Polyesteramide platform for site specific drug delivery

Patent metadata

Field	Value
Publication number	US-9603943-B2
Application number	US-201514750732-A
Country	US
Kind code	B2
Filing date	Jun 25, 2015
Priority date	Apr 17, 2006
Publication date	Mar 28, 2017
Grant date	Mar 28, 2017

Abstract

A therapeutic agent delivery system formed of a specific type of poly(ester amide) (PEA), a therapeutic agent, and a water miscible solvent is described herein. A method of delivering the therapeutic agent delivery system by delivering the therapeutic agent delivery system formed of a PEA polymer, a therapeutic agent, and a water miscible solvent to a physiological environment and separating the phase of the therapeutic agent delivery system to form a membrane from the polymer to contain the therapeutic agent within the physiological environment is also described. Additionally disclosed is a kit including a syringe and a therapeutic agent delivery system within the syringe.

First claim

The invention claimed is:

1. A composition comprising:
a first polymer cross-linked with a second polymer, the second polymer being different than the first polymer, wherein the first polymer comprises a poly (ester amide) polymer comprising an amino acid, and the second polymer comprises a biodegradable polymer;
a therapeutic agent; and
a solvent, wherein the first polymer cross-linked with the second polymer and the solvent are combined to form a heterogeneous mixture in liquid form and the solvent is at least partially water miscible such that the solvent diffuses out of the heterogeneous mixture in vivo, and wherein the average molecular weight of the first polymer is from 10,000 Daltons to 200,000 Daltons.

2. The composition of claim 1 , wherein
the solvent is selected from the group consisting of ethanol, propylene glycol, benzyl benzoate, benzyl alcohol, n-methylpyrrolidone (NMP) and dimethyl sulfoxide (DMSO).

3. The composition of claim 1 wherein the amino acid is selected from the group consisting of lysine, tyrosine, glutamic acid and cysteine.

4. The composition of claim 1 wherein the amino acid is a first amino acid, the composition further comprising a second amino acid, wherein at least one of the first amino acid or the second amino acid is lysine.

5. The composition of claim 4 wherein both the first amino acid and the second amino acid are lysine.

6. The composition of claim 1 wherein the amino acid is a first amino acid, the composition further comprising a second amino acid, wherein at least one of the first amino acid or the second amino acid is selected from the group consisting of glycine, valine, alanine, leucine, isoleucine, phenylalanine.

7. The composition of claim 1 wherein the second polymer is one of poly(butyl methacrylate), poly(ethyl methacrylate), poly(ethyl methacrylate-co-butyl methacrylate), poly(vinylidene fluoride), poly(vinylidene fluoride-co-hexafluoro propene), poly(N-vinyl pyrrolidone), poly(hydroxyvalerate), poly(L-lactic acid), polycaprolactone, poly(lactide-co-glycolide), poly(hydroxybutyrate), poly(hydroxybutyrate-co-valerate), polydioxanone, polyorthoester, polyanhydride, poly(glycolic acid), poly(D,L-lactic acid), poly(glycolic acid-co-trimethylene carbonate), polyphosphoester, polyphosphoester urethane, poly(amino acid), cyanoacrylate, poly(trimethylene carbonate), poly(iminocarbonate), co-poly (ether-ester), polyalkylene oxalate, and polyphosphazene.

8. The composition of claim 1 wherein the second polymer is a biomolecule selected from one of fibrin, fibrinogen, cellulose, starch, collagen and hyaluronic acid.

9. The composition of claim 1 wherein the second polymer is one of polyurethane, silicone, polyester, polyolefin, polyisobutylene, ethylene-alphaolefin copolymer, polyvinyl chloride, polyvinyl methyl ether, polyvinylidene chloride, polyacrylonitrile, polyvinyl ketones, polystyrene, polyvinyl acetate, poly(ethylene-co-vinyl alcohol) (EVAL), ethylene-methyl methacrylate copolymer, acrylonitrile-styrene copolymer, ABS resin, ethylene-vinyl acetate copolymer, Nylon 66, polycaprolactam, alkyd resin, polycarbonate, polyoxymethylene, polyimide, polyether, epoxy resin, rayon, rayon-triacetate, cellulose, cellulose acetate, cellulose butyrate, cellulose acetate butyrate, cellophane, cellulose nitrate, cellulose propionate, cellulose ether, and carboxymethyl cellulose.

10. A composition comprising:
a first polymer cross-linked with a second polymer, wherein the first polymer is a poly (ester amide) polymer comprising the reaction product of a diacid, a diol, a triol, a first diol, and a second diol or diamine, and the second polymer is a biodegradable polymer;
a therapeutic agent; and
a solvent, wherein the first polymer cross-linked with the second polymer and the solvent are combined to form a heterogeneous mixture in liquid form and the solvent is at least partially water miscible such that the solvent diffuses out of the heterogeneous mixture in vivo.

11. The composition of claim 10 wherein the diacid of the poly (ester amide) polymer has between two and twelve carbons and comprises one of an aliphatic diacid and an unsaturated diacid.

12. The composition of claim 10 wherein the diol of the poly (ester amide) polymer comprises between two and twelve carbons and comprises one of a branched diol and an unsaturated diol.

13. The composition of claim 10 wherein the second diol or diamine is within a backbone of the poly (ester amide) polymer.

14. A composition comprising:
a first polymer cross-linked with a second polymer, wherein the first polymer is a poly (ester amide) polymer comprising the reaction product of an amino acid, a diamine and a hydroxyacid, and the second polymer is a biodegradable polymer;
a therapeutic agent; and
a solvent, wherein the first polymer cross-linked with the second polymer and the solvent are combined to form a heterogeneous mixture in liquid form and the solvent is at least partially water miscible such that the solvent diffuses out of the heterogeneous mixture in vivo.

15. The composition of claim 14 wherein the diamine is one of putrescine or cadaverene.

16. The composition of claim 1 , wherein the therapeutic agent is connected to the poly (ester amide) polymer as a pendant group or an in-chain group.

17. The composition of claim 1 , wherein the therapeutic agent is a polymeric agent.

18. The composition of claim 1 wherein the therapeutic agent has a low molecular weight in the approximate range of 100 grams per mole to 200,000 grams per mole.

19. The composition of claim 1 wherein the therapeutic agent is at least one of a pharmaceutical agent, a biologic, or an image-enhancing agent.

20. The composition of claim 19 wherein the biologic is one of a cell, a protein, a peptide, a monoclonal antibody, an amino acid, or a polyoligonucleotide.

21. The composition of claim 19 wherein the pharmaceutical agent is one of an anti-inflammatory, an anti-platelet, an anti-coagulant, an anti-fibrin, an anti-thrombotic, an anti-mitotic, an anti-biotic, an anti-allergic, an anti-oxidant, an anti-proliferative, or an anti-migratory.

22. The composition of claim 19 wherein the image-enhancing agent is one of a radiopaque dye or a magnetic resonance imaging agent.

23. The composition of claim 19 wherein the pharmaceutical agent comprises Sirolimus, Everolimus, ABT-578, or Paclitaxel.

24. The composition of claim 1 wherein the therapeutic agent is one of actinomycin D, actinomycin IV, actinomycin I1, actinomycin X1, actinomycin C1, dactinomycin, paclitaxel, docetaxel, methotrexate, azathioprine, vincristine, vinblastine, fluorouracil, doxorubicin hydrochloride mitomycin, sodium heparin, low molecular weight heparins, heparinoids, hirudin, argatroban, forskolin, vapiprost, prostacyclin, prostacyclin analogues, dextran, D-phe-pro-arg-chloromethylketone, dipyridamole, glycoprotein IIb/IIIa platelet membrane receptor antagonist antibody, recombinant hirudin, thrombin inhibitors, angiopeptin, angiotensin converting enzyme inhibitors, cilazapril, lisinopril, nifedipine, colchicines, fibroblast growth factor antagonists, fish oil, omega 3-fatty acid, histamine antagonists, lovastatin, antibodies specific for Platelet-Derived Growth Factor (PDGF) receptors, nitroprusside, phosphodiesterase inhibitors, prostaglandin inhibitors, suramin, serotonin blockers, steroids, thioprotease inhibitors, triazolopyrimidine, nitric oxide, pemirolast potassium, free radical scavengers

Assignees

• Abbott Cardiovascular Systems Inc

Inventors

• Kleiner Lothar W
• Hossainy Syed
• Pacetti Stephen
• Desnoyer Jessica

Classifications

• C08L77/12

  Polyester-amides · CPC title

• A61K31/4745

  condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48) · CPC title

• A61K47/48207 Primary

  Human Necessities · mapped topic

• A61K47/34

  Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence) · CPC title

• A61K31/727 Primary

  Heparin; Heparan · CPC title