公开(公告)号：EP0774964A1

公开(公告)日：1997-05-28

申请号：EP95928721.0

申请日：1995-08-02

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY ,  THE JOHNS HOPKINS UNIVERSITY

Inventor： BREM, Henry ,  LANGER, Robert, J. ,  DOMB, Abraham, J.

IPC: A61K9 ,  A61K31 ,  A61K38 ,  A61K39 ,  A61K45 ,  A61K47

CPC classification number: A61K9/0085 ,  A61K9/2027 ,  A61K9/2031 ,  A61K9/204 ,  A61K31/337 ,  A61K31/4745 ,  A61K31/555

Abstract: A method and devices for localized delivery of a chemotherapeutic agent to solid tumors, wherein the agent does not cross the blood-brain barrier and is characterized by poor bioavailability and/or short half-lives in vivo, are described. The devices consist of reservoirs which release drug over an extended time period while at the same time preserving the bioactivity and bioavailability of the agent. In the most preferred embodiment, the device consists of biodegradable polymeric matrixes, although reservoirs can also be formulated from non-biodegradable polymers or reservoirs connected to implanted infusion pumps. The devices are implanted within or immediately adjacent the tumors to be treated or the site where they have been surgically removed. The examples demonstrate the efficacy of paclitaxel, camptothecin, and carboplatin delivered in polymeric implants prepared by compression molding of biodegradable and non-biodegradable polymers, respectively. The results are highly statistically significant.

公开(公告)号：EP0476045B1

公开(公告)日：1996-08-28

申请号：EP90909880.8

申请日：1990-06-01

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

Inventor： GERHART, Tobin, N. ,  LAURENCIN, Cato, T. ,  DOMB, Abraham, J. ,  LANGER, Robert, S. ,  HAYES, Wilson, C.

IPC: A61L27/00 ,  A61K47/30 ,  A61K9/22

CPC classification number: A61K9/0024 ,  A61K9/2027 ,  A61K9/2031 ,  A61K9/204 ,  A61L24/0015 ,  A61L2300/406 ,  A61L2300/414 ,  A61L2300/416 ,  A61L2300/604 ,  A61L2430/02

Abstract: Bioerodible polymers which degrade completely into nontoxic residues over a clinically useful period of time, including polyanhydrides, polyorthoesters, polyglycolic acid, polylactic acid, and copolymers thereof, are used for the delivery of bioactive agents, including antibiotics, chemotherapeutic agents, inhibitors of angiogenesis, and simulators of bone growth, directly into bone.

公开(公告)号：EP0712421A1

公开(公告)日：1996-05-22

申请号：EP94925102.0

申请日：1994-07-22

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

Inventor： DOMB, Abraham, J. ,  GREF, Ruxandra ,  MINAMITAKE, Yoshiharu ,  PERACCHIA, Maria, Teresa ,  LANGER, Robert, S.

IPC: G01N33 ,  A61B5 ,  A61K9 ,  A61K47 ,  A61K49 ,  A61K51 ,  C08G63 ,  C08G65 ,  C08G79 ,  C08G81 ,  C08J3

CPC classification number: A61K9/5146 ,  A61K9/5161 ,  A61K47/6921 ,  A61K47/6935 ,  A61K49/223 ,  A61K51/1241 ,  A61K51/1251 ,  A61K2123/00 ,  B82Y5/00 ,  C08G63/664 ,  C08G81/00

Abstract: Particles are provided that are not rapidly cleared from the blood stream by the macrophages of the reticuloendothelial system, and that can be modified to achieve variable release rates or to target specific cells or organs. The particles have a core of a multiblock copolymer formed by covalently linking a multifunctional compound with one or more hydrophobic polymers and one or more hydrophilic polymers, and contain a biologically active material. The terminal hydroxyl group of the poly(alkylene glycol) can be used to covalently attach onto the surface of the particles biologically active molecules, including antibodies targeted to specific cells or organs, or molecules affecting the charge, lipophilicity or hydrophilicity of the particle. The surface of the particle can also be modified by attaching biodegradable polymers of the same structure as those forming the core of the particles. The typical size of the particles is between 180 nm and 10,000 nm, preferably between 180 nm and 240 nm, although microparticles can also be formed as described herein. The particles can include magnetic particles or radiopaque materials for diagnostic imaging, biologically active molecules to be delivered to a site, or compounds for targeting the particles. The particles have a prolonged half-life in the blood compared to particles not containing poly(alkylene glycol) moieties on the surface.

公开(公告)号：EP0368912B1

公开(公告)日：1994-03-16

申请号：EP88906761.7

申请日：1988-07-28

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

Inventor： DOMB, Abraham, J. ,  LANGER, Robert, S.

IPC: A61K31/74 ,  C08G67/04

CPC classification number: A61K9/0024 ,  A61K9/2031 ,  C08G67/04

Abstract: Polyanhydrides with uniform distribution of alkyl and aromatic residues are prepared by melt polycondensation or solution polymerization of p-carboxyphenoxyalkanoic acids or p-carboxyphenylalkanoic acids. These polymers are soluble in common organic solvents and have low melting points, generally in the range of 40-100°C. The polyanhydrides are especially well suited for forming bioerodible matrices in controlled bioactive compound delivery devices. A polymeric matrix formed according to the method described here degrades uniformly during drug release, preventing the wholescale channeling of the bioactive compound into the environment, and eliminating the problem of the presence of the polymer matrix at the site long after drug release. The polymer displays zero-order kinetic degradation profiles over various periods of time (days to months), at a rate useful for controlled drug delivery. Furthermore, a desired degradation rate may be obtained by choosing the appropriate length of the aliphatic moiety.

公开(公告)号：EP0476045A1

公开(公告)日：1992-03-25

申请号：EP90909880.0

申请日：1990-06-01

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

Inventor： GERHART, Tobin, N. ,  LAURENCIN, Cato, T. ,  DOMB, Abraham, J. ,  LANGER, Robert, S. ,  HAYES, Wilson, C.

IPC: A61K9 ,  A61K47 ,  A61L24 ,  A61P19

CPC classification number: A61K9/0024 ,  A61K9/2027 ,  A61K9/2031 ,  A61K9/204 ,  A61L24/0015 ,  A61L2300/406 ,  A61L2300/414 ,  A61L2300/416 ,  A61L2300/604 ,  A61L2430/02

Abstract: Polymères pouvant s'éroder biologiquement se décomposant totalement en des résidus non toxiques pendant une période appropriée aux besoins cliniques. Lesdits polymères, qui comprennent les polyanhydrides, les polyorthoesters, l'acide polyglycolique, l'acide polylactique et leurs copolymères, sont utiles pour introduire directement dans l'os des agents bioactifs, y compris les antibiotiques, les agents chimiothérapeutiques, les inhibiteurs d'angiogénèse, et les simulateurs de croissance osseuse.