| Therapeutic polyanhydride compounds for drug delivery -> Monitor Keywords |
|
|
  Therapeutic polyanhydride compounds for drug deliveryUSPTO Application #: 20070196417Title: Therapeutic polyanhydride compounds for drug delivery Abstract: Polyanhydrides which link low molecular weight drugs containing a carboxylic acid group and an amine, thiol, alcohol or phenol group within their structure into polymeric drug delivery systems are provided. Also provided are methods of producing polymeric drug delivery systems via these polyanhydride linkers as well as methods of administering low molecular weight drugs to a host via the polymeric drug delivery systems. (end of abstract)
Agent: Viksnins Harris & Padys Pllp - St. Paul, MN, US Inventor: Kathryn E. Uhrich USPTO Applicaton #: 20070196417 - Class: 424422000 (USPTO) Related Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Preparations Characterized By Special Physical Form, Implant Or Insert The Patent Description & Claims data below is from USPTO Patent Application 20070196417. Brief Patent Description - Full Patent Description - Patent Application Claims
PRIORITY OF INVENTION [0001] This application is a Continuation of U.S. patent application Ser. No. 09/917,231, (filed 27 Jul. 2001), which is a Continuation-in-Part of U.S. patent application Ser. No. 09/627,215, (filed 27 Jul. 2000), which is incorporated herein by reference. BACKGROUND OF THE INVENTION [0002] Polymers comprising aromatic or aliphatic anhydrides have been studied extensively over the years for a variety of uses. For example, in the 1930s fibers comprising aliphatic polyanhydrides were prepared for use in the textile industry. In the mid 1950s, aromatic polyanhydrides were prepared with improved film and fiber forming properties. More recently, attempts have been made to synthesize polyanhydrides with greater thermal and hydrolytic stability and sustained drug release properties. [0003] U.S. Pat. Nos. 4,757,128 and 4,997,904 disclose the preparation of polyanhydrides with improved sustained drug release properties from pure, isolated prepolymers of diacids and acetic acid. However, these biocompatible and biodegradable aromatic polyanhydrides have radical or aliphatic bonds resulting in compounds with slow degradation times as well as relatively insoluble degradation products unless incorporated into a copolymer containing a more hydrophilic monomer, such as sebacic acid. The aromatic polyanhydrides disclosed in the '128 Patent and the '904 Patent are also insoluble in most organic solvents. A bioerodible controlled release device produced as a homogenous polymeric matrix from polyanhydrides with aliphatic bonds having weight average molecular weights greater than 20,000 and an intrinsic velocity greater than 0.3 dL/g and a biologically active substance is also described in U.S. Pat. No. 4,888,176. Another bioerodible matrix material for controlled delivery of bioactive compounds comprising polyanhydride polymers with a uniform distribution of aliphatic and aromatic residues is disclosed in U.S. Pat. No. 4,857,311. [0004] Biocompatible and biodegradable aromatic polyanhydrides prepared from para-substituted bis-aromatic dicarboxylic acids for use in wound closure devices are disclosed in U.S. Pat. No. 5,264,540. However, these compounds exhibit high melt and glass transition temperatures and decreased solubility, thus making them difficult to process. The disclosed polyanhydrides also comprise radical or aliphatic bonds which can not be hydrolyzed by water. [0005] Polyanhydride polymeric matrices have also been described for use in orthopedic and dental applications. For example, U.S. Pat. No. 4,886,870 discloses a bioerodible article useful for prosthesis and implantation which comprises a biocompatible, hydrophobic polyanhydride matrix. U.S. Pat. No. 5,902,599 also discloses biodegradable polymer networks for use in a variety of dental and orthopedic applications which are formed by polymerizing anhydride prepolymers. [0006] Biocompatible and biodegradable polyanhydrides have now been developed with improved degradation, processing and solubility properties, as well as utilities based upon their degradation products. SUMMARY OF THE INVENTION [0007] The present invention provides biocompatible and biodegradable polyanhydrides which serve as the polymeric backbone linking drug molecules into polymeric drug delivery systems. The polyanhydride polymers of the invention demonstrate enhanced solubility and processability, as well as degradation properties due to the use of hydrolyzable bonds such as esters, amides, urethanes, carbanates and carbonates as opposed to radical or aliphatic bonds. The polyanhydride backbone has one or more groups that will provide a therapeutically active compound upon hydrolysis. The polymers of the invention comprise one or more units of formula (I) in the backbone: --C(.dbd.O)R.sup.1--X--R.sup.2--X--R.sup.1--C(.dbd.O)--O-- (I) wherein each R.sup.1 is group that will provide a therapeutically active compound upon hydrolysis of the polymer; each X is independently an amide linkage, a thioester linkage, or an ester linkage; and R.sup.2 is a linking group; provided that the therapeutically active compound is not an ortho-hydroxy aryl carboxylic acid. [0008] The polyanhydrides of the invention are used to link low molecular weight drug molecules comprising within their molecular structure one carboxylic acid group and at least one amine, thiol, alcohol or phenol group. Accordingly, polyanhydrides of formula (I) serve as the polymer backbone of polymeric drug delivery systems comprising these low molecular weight drugs. [0009] Thus, the present invention also relates to compositions, methods of producing compositions and methods of using compositions comprising a polyanhydride of Formula (I) and low molecular weight drug molecules containing within their structure one carboxylic acid group and at least one amine, thiol, alcohol or phenol group, wherein molecules of the drug are linked to one