Controlled release of biologically active compounds

#This application claims the benefit of U.S. Application No. 60/968,917, filed Aug. 30, 2007, the disclosure of which is hereby incorporated herein by reference in its entirety.

#This invention is based on the discovery of new class of biodegradable polymers derived from functionalized biologically active compounds that can provide site specific delivery of bioactive compounds upon biodegradation in a controlled manner.

#Biologically active compounds are well known (e.g., aspirin and capsaicin) and have been beneficially administered to patients in need thereof for more than a century. One problem that has been associated with many biologically active compounds is that they can be difficult to dissolve in water or the human body and can also be very difficult to polymerize. Due to the availability and numerous uses of biologically active compounds, it is desirable to enhance their native value by, for example, providing compounds or combinations of compounds with a specific controlled degradation profile or range enabling controlled release of the biologically active compound over an extended, controllable time range.

#As used herein, the term “biologically active compound” refers to a naturally occurring, semi-synthetic, or synthetic agent that provides a pharmaceutically, therapeutically and/or physiologically desirable effect when administered to a mammal (e.g., human). Biologically active compounds capable of incorporation into polymers of the present invention possess at least two functional groups that may each be incorporated into a linkage of the present polymers, for example, an ester or amide linkage such that, upon hydrolysis of the polymer, the biologically active compound is obtained and/or released in a therapeutically effective form. In preferred embodiments, biologically active compounds that may be useful in the present invention have at least one aryl or heteroaryl ring and at least one hydroxyl (OH), substituted or unsubstituted amino, or carboxylic acid substituent on the aromatic or heteroaromatic ring, or functional derivatives of such substituents, such as esters, amides, methyl ethers, and/or glycosides, or other derivatives that would be apparent to those skilled in the art, once placed in possession of the present disclosure.

#The biologically active compounds may also comprise other functional groups (e.g., hydroxyl groups, amine groups, and carboxylic acid groups) that may be used to modify properties of the polymer (e.g. for branching, cross linking and/or appending other molecules (e.g. another biologically active compound) to the polymer, for changing the solubility of the polymer, or for effecting the biodistribution of the polymer). Exemplary therapeutic agents that may be employed as the biologically active compounds in the polymers of the present invention may be found, for example, in: Physicians' Desk Reference, 61st Ed., 2007, Thomson Healthcare Company; USPN Dictionary of USAN and International Drug Names, 2000, The United States Pharmacopoeia Convention, Inc., Rockville, Md.; and The Merck Index, 14th Ed., 2007, John Wiley & Sons, the disclosures of each of which are hereby incorporated herein by reference, in their entireties. One skilled in the art can readily select therapeutic agents that possess the necessary functional groups for incorporation into the polymers of the invention from these sources, once placed in possession of the teachings in the present disclosure.

#Therapeutic agents that may be incorporated into the monomers, oligomers or polymers of the present invention include, for example, suitably functionalized analgesics or general or local anesthetics, anti-convulsants, anti-diabetic agents, anti-fibrotic agents, anti-infectives, anti-bacterials, anti-fungals, anti-neoplastics, cardioprotective agents, cardiovascular agents, anti-thrombotics, central nervous system stimulants, cholinesterase inhibitors, contraceptives, deodorants, dopamine receptor agonists, erectile dysfunction agents, fertility agents, gastrointestinal agents, gout agents, hormones, immunomodulators, immunosuppressive, migraine agents, non-steroidal anti-inflammatory drugs (NSAIDs), motion sickness agents, muscle relaxants, nucleoside analogs, neurodegenerative agents (e.g., Parkinson's disease), obesity agents, ophthalmic agents, osteoporosis agents, parasympatholytics, parasympathommetics, anti-anesthetics, prostaglandins, psychotherapeutic agents, respiratory agents, sedatives, hypnotics, skin and mucous membrane agents, smoking cessation agents, sympatholytics, urinary tract agents, vaginal agents, and vasodilators, and the like (see Physicians' Desk Reference, 61st Ed., 2007, Thomson Health Care, the disclosures of which are hereby incorporated herein by reference, in their entireties).