LOW BURST SUSTAINED RELEASE LIPOPHILIC AND BIOLOGIC AGENT COMPOSITIONS

• US 20150087671A1
• Filed: 05/16/2013
• Published: 03/26/2015
• Est. Priority Date: 05/16/2012
• Status: Abandoned Application

• Current Assignee: Micell Technologies Inc.
• Original Assignee: Micell Technologies Inc.
• Inventors: McClain, James B., Taylor, Charles Douglas, Carlyle, Wenda C.
• Application Number:
  US14/401,496
• Publication Number:
  US 20150087671A1
• Time in Patent Office: Days
• US Class Current: 514/291
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• 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: A61K 9/06 Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels composition of ointments, creams or gels A61K47/00
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• 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 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence

Abstract

A drug delivery composition including a lipophilic agent or a biologic agent and a polymer wherein the lipophilic agent exhibits sustained release and wherein there is less than 35% agent release within the first hour of elution. A drug delivery composition including a lipophilic agent or a biologic agent and a polymer wherein the elution profile is substantially linear, and wherein there is less than 35% agent release within the first hour of elution. The lipophilic agent may be crystalline and the biologic agent may be in active form.

Claims

1. A drug delivery composition comprising a lipophilic agent and a polymer, wherein said composition is a hydrogel, wherein the lipophilic agent exhibits sustained release, and wherein there is less than 35% lipophilic agent release within the first hour of elution.

3. The drug delivery composition of claim 1, or claim 2, wherein the elution profile is determined through in-vitro testing.

4. The composition of claim 1 or claim 2, wherein sustained release comprises the lipophilic agent releasing over a period of >

24 hours, >

3 days, >

1 week, >

10 days, or 16 days.

5. The drug delivery composition of claim 1, or claim 2, wherein there is less than 10% agent release within the first hour of elution.

7. The drug delivery composition of claim 1, or claim 2, wherein the lipophilic agent comprises a limus drug, mTOR inhibitors, antibiotic agents, and/or immunosuppressive agents.

8. The drug delivery composition of claim 7, wherein the lipophilic agent comprises a limus drug selected from rapamycin, biolimus (biolimus A9), 40-O-(2-Hydroxyethyl)rapamycin (everolimus), 40-O-Benzyl-rapamycin, 40-O-(4′

-Hydroxymethyl)benzyl-rapamycin, 40-O-[4′

-(1,2-Dihydroxyethyl)]benzyl-rapamycin, 40-O-Allyl-rapamycin, 40-O-[3′

-(2,2-Dimethyl-1,3-dioxolan-4(S)-yl)-prop-2′

-en-1′

-yl]-rapamycin, (2′

;

E,4′

S)-40-O-(4′

,5′

-Dihydroxypent-2′

-en-1′

-yl)-rapamycin, 40-O-(2-Hydroxy)ethoxycar-bonylmethyl-rapamycin, 40-O-(3-Hydroxy)propyl-rapamycin, 40-O-(6-Hydroxy)hexyl-rapamycin, 40-O-[2-(2-Hydroxy)ethoxy]ethyl-rapamycin 40-O-[(3S)-2,2-Dimethyldioxolan-3-yl]methyl-rapamycin, 40-O-[(2S)-2,3-Dihydroxyprop-1-yl]-rapamycin, 40-O-(2-Acetoxy)ethyl-rapamycin 40-O-(2-Nicotinoyloxy)ethyl-rapamycin, 40-O-[2-(N-Morpholino)acetoxy]ethyl-rapamycin, 40-O-(2-N-Imidazolylacetoxy)ethyl-rapamycin, 40-O-[2-(N-Methyl-N′

-piperazinyl)acetoxy]ethyl-rapamycin, 39-O-Desmethyl-39,40-O,O-ethylene-rapamycin, (26R)-26-Dihydro-40-O-(2-hydroxy)ethyl-rapamycin, 28-O-Methyl-rapamycin, 40-O-(2-Aminoethyl)-rapamycin, 40-O-(2-Acetaminoethyl)-rapamycin, 40-O-(2-Nicotinamidoethyl)-rapamycin, 40-O-(2-(N-Methyl-imidazo-2′

-ylcarbethoxamido)ethyl)-rapamycin, 40-O-(2-Ethoxycarbonylaminoethyl)-rapamycin, 40-O-(2-Tolylsulfonamidoethyl)-rapamycin, 40-O-[2-(4′

,5′

-Dicarboethoxy-1′

,2′

,3′

-triazol-1′

-yl)-ethyl]-rapamycin, 42-Epi-(tetrazolyl)rapamycin (tacrolimus), 42-[3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate]rapamycin (temsirolimus), (42S)-42-Deoxy-42-(1H-tetrazol-1-yl)-rapamycin (zotarolimus), picrolimus, novolimus, and myolimus.

9. The drug delivery composition of claim 7, wherein the lipophilic agent is rapamycin.

10. The drug delivery composition of claim 1, or claim 2, wherein the polymer comprises any one or more of a linear polymer, branched polymer, dendritic polymer, liquid crystalline polymer, amorphous polymer, semi-crystalline polymer, block co-polymer, tri-block copolymer, graft copolymer, polymer blend, ionomeric polymers, absorbable polymer, and bio-polymer.

11. The drug delivery composition of any one of claims 1-10, wherein at least a portion of the lipophilic agent is crystalline or semi-crystalline.

12. The drug delivery composition of claim 11, wherein at least 50%, 60%, 70%, 75%, 80%, 85%, 90%, 92%, 95%, 98%, 99%, 99.0%, 99.5%, or 99% of the lipophilic agent in the composition is in crystalline or semi-crystalline form.

13. The drug delivery composition of claim 1, or claim 2, formulated for use in, treatment of, or diagnosis of:

chronic diseases;

cancer;

neurologic ailments, conditions, disorders, or diseases;

pain, reproductive ailments, conditions, disorders, or diseases, or as part of a reproductive therapies or treatment;

opthamalogic ailments, conditions, disorders, or diseases;

GI ailments, conditions, disorders, or diseases;

orthopedic ailments, conditions, disorders, or diseases;

surgical applications such as for wound closure, healing, anti-infection, at least;

dental ailments, conditions, disorders, or diseases such as periodontal disease;

anti-viral treatment regimens such as HIV and hepatitis treatment or diagnosis;

vaccines; and

/or aesthetic applications.

14. The drug delivery composition of claim 1, or claim 2, wherein the composition is incorporated into a system comprising a substrate that carries the composition to the administration site or delivery site or treatment site.

15. The drug delivery composition of claim 14, wherein the substrate comprises a medical implant, diagnostic device, interventional device, and/or surgical tool.

16. The drug delivery composition of claim 14, wherein the substrate is a device, tool, or implant for use in orthopedics, neurology, cardiology, vascular treatment or diagnosis, opthamology, urology, gastroenterology, gynecology, obstetrics, aesthetic treatments or diagnosis, surgical applications such as for wound closure, healing, anti-infection, at least;

dental ailments, conditions, disorders, or diseases such as periodontal disease;

anti-viral treatment regimens such as HIV and hepatitis treatment or diagnosis;

vaccines; and

/or aesthetic applications.

17. The drug delivery composition of claim 14, wherein the substrate is a device, tool, or implant for use in allergy and immunology, anesthesiology, critical care medicine, hospice and palliative medicine, pain medicine, sleep medicine, colon and rectal surgery, dermatology, dermatopathology, emergency medicine, critical care medicine, emergency medical services, medical toxicology, sports medicine, undersea and hyperbaric medicine, family medicine, Internal medicine, cardiology, Interventional cardiology electrophysiology, endocrinology, diabetes, metabolism, gastroenterology, geriatric medicine, hematology, Infectious disease, oncology, nephrology, pulmonary disease, rheumatology, hepatology, transplant hepatology, genetics, cytogenetics, molecular genetics, neurological surgery, neurology, nuclear medicine, obstetrics, gynecology, reconstructive surgery, maternal and fetal medicine, reproductive endocrinology, endocrinology, reproductive Infertility, orthopedic surgery, orthopedics, otolaryngology, neurotology, plastic surgery, pathology, blood banking/transfusion medicine, cytopathology, dermatopathology, neuropathology, pediatrics, neonatal-Perinatal medicine, neurodevelopmental disabilities, hematology, pulmology, rheumatology, aerospace medicine, occupational medicine, psychiatry, brain injury medicine, neurophysiology, epilepsy, neuromuscular medicine, neuroradiology, nuclear radiology, radiation oncology, medical physics, vascular and Interventional radiology, surgery, vascular surgery, thoracic and cardiac surgery, and urology.

2. A drug delivery composition comprising a lipophilic agent and a polymer, wherein said composition is a hydrogel, wherein the elution profile is substantially linear, and wherein there is less than 35% lipophilic agent release within the first hour of elution.

6. The drug delivery composition of claim 2, wherein the elution profile is substantially linear once a detectable amount of drug is eluted.