another via the polyanhydride. These polymeric drug delivery systems provide an effective means to deliver drugs in a controlled fashion to any site of a host. By "host" it is meant to include both animals and plants. [0010] The invention also provides a pharmaceutical composition comprising a polymer of the invention and a pharmaceutically acceptable carrier. [0011] The invention also provides a therapeutic method for treating a disease in an animal comprising administering to an animal in need of such therapy, an effective amount of a polymer of the invention. [0012] The invention also provides a method of delivering a therapeutically active compound to a host comprising administering to the host a biocompatible and biodegradable polymer of the invention, which degrades into the biologically active compound. [0013] The invention provides a polymer of the invention for use in medical therapy, as well as the use of a polymer of the invention for the manufacture of a medicament useful for the treatment of a disease in a mammal, such as a human. [0014] The invention also provides processes and intermediates disclosed herein that are useful for preparing a polymer of the invention. DETAILED DESCRIPTION OF THE INVENTION Definitions [0015] The following definitions are used, unless otherwise described: halo is fluoro, chloro, bromo, or iodo. Alkyl, alkoxy, etc. denote both straight and branched groups; but reference to an individual radical such as "propyl" embraces only the straight chain radical, a branched chain isomer such as "isopropyl" being specifically referred to. Aryl denotes a phenyl radical or an ortho-fused bicyclic carbocyclic radical having about nine to ten ring atoms in which at least one ring is aromatic. Heteroaryl encompasses a radical attached via a ring carbon of a monocyclic aromatic ring containing five or six ring atoms consisting of carbon and one to four heteroatoms each selected from the group consisting of non-peroxide oxygen, sulfur, and N(X) wherein X is absent or is H, O, (C.sub.1-C.sub.6)alkyl, phenyl or benzyl, as well as a radical of an ortho-fused bicyclic heterocycle of about eight to ten ring atoms derived therefrom, particularly a benz-derivative or one derived by fusing a propylene, trimethylene, or tetramethylene diradical thereto. [0016] The term ester linkage means --OC(.dbd.O)-- or --C(.dbd.O)O--; the term thioester linkage means --SC(.dbd.O)-- or --C(.dbd.O)S--; and the term amide linkage means --N(R)C(.dbd.O)-- or --C(.dbd.O)N(R)--, wherein each R is a suitable organic radical, such as, for example, hydrogen, (C.sub.1-C.sub.6)alkyl, (C.sub.3-C.sub.6)cycloalkyl, (C.sub.3-C.sub.6)cycloalkyl(C.sub.1-C.sub.6)alkyl, aryl, heteroaryl, aryl(C.sub.1-C.sub.6)alkyl, or heteroaryl(C.sub.1-C.sub.6)alkyl. The term urethane or carbamate linkage means --OC(.dbd.O)N(R)-- or --N(R)C(.dbd.O)O--, wherein each R is a suitable organic radical, such as, for example, hydrogen, (C.sub.1-C.sub.6)alkyl, (C.sub.3-C.sub.6)cycloalkyl, (C.sub.3-C.sub.6)cycloalkyl(C.sub.1-C.sub.6)alkyl, aryl, heteroaryl, aryl(C.sub.1-C.sub.6)alkyl, or heteroaryl(C.sub.1-C.sub.6)alkyl, and the term carbonate linkage means --OC(.dbd.O)O--. [0017] The term "amino acid," comprises the residues of the natural amino acids (e.g. Ala, Arg, Asn, Asp, Cys, Glu, Gln, Gly, His, Hyl, Hyp, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, and Val) in D or L form, as well as unnatural amino acids (e.g. phosphoserine, phosphothreonine, phosphotyrosine, hydroxyproline, gamma-carboxyglutamate; hippuric acid, octahydroindole-2-carboxylic acid, statine, 1,2,3,4,-tetrahydroisoquinoline-3-carboxylic acid, penicillamine, omithine, citruline, .alpha.-methyl-alanine, para-benzoylphenylalanine, phenylglycine, propargylglycine, sarcosine, and tert-butylglycine). The term also comprises natural and unnatural amino acids bearing a conventional amino protecting group (e.g. acetyl or benzyloxycarbonyl), as well as natural and unnatural amino acids protected at the carboxy terminus (e.g. as a (C.sub.1-C.sub.6)alkyl, phenyl or benzyl ester or amide; or as an .alpha.-methylbenzyl amide). Other suitable amino and carboxy protecting groups are known to those skilled in the art (See for example, Greene, T. W.; Wutz, P. G. M. "Protecting Groups In Organic Synthesis" second edition, 1991, New York, John Wiley & sons, Inc., and references cited therein). [0018] The term "host" includes animals and plants. [0019] The term "peptide" describes a sequence of 2 to 35 amino acids (e.g. as defined hereinabove) or peptidyl residues. The sequence may be linear or cyclic. For example, a cyclic peptide can be prepared or may result from the formation of disulfide bridges between two cysteine residues in a sequence. Preferably a peptide comprises 3 to 20, or 5 to 15 amino acids. Peptide derivatives can be prepared as disclosed in U.S. Pat. Nos. 4,612,302; 4,853,371; and 4,684,620, or as described in the Examples hereinbelow. Peptide sequences specifically recited herein are written with the amino terminus on the left and the carboxy terminus on the right. Continue reading... Full patent description for Therapeutic polyanhydride compounds for drug delivery Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Therapeutic polyanhydride compounds for drug delivery patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. Start now! - Receive info on patent apps like Therapeutic polyanhydride compounds for drug delivery or other areas of interest. ### Previous Patent Application: Pharmaceutical compositions with enhanced stability Next Patent Application: Composite materials based on polysilicic acid and method for the production thereof Industry Class: Drug, bio-affecting and body treating compositions ### FreshPatents.com Support Thank you for viewing the Therapeutic polyanhydride compounds for drug delivery patent info. IP-related news and info Results in 1.37722 seconds Other interesting Feshpatents.com categories: Electronics: Semiconductor , Audio , Illumination , Connectors , Crypto , |
||
