium or beryllium
• CPC Class Codes: C23C 16/405 of refractory metals or yttrium
• CPC Class Codes: C23C 16/4417 Methods specially adapted for coating powder
• CPC Class Codes: C23C 16/442 using fluidised bed process
• CPC Class Codes: C23C 16/45555 applied in non-semiconductor technology

Abstract

A nanoparticle having a solid core comprising a biologically active substance, said core being enclosed by an inorganic coating, a method for preparing the nanoparticle, and the use of the nanoparticle in therapy. A kit comprising the nanoparticle and a pharmaceutical composition comprising the nanoparticle.

Claims

1-23. -23. (canceled)

24. A method of preparing a plurality of coated particles of a size that is between 1 nm and 50 μ

m, said coated particles having a solid core comprising a biologically active substance, said solid core being enclosed by an inorganic coating;

the method comprising

applying more than one layer of inorganic material comprising at least one metal or metalloid element to a plurality of said solid cores by an application method selected from atomic layer deposition, chemical vapour deposition or physical vapour deposition, wherein the inorganic material and/or precursors for forming the inorganic material is/are present in gas phase, and

submitting said solid cores to intermittent agitation between application of layers of inorganic material so as to obtain either;

(a) disaggregation of particle aggregates formed during application of a coating, or

(b) a spatial rearrangement of particles.

25. The method of claim 24, comprising

(i) applying inorganic material to a plurality of said solid cores

(ii) submitting the plurality of said solid cores to agitation,

(iii) repeating step (i) n times, wherein n is an integer of at least 1, and

(iv) when n is an integer of at least 2, repeating step (ii) after at least some of the steps (i).

26. The method of claim 25, wherein n is an integer of at least 1 and at most 50.

27. The method of claim 26, wherein n is an integer of at least 2 and at most 20.

28. The method of claim 27, wherein n is an integer of at least 3 and at most 10.

29. The method of claim 24, wherein the element that is a metal or metalloid is present as an oxide, a hydroxyoxide, a carbide, a selenide, a nitride, sulphide, fluoride, chloride and/or a salt.

30. The method of claim 24, wherein the element is present as an oxide.

31. The method of claim 24, wherein the inorganic material comprises aluminium oxide (Al₂O₃), titanium dioxide (TiO₂), iron oxide (Fe_xO_y), gallium oxide (Ga₂O₃) and magnesium oxide (MgO), zinc oxide (ZnO), niobium oxide (Nb₂O₅), hafnium oxide (HfO₂), tantalum oxide (Ta₂O₅), lanthanum oxide (La₂O₃), zirconium dioxide (ZrO₂) and/or silicon dioxide (SiO₂).

32. The method of claim 24, wherein the inorganic coating comprises aluminium oxide, titanium dioxide and/or zinc oxide.

33. The method of claim 24, wherein several layers of inorganic material are applied to the solid core.

34. The method of claim 24, wherein the biologically active substance is a therapeutically active substance.

35. The method of claim 24, wherein the solid core essentially comprises the biologically active agent.

36. The method of claim 24, wherein the inorganic coating surrounds, encloses or encapsulates the biologically active agent sufficiently completely to enable a therapeutically effective controlled or delayed release of said biologically active agent therefrom.

37. The method of claim 24, wherein the inorganic coating is of an essentially uniform thickness that is in the range between 0.1 and 500 nm.

38. The method of claim 37, wherein the thickness is in the range between 0.1 and 100 nm.

39. The method of claim 37, wherein the thickness is in the range between 0.1 and 50 nm.

40. The method of claim 24, wherein the biologically active substance is selected from the group:

an analgesic, an anesthetic, an anti-inflammatory agent, an anthelmintic, an anti-arrhythmic agent, an antiasthma agent, an antibiotic, an anticancer agent, an anticoagulant, an antidepressant, an antidiabetic agent, an antiepileptic, an antihistamine, an antitussive, an antihypertensive agent, an antimuscarinic agent, an antimycobacterial agent, an antineoplastic agent, an antioxidant agent, an antipyretic, an immunosuppressant, an immunostimulant, an antithyroid agent, an antiviral agent, an anxiolytic sedative, a hypnotic, a neuroleptic, an astringent, a bacteriostatic agent, a beta-adrenoceptor blocking agent, a blood product, a blood substitute, a bronchodilator, a buffering agent, a cardiac inotropic agent, a chemotherapeutic, a contrast media, a corticosteroid, a cough suppressant, an expectorant, a mucolytic, a diagnostic agent, a diagnostic imaging agent, a diuretic, a dopaminergic, an antiparkinsonian agent, a free radical scavenging agent, a growth factor, a haemostatic, an immunological agent, a lipid regulating agent, a muscle relaxant, a protein, a peptide, a polypeptide, a parasympathomimetic, a parathyroid calcitonin, a biphosphonate, a prostaglandin, a radio-pharmaceutical, a hormone, a sex hormone, an anti-allergic agent, an appetite stimulant, an anoretic, a steroid, a sympathomimetic, a thyroid agent, a vaccine, a vasodilator and a xanthine.

41. The method of claim 24, wherein the biologically active substance is selected from the group:

alprazolam, amiodarone, amlodipine, astemizole, atenolol, azathioprine, azelatine, beclomethasone, budesonide, buprenorphine, butalbital, carbamazepine, carbidopa, cefotaxime, cephalexin, cholestyramine, ciprofloxacin, cisapride, cisplatin, clarithromycin, clonazepam, clozapine, cyclosporin, diazepam, diclofenac sodium, digoxin, dipyridamole, divalproex, dobutamine, doxazosin, enalapril, estradiol, etodolac, etoposide, famotidine, felodipine, fentanyl citrate, fexofenadine, finasteride, fluconazole, flunisolide, flurbiprofen, fluvoxamine, furosemide, glipizide, gliburide, ibuprofen, isosorbide dinitrate, isotretinoin, isradipine, itraconazole, ketoconazole, ketoprofen, lamotrigine, lansoprazole, loperamide, loratadine, lorazepam, lovastatin, medroxyprogesterone, mefenamic acid, methylprednisolone, midazolam, mometasone, nabumetone, naproxen, nicergoline, nifedipine, norfloxacin, omeprazole, paclitaxel, phenyloin, piroxicam, quinapril, ramipril, risperidone, sertraline, simvastatin, sulindac, terbinafine, terfenadine, triamcinolone, valproic acid, zolpidem and pharmaceutically acceptable salts of any of these agents.

42. The method of claim 24, wherein one or more intermediary layers comprising one or more surfactants is/are present.

43. The method of claim 24, wherein the outer surface of the inorganic coating is derivatized or functionalized by attachment of one or more chemical moieties to the outer surface of the coating.

44. The method of claim 43, wherein the one or more chemical moieties comprises one or more compounds that enhances the targeted delivery of the nanoparticles in the body of a subject to whom the formulation are administered.

45. The method of claim 43, wherein the one or more chemical moieties comprise an anchoring group or “

handle”

which contains a silane function to which a targeting molecule may be attached.

46. The method of claim 45, wherein the one or more chemical moieties comprises one or more nucleic acids, antibodies, antibody fragments, receptor-binding proteins or receptor-binding peptides.

47. A plurality of coated nanoparticles obtainable by a method according to claim 24.

48. The plurality of coated nanoparticles according to claim 47, wherein the biologically active substance is a therapeutically active substance.

49. A pharmaceutical composition comprising a plurality of coated nanoparticles according to claim 47 and a pharmaceutically acceptable carrier.

50. A pharmaceutical composition according to claim 49 in the form of a sterile injectable or infusible suspension of particles in a parenterally-acceptable diluent

51. A pharmaceutical composition according to claim 50, which is in the form of a sterile aqueous or oleaginous suspension.

52. A method of treatment of a medical disorder, which method comprises administering to a patient suffering from or susceptible to said medical disorder a pharmaceutical formulation according to claim 49, wherein the biologically active agent is effective in the treatment of said medical disorder.