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公开(公告)号：WO1990015586A2
公开(公告)日：1990-12-27
申请号：PCT/US1990003136
申请日：1990-06-01
Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Inventor： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , GERHART, Tobin, N. , LAURENCIN, Cato, T. , DOMB, Abraham, J. , LANGER, Robert, S. , HAYES, Wilson, C.
IPC: A61K0
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.
Abstract translation: 用于在临床有用的时间段内完全降解成无毒残留物的生物可降解聚合物，包括聚酐，聚原酸酯，聚乙醇酸，聚乳酸及其共聚物，用于递送生物活性剂，包括抗生素，化学治疗剂，血管生成抑制剂， 和骨骼生长的模拟器，直接进入骨骼。
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公开(公告)号：WO1988006602A1
公开(公告)日：1988-09-07
申请号：PCT/US1988000594
申请日：1988-02-25
Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Inventor： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , DOMB, Abraham, J. , LANGER, Robert, S. , CRAVALHO, Ernest, G. , GOLOMB, Gershon , MATHIOWITZ, Edith , LAURENCIN, Cato, T.
IPC: C08F08/32
CPC classification number: C08F8/32 , C08F2800/10 , C08F8/42 , C08F220/56
Abstract: A method for preparing hydroxamic acid polymers from primary amide polymers wherein polyvinyl monomers such as polyacrylamide are reacted with hydroxyl amine in aqueous solution at room temperature. The low reaction temperature is crucial to producing a high yield (70%) of polymer with hydroxamic acid groups and having a low carboxylic acid content (less than 15%, preferably less than 3%). The polymers display high metal affinity over a broad pH range. The polymers are particularly useful for biomedical applications due to the low carboxylic acid content and for the removal and purification of metals due to the high binding constants and rapid reaction rates.
Abstract translation: 由聚酰胺聚合物制备异羟肟酸聚合物的方法，其中聚乙烯基单体例如聚丙烯酰胺在室温下与羟胺在水溶液中反应。 低反应温度对于用异羟肟酸基团产生高产率（70％）的聚合物和低羧酸含量（小于15％，优选小于3％）是至关重要的。 聚合物在宽pH范围内显示出高的金属亲和力。 由于高的结合常数和快速的反应速率，聚合物由于羧酸含量低以及金属的去除和纯化而特别适用于生物医学应用。
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公开(公告)号：WO1989001006A1
公开(公告)日：1989-02-09
申请号：PCT/US1988002570
申请日：1988-07-28
Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
IPC: C08G67/04
CPC classification number: C08G67/04 , A61K9/2031 , A61L24/0042 , A61L24/046 , A61L2430/02 , C08L73/02
Abstract: A class of unsaturated polyanhydrides having double bonds available for secondary polymerization is disclosed. A crosslinked material having improved or different physical and mechanical properties can be prepared from these polyanhydrides, via secondary polymerization. The synthesis and characteristics of one unsaturated polyanhydride based on fumaric acid and its copolymers with aliphatic and aromatic diacids, prepared by either the melt-polycondensation method or by solution polymerization, is described in detail. These polymers are well suited for use in controlled release drug delivery devices. The polymers can also be used as a bioerodible bone cement where the polymer is first cast as a solution onto a bone fracture and then crosslinked by radiation or radical polymerization to yield a strong, adhesive material.
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公开(公告)号：WO1989001005A1
公开(公告)日：1989-02-09
申请号：PCT/US1988002563
申请日：1988-07-28
Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Inventor： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , DOMB, Abraham, J. , LANGER, Robert, S. , RON, Eyal , GIANNOS, Steven , KOTHARI, Rohit , MATHIOWITZ, Edith
IPC: C08G63/00
CPC classification number: A61K31/335 , A61K31/365 , A61K31/39 , C08G67/04 , C08G69/08 , C08G69/10 , Y10S514/863
Abstract: A method for synthesizing polyanhydrides in solution using coupling agents and a removable acid acceptor to effect a one-step polymerization of dicarboxylic acids. As used in the method, these coupling agents include phosgene, diphosgene, and acid chlorides. Insoluble acid acceptors include insoluble polyamines and crosslinked polyamines such as polyethyleneimine and polyvinylpyridine and inorganic bases such as K2CO3, Na2CO3, NaHCO3, and CaCO3. The only byproduct formed is a removable hydrochloric acid-acid acceptor. Examples are provided of the polymerization of highly pure polyanhydrides using phosgene, diphosgene or an acid chloride as the coupling agent, in combination with either an insoluble acid acceptor or a soluble acid acceptor in a solvent wherein the polymerization byproduct or polymer is insoluble. A particularly important application of these polyanhydrides is in the formation of drug delivery devices containing bioactive compounds. The method is also useful in the polymerization of dicarboxylic acids including heat liable dipeptides of glutamic or aspartic acid.
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公开(公告)号：WO1989000855A1
公开(公告)日：1989-02-09
申请号：PCT/US1988002569
申请日：1988-07-28
Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
IPC: A61K31/74
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.
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Patent Agency Ranking
公开(公告)号：EP0511292B1
公开(公告)日：2000-04-26
申请号：EP91903474.4
申请日：1991-01-07
Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Inventor： DOMB, Abraham, J.
CPC classification number: C08G67/04 , A61K9/2031 , A61K47/58 , A61L31/06 , A61L31/16 , A61L2300/802 , C08L73/02
Abstract: A polyanhydride suitable for use as a matrix material in controlled delivery devices polymerized from monomers of general formula (I), wherein R, R', and R'' are the same or a different aliphatic chain of C1 to C20 or hydrogen; m, n, and p are integers from 0 and 20; y is 0 or 1; and, if y is 0, one of R or R' is not H.
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公开(公告)号：EP0368912A1
公开(公告)日：1990-05-23
申请号：EP88906761.0
申请日：1988-07-28
Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Inventor： DOMB, Abraham, J. , LANGER, Robert, S.
CPC classification number: A61K9/0024 , A61K9/2031 , C08G67/04
Abstract: Des polyanhydrides présentant une distribution uniforme de résidus aromatiques et d'alkyle sont préparés par fusion-polycondensation ou par polymérisation en solution d'acides p-carboxyphénoxyalcanoïques ou d'acides p-carboxyphénylalcanoïques. Ces polymères sont solubles dans des solvants organiques courants et ont des points de fusion bas, généralement de 40 à 100°C. Les polyanhydrides sont particulièrement bien appropriés à la formation de matrice de bio-érosion dans des dispositifs d'apport régulé de composés bioactifs. Une matrice polymère formée selon le procédé ci-décrit se dégrade uniformément pendant la libération des médicaments, empêchant la canalisation totale du composé bioactif dans l'environnement, et éliminant le problème de la présence de la matrice polymère longtemps après la libération du médicament. Le polymère présente des profils de dégradation cynétiques d'ordre zéro sur des périodes de temps diverses (de quelques jours à plusieurs mois) à une vitesse utile à l'apport régulé de médicament. En outre, une vitesse de dégradation désirée peut être obtenue en choisissant la longueur appropriée de la moitié ou fraction aliphatique.
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公开(公告)号：EP0347424A1
公开(公告)日：1989-12-27
申请号：EP88903023.0
申请日：1988-02-25
Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Inventor： DOMB, Abraham, J. , LANGER, Robert, S. , CRAVALHO, Ernest, G. , GOLOMB, Gershon , MATHIOWITZ, Edith , LAURENCIN, Cato, T.
CPC classification number: C08F8/32 , C08F2800/10 , C08F8/42 , C08F220/56
Abstract: Selon un procédé de préparation de polymères d'acide hydroxamique à partir de polymères d'amide primaires, des monomères de polyvinyle, tels que le polyacrylamide, sont mis en réaction avec de l'amine hydroxyle dans une solution aqueuse à la température ambiante. La température basse de réaction est essentielle pour obtenir un haut rendement (70%) de polymère avec des groupes d'acide hydroxamique et ayant une faible teneur en acide carboxylique (moins de 15%, de préférence moins de 3%). Ces polymères présentent une affinité élevée pour des métaux dans une large plage de pH. Ces polymères sont particulièrement utiles pour des applications biomédicales, compte tenu de leur faible teneur en acide carboxylique et pour l'élimination et la purification de métaux, compte tenu de leur constante élevée de liaison et de leur vitesse élevée de réaction.
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9.发明授权CONTROLLED LOCAL DELIVERY OