Nanosystems for controlled transport of active molecules for diagnostic, prognostic and therapeutic purposes

Patent metadata

Field	Value
Publication number	US-2018360990-A1
Application number	US-201616061220-A
Country	US
Kind code	A1
Filing date	Dec 20, 2016
Priority date	Dec 21, 2015
Publication date	Dec 20, 2018
Grant date	—

Abstract

Disclosed is a nanoparticle system consisting of a polymer support or substrate in the form of nanoparticles to which a hydrolase enzyme able to degrade hyaluronic acid and one or more biologically and/or pharmacologically active molecules are covalently bonded, its preparation process and its uses in the diagnostic, prognostic and therapeutic fields.

First claim

1 . Nanoparticle system comprising polymeric nanoparticles consisting of a natural, synthetic or semisynthetic polymer or copolymer, bonded to a heterocarbon chain by covalent bonds between the functional groups present on the polymer or copolymer and the functional groups present on said heterocarbon chain, a hyaluronidase and one or more active molecules covalently bonded to said heterocarbon chain.

2 . Nanoparticle system as claimed in claim 1 wherein the synthetic or natural polymers or copolymers are selected from polystyrene, polylactic acid, polylactic coglycolic acid, poly(N-vinylpyrrolidone), polyethylene glycol, polycaprolactone, polyacrylic acid, polymethyl methacrylate, polyacrylamide, chitosan, gelatin, sodium alginate and albumin, preferably polystyrene.

3 . Nanoparticle system according to claim 1 wherein the functional groups present on the polymer are selected from primary or tertiary amines, epoxides and carboxyls, preferably primary or tertiary amines.

4 . Nanoparticle system according to claim 1 wherein the nanoparticles have a size ranging from 50 nm to 2000 nm, preferably from 100 to 500 nm, most preferably of 200 nm.

5 . Nanoparticle system according to claim 1 wherein the hyaluronidase enzyme is of human, animal, vertebrate, bacterial or recombinant origin, preferably recombinant.

6 . Nanoparticle system according to claim 1 wherein the heterocarbon chain is selected from saturated carbon chains with 6 to 24 carbons, methoxypolyethylene glycol chains, dimethylsuberimidate chains, polyethylene glycol chains, preferably N-Fmoc-N-succinyl-4,7,10-trioxa-1,13-tridecanediamine (PEG spacer).

7 . Nanoparticle system according to claim 1 wherein the functional groups of the heterocarbon chain are selected from glutaraldehyde, maleimide, active esters, disulphide groups, squaric acid and derivatives thereof.

8 . Nanoparticle system according to claim 1 , wherein the active molecules are of natural, semisynthetic, synthetic or recombinant origin.

9 . Nanoparticle system according to claim 7 wherein the active molecules are selected from medicaments, diagnostic agents, radioactive agents, antibodies, enzymes, proteins, peptides, hormones, growth factors, coagulation factors, cytokines, dyes, fluorophores, antibodies, nucleic acids, polynucleotides, sense and antisense oligonucleotides, molecular conjugates containing RNA or DNA, soluble RNA, DNA vectors, and natural, synthetic or recombinant vaccines.

10 . Nanoparticle system according to claim 8 wherein the enzymes are selected from human superoxide dismutase (hMnSOD) and native and/or modified bacterial collagenase.

11 . Pharmaceutical compositions comprising the nanoparticle systems of claim 1 in admixture with pharmaceutically acceptable excipients.

12 . Pharmaceutical compositions according to claim 10 in lyophilized form for reconstitution, or in aqueous suspension or gel form.

13 . Pharmaceutical compositions according to claim 11 for the subcutaneous, intradermal, intrathecal, intramuscular, intraperitoneal, intravenous, intra-arterial, transdermal, transcutaneous, transmucosal and inhalatory administration, preferably by subcutaneous, intradermal, transcutaneous, transdermal, transmucosal or intramuscular administration or by inhalation.

14 . Nanoparticle system according to claim 2 wherein the functional groups present on the polymer are selected from primary or tertiary amines, epoxides and carboxyls, preferably primary or tertiary amines.

15 . Nanoparticle system according to claim 2 wherein the nanoparticles have a size ranging from 50 nm to 2000 nm, preferably from 100 to 500 nm, most preferably of 200 nm.

16 . Nanoparticle system according to claim 3 wherein the nanoparticles have a size ranging from 50 nm to 2000 nm, preferably from 100 to 500 nm, most preferably of 200 nm.

17 . Pharmaceutical compositions comprising the nanoparticle systems of claim 2 in admixture with pharmaceutically acceptable excipients.

18 . Pharmaceutical compositions comprising the nanoparticle systems of claim 3 in admixture with pharmaceutically acceptable excipients.

19 . Pharmaceutical compositions comprising the nanoparticle systems of claim 4 in admixture with pharmaceutically acceptable excipients.

20 . Pharmaceutical compositions comprising the nanoparticle systems of claim 5 in admixture with pharmaceutically acceptable excipients.

Assignees

• Fidia Farm Spa
• Nanogetic S L

Inventors

• Sanchez Martin Rosario Maria
• Pernagallo Salvatore
• Unciti Broceta Juan Diego
• Messina Luciano
• Vaccaro Susanna
• Pilotto Laura

Classifications

• A61K47/6939

  the polymer being a polysaccharide, e.g. starch, chitosan, chitin, cellulose or pectin · CPC title

• A61K9/19

  lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} · CPC title

• A61K47/6937 Primary

  the polymer being PLGA, PLA or polyglycolic acid · CPC title

• A61K9/0073

  Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy; (nasal sprays A61K9/0043; inhalation of vapours of volatile or heated drugs, e.g. essential oils or nicotine, A61K9/007; devices A61M) · CPC title

• A61K38/446

  Superoxide dismutase (1.15) · CPC title