Biodegradable biocompatible implant and method of manufacturing same - Patents

Biodegradable biocompatible implant and method of manufacturing same
Agent: Miller Thompson, LLP - Toronto, ON, CA
Inventors: Christine Allen, Justin Grant, Micheline Piquette-Miller
Class: 424450000 (USPTO)
#20050208122
09/22/05

Formulations or delivery systems are provided for controlled release of therapeutically active agents. The delivery systems are composed of polymer and lipid materials and may be prepared as a gel, paste, solution, film, implant or barrier depending on the intended application. The polymer component of the matrix is the naturally occurring biomaterial, chitosan, or a mixture of chitin and chitosan. The lipid component may include phosphatidylcholine, phosphatidylserine, phosphatidylinositol, phosphatidyl or a mixture thereof. The delivery system may be used for delivery of hydrophilic agents, hydrophobic agents or combinations thereof. The therapeutically active agents may be formulated within the matrix as free agents or incorporated into particles. In a preferred embodiment the agents are incorporated into polymeric particles that are dispersed throughout the matrix.
FIELD OF THE INVENTION
[0001] This invention relates in general to a biodegradable, biocompatible implant and method of manufacturing this implant and furthermore relates to the use of this implant in the delivery of pharmaceutically active agents and more particularly the use of a chitosan based material which can be used as an implantable controlled drug delivery composition or system.
SUMMARY OF THE INVENTION
[0015] An object of one aspect of the present invention is to provide improved compatible blends of pharmaceutically active agents within an implantable delivery vehicle as a method to provide sustained, local delivery of drug or drug combinations.
[0016] In accordance with one aspect of the present invention there is provided a drug delivery composition for sustained release or controlled release that includes a physically cross-linked matrix having at least one biodegradable polycationic polymer complexed with a molecule containing a phosphate group.
[0017] In accordance with another aspect of the present invention there is provided a controlled release drug delivery composition including at least one polycationic polymer with at least one molecule containing a phosphate group and at least one pharmaceutically active agent to provide controlled release of a first pharmaceutically active agent when administered to a mammal or patient.
[0018] The drug delivery compositions and/or systems, discussed herein provide controlled release or sustained release and/or protective formulations that comprise of a polycationic polymer such as chitosan, a molecule containing a phosphate group namely a phospholipid, and at least one pharmaceutically active agent.
[0019] The composition may also be comprised of chitosan or a mixture of chitin and chitosan. The phospholipid or lipid component may include phosphatidylcholines, phosphatidylserines, phosphatidylinositols, phosphatidylethanolamines, phosphatidylglycerols, or a mixture thereof. The source of phospholipids used in this invention is a commercially available egg yolk extraction primarily comprised of phosphatidylcholine (>60%) and other phospholipids (40%). Phosphatidylcholine is the principle membrane phospholipid found in human or animal cells and is commonly used in pharmaceutical liposome formulations.
[0020] The pharmaceutically active agents of the present invention can be any of those agents which are generally required to be frequently administered for maintaining the effective blood concentration or an effective concentration of the pharmaceutically active agent content locally. The pharmaceutically active agents of the present invention may be included as a first, second or in multiple quantities. Typical examples of such pharmaceutically active agents are as follows: anti-cancer or anti-proliferative agents--Carmustine, Methotrexate, Carboplatin, Cisplatin, Oxaliplatin, 5-Fluorouracil, 5-Fluorouridine, Cytarabine, Leuprolide acetate, Cyclophosphamide, Vinorelbine, Pilocarpine, Paclitaxel, Mitomycin, Camptothecin, Doxorubicin, Daunorubicin, and the like.
[0021] The drug delivery compositions may also comprise of additives that optimize the properties of the formulation such as: polymeric nanoparticles, liposomes as well as hydrophilic polymers (e.g. poly(ethylene glycol), dextran).
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