Low Viscosity Liquid Polymeric Delivery System

• US 20090181068A1
• Filed: 04/10/2008
• Published: 07/16/2009
• Est. Priority Date: 01/14/2008
• Status: Abandoned Application

• Current Assignee: Dunn Research & Consulting, LLC
• Original Assignee: Dunn Research & Consulting, LLC
• Inventors: Dunn, Richard L.
• Application Number:
  US12/100,562
• Publication Number:
  US 20090181068A1
• Time in Patent Office: Days
• US Class Current: 424/426
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 31/65 Tetracyclines
• CPC Class Codes: A61K 33/243 Platinum; Compounds thereof
• CPC Class Codes: A61K 9/0024 Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue compositions for intravenous administration, normal injectable solutions or dispersions for, e.g. subcutaneous administration A61K9/0019; brain implants A61K9/0085; (coated) prostheses, catheters or stents A61L
• CPC Class Codes: A61L 2300/406 Antibiotics
• CPC Class Codes: A61L 2300/416 Anti-neoplastic or anti-proliferative or anti-restenosis or anti-angiogenic agents, e.g. paclitaxel, sirolimus
• CPC Class Codes: A61L 2300/43 Hormones, e.g. dexamethasone
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 2400/06 Flowable or injectable implant compositions
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 29/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/14 Materials characterised by their function or physical properties , e.g. lubricating compositions
• CPC Class Codes: A61L 29/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/06 : obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/10 : Macromolecular materials
• CPC Class Codes: A61L 31/14 : Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 31/148 : Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 : Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 25/18 : Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: C08L 67/04 : Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence

Abstract

Low viscosity biodegradable polymer solutions of a liquid biodegradable polymer and biocompatible solvent and methods of using the compositions to form a liquid polymer implant are provided.

Claims

1. A liquid polymer composition, comprising:

a biodegradable liquid polymer; and

a biocompatible organic solvent;

wherein the composition, when placed in contact with an aqueous medium or body fluid remains in a liquid form and does not form a solid in situ.

2. The composition of claim 1, wherein the polymer is selected from the group consisting of polylactic acid, polyglycolic acid, polylactide, polyglycolide, polycaprolactones, polyanhydrides, polyamides, polyurethanes, polyesteramides, polyorthoesters, polydioxanones, polyacetals, polyketals, polycarbonates, polyphosphazenes, polyhydroxybutyrates, polyhydroxvalerates, polyalkylene oxalates, polyalkylene succinates, poly(malic acid), polyethylene glycol, hyaluronic acid, chitin, chitosan, and copolymers, terpolymers, and combinations or mixtures thereof.

3. The composition of claim 1, wherein the polymer is a copolymer or terpolymer of any combination of lactide, glycolide, caprolactone, p-dioxanone, trimethylene carbonate, 1,5-dioxepan-2-one, 1,4-dioxepan-2-one, ethylene oxide, propylene oxide, sebacic anhydride, diketene acetals/diols, and lactic acid.

4. The composition of claim 1, wherein the solvent is a hydrophilic organic solvent having a water solubility greater than 10% by weight of said solvent in water.

5. The composition of claim 4, wherein the organic solvent is selected from the group consisting of N-methyl-2-pyrrolidone, 2-pyrrolidone, N-ethyl-2-pyrrolidone, N-cyclohexyl-2-pyrrolidone, N-hydroethyl-2-pyrrolidone, dimethyl acetamide, dimethyl formamide, acetic acid, lactic acid, ethanol, propanol, methyl lactate, ethyl lactate, methyl acetate, diethylene glycol monomethyl ether, glycofurol, glycerol formal, isopropylidene glycerol, dimethyl sulfoxide, ε

-caprolactone, butyrolactone, propylene glycol, polyethylene glycol, glycerol, 1,3-butyleneglycol, methoxypolyethylene glycol, methoxypropylene glycol, acetone, methyl ethyl ketone, tetrahydrofuran, and combinations thereof.

6. The composition of claim 4, wherein the solvent is selected from the group consisting of N-methyl-2-pyrrolidone, 2-pyrrolidone, dimethyl acetamide, dimethyl sulfoxide, ethyl lactate, glycofurol, glycerol formal, isopropylidene glycerol, propylene glycol, polyethylene glycol, methoxypolyethylene glycol, methoxypropylene glycol, and combinations thereof.

7. The composition of claim 1, wherein the solvent is a lipophilic organic solvent having a water solubility less than 10% by weight of the solvent in water.

8. The composition of claim 7, wherein the solvent is selected from the group consisting of ethyl acetate, ethyl butyrate, ethyl oleate, isopropyl palmitate, ethyl palmitate, methyl palmitate, isopropyl myristate, diethyl malonate, diethyl succinate, dimethyl adipate, dimethyl succinate, dibutyl sebacate, triacetin, triethyl citrate, tributyrin, acetyl triethyl citrate, acetyl tributyl citrate, acetyl trihexyl citrate, butyryl trihexyl citrate, tributyl citrate, caprylic/capric triglycerides, caprylic/capric/linoleic triglyceride, caprylic/capric/succinic triglyceride, propylene glycol dicaprylate/caprate, benzyl alcohol, ethyl benzoate, benzyl benzoate, propylene carbonate, dimethyl carbonate, N,N-diethyl-toluamide, N-dodecyl-2-pyrrolidone, N-octyl-2-pyrrolidone, N-methyl-2-caprolactam, N-dodecyl-caprolactam, heptanoic acid, oleic acid, sesame oil, peanut oil, castor oil, and combinations thereof.

9. The composition of claim 7, wherein the solvent is selected from the group consisting of ethyl acetate, ethyl oleate, isopropyl myristate, triacetin, triethyl citrate, acetyl tributyl citrate, ethyl benzoate, benzyl benzoate, sesame oil, and combinations thereof.

10. The composition of claim 1, wherein the solvent is a combination of a hydrophilic solvent and a lipophilic solvent.

11. A composition, comprising:

a pharmaceutically acceptable, biodegradable liquid polymer; and

a biocompatible organic solvent that is dissolvable or dispersible in situ in a body fluid;

wherein the composition when placed in a body forms a polymeric material having a liquid consistency which does not form into a solid in situ.

12. The composition of claim 11, further comprising a therapeutically effective amount of a biologically active agent.

13. The composition of claim 12 wherein the biologically active agent is selected from the group consisting of cisplatin, carboplatin, anastozole, fulvestrant, exemestane, estradiol, testosterone, misoprostol, follicle-stimulating hormone, dustasteride, doxycycline, ciprofloxacin, quinolone, ivermectin, haloperidol, diazepam, risperidone, olanzapine, naltrexone, fentanyl, buprenorphine, butorphanol, loperamide, nafarelin, buserelin, histrelin, deslorelin, leuprolide, goserelin, triptorelin, ganirelix, abarelix, cetrorelix, teverelix, octreotide, lanreotide, human growth hormone, interferon-alpha, interferon-beta, interferon-gamma, interleukin, calcitonin, growth hormone releasing peptides, glucagon-like peptides, granulocyte-colony stimulating factor, nerve growth factor, platelet-derived growth factor, insulin-like growth factor, vascular endothelial growth factor, fibroblast growth factor, bone morphogenic protein, erythropoietin, and salts, complexes, prodrugs, and analogs thereof.

14. The composition of claim 11, wherein the polymer is a liquid at 25°

C. up to 37°

C.

30. The composition of claim 12, wherein the biologically active agent is released from the polymeric material as the polymeric material biodegrades.

15-23. -23. (canceled)

24. A kit comprising in association:

a container of a pharmaceutically acceptable, biodegradable liquid polymer; and

a container of a biocompatible organic solvent that is dissolvable or dispersible in situ in a body fluid;

wherein the liquid polymer and the organic solvent when combined, will form a liquid composition which, when placed in contact with a body fluid, will form a polymeric implant having a liquid consistency which does not form into a solid in situ; and

directions for preparation and administration of the liquid composition to form the polymeric implant.

25. The kit of claim 24, further comprising a container of a therapeutically effective amount of a biologically active agent;

wherein the biologically active agent, when combined in the liquid composition and placed in contact with the body fluid will be released into the body as the polymeric implant biodegrades within the body.

26. The kit of claim 24, further comprising a container of a therapeutically effective amount of a biologically active agent in a pharmaceutically acceptable carrier or diluent;

wherein the biologically active agent, when combined in the liquid composition and placed in contact with body fluid will be released into the body as the polymeric implant biodegrades within the body.

27. A kit comprising in association:

a container of a liquid composition comprising a pharmaceutically acceptable, biodegradable liquid polymer dissolved in a biocompatible organic solvent that is dissolvable or dispersible in situ in a body fluid;

wherein the liquid composition, when placed in contact with body fluid, will form a polymeric implant having a liquid consistency which does not form into a solid in situ; and

directions for administration of the liquid composition to form the polymeric implant.

28. The kit of claim 27, further comprising a container of a therapeutically effective amount of a biologically active agent;

wherein the biologically active agent, when combined in the liquid composition and placed in contact with body fluid will be released as the polymeric implant biodegrades within the body.

29. A kit comprising in association:

a container of a liquid composition comprising a pharmaceutically acceptable, biodegradable liquid polymer dissolved in a biocompatible organic solvent that is dissolvable or dispersible in situ in a body fluid, and a biologically active agent;

wherein the liquid composition, when placed in contact with body fluid, will form a polymeric implant having a liquid consistency which does not form into a solid in situ; and

the biologically active agent will be released into the body as the polymeric implant biodegrades within the body; and

directions for administration of the liquid composition to form the polymeric implant.