Drug-delivery systems

Patent metadata

Field	Value
Publication number	US-9480654-B2
Application number	US-201213648846-A
Country	US
Kind code	B2
Filing date	Oct 10, 2012
Priority date	Oct 25, 2005
Publication date	Nov 1, 2016
Grant date	Nov 1, 2016

Abstract

The invention relates to novel particulate drug-delivery systems based on a polymer support containing at least one linear, branched or cross-linked polymer in a fraction of over 50 percent by weight in relation to the total weight of the support. The system is characterized in that at least one signal substance for transport through a biological barrier and at least one active ingredient are stored, the support, signal substance and active ingredient having no covalent links and no active-ingredient specific and signal substance specific coordinative links between one another.

First claim

The invention claimed is:

1. A particulate drug delivery system, comprising:
a polymeric carrier,
at least one signal substance for transport through a biological barrier comprising at least one peptide derived from a lactoferrin protein which consists of SEQ ID No. 3, SEQ ID No. 4, SEQ ID No. 29, or SEQ ID No. 30, and
at least one active ingredient,
wherein the polymeric carrier, signal substance and active ingredient have no covalent linkages with one another.

2. The particulate drug delivery system of claim 1 , wherein both the signal substance and the active ingredient are present dispersed or coacervated in the polymeric carrier.

3. The particulate drug delivery system of claim 1 , wherein the polymeric carrier comprises at least one branched or crosslinked polymer with a proportion of more than 50% by weight based on the total weight of the carrier.

4. The particulate drug delivery system of claim 1 , wherein the polymeric carrier is a dendritic polymer.

5. The particulate drug delivery system of claim 1 , wherein the polymeric carrier is a branched hydrogel or a comb polymer.

6. The particulate drug delivery system of claim 1 , wherein the polymeric carrier is a dendritic polymer having a molar mass above 1000 g/mol and/or a melt viscosity of less than 3.0 Pas at 80° C.

7. The particulate drug delivery system of claim 1 , wherein the polymeric carrier is at least one of
a dendritic polymer selected from the group consisting of polyamidoamine dendrimers, of polypropyleneimine dendrimers, of polyethylene oxide-based dendrimers, of polyether dendrimers, of polyamido dendrimers, of polylysine dendrimers, of polyaryl ether dendrimers,
a dendritic polymer selected from the group consisting of polyesters, polyesteramides, polyethers, polyamides, polyethyleneimines; polycaprolactones, polyglycerols, polyglycolides, polylactides, polylactide-co-glycolides, polytartrates and polysaccharides, or
a branched or crosslinked carrier polymer selected from the group consisting of natural and artificial carbohydrate homo- or copolymers, of natural and artificial amino acid polymers, of natural and artificial nucleic acids, of polyamines, of polyimines, of polyesters, of polyethers, of polyols, of polyolefins, of polyalkylene glycols, of polyamides, of polyacetals, of polyacrylates, of polyacetates, of polyurethanes, of organosilicon polymers, of epoxy resins, of polythiols, of polycarbonates, of polycaprolactones, of polyglycolides, of polylactides, of polylactide-co-glycolides and of polytartrates.

8. The particulate drug delivery system of claim 1 , wherein the active ingredient is an unmodified active pharmaceutical ingredient.

9. The particulate drug delivery system of claim 1 , wherein the active ingredient and/or signal substance are non-specifically aggregated in different layers in the drug delivery particles.

10. The particulate drug delivery system of claim 1 , wherein there is non-specific aggregation of the active ingredient in an inner layer and of the signal substance in a subsequent layer in the particulate drug delivery system.

11. The particulate drug delivery system of claim 1 , which comprises at least one active ingredient selected from the group consisting of antibodies, peptide hormones, receptors or peptidic ligands thereof, enzymes, interferons, tumor necrosis factor, cachectin, dihydrofolate reductase, lymphotoxin, interleukins, tumor suppressor proteins, plasmin, urokinase, hirudin, streptokinase, urokinase, tissue plasminogen activator, protein C, protein S, phospholipase A 2 , uromodulin, Tamm-Horsfall protein, insulin, trypsin inhibitor, lysozyme, thymopoietin, peptide antibiotics, erythropoietin, hepatotherapeutic substances, neuroprotective substances, immunotherapeutics, immunosuppressants, low molecular weight active ingredients for cardiovascular disorders or cancer, analgesics, low molecular weight antiinflammatory, antibiotic antimicrobial active ingredients, low molecular weight hormones, nucleic acid fragments, nucleic acids, nucleoside analogs, β-interferons, α-lipoic acid, peptide analogs, enzyme or receptor inhibitors, enzyme or receptor agonists, enzyme or receptor antagonists, prostaglandins, steroids, cytostatics, heterocyclic antibiotics and prodrugs thereof.

12. The particulate drug delivery system of claim 1 , wherein the active ingredient is α-Iipoic acid.

13. The particulate drug delivery system of claim 1 , wherein the polymeric carrier is a polylactide-co-glycolide.

14. The particulate drug delivery system of claim 1 , wherein the signal substance consists of SEQ ID NO:3.

15. The particulate drug delivery system of claim 1 , wherein the signal substance consists of SEQ ID NO:4.

16. The particulate drug delivery system of claim 1 , wherein the signal substance consists of SEQ ID NO:29.

17. The particulate drug delivery system of claim 1 , wherein the signal substance consists of SEQ ID NO:30.

18. A method of producing the particulate drug delivery system of claim 1 , comprising combining the polymeric carrier, signal substance and active ingredient into a particulate form.

Assignees

• Evonik Roehm Gmbh

Inventors

• Seiler Matthias
• Windhab Norbert
• Stickler Manfred
• Petereit Hans-Ulrich

Classifications

• A61K9/146 Primary

  with organic macromolecular compounds · CPC title

• A61K47/62

  the modifying agent being a protein, peptide or polyamino acid · CPC title

• A61K47/59

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes · CPC title

• A61K47/595

  Polyamides, e.g. nylon (polyamino acids A61K47/62) · CPC title

• A61K9/1641 Primary

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers · CPC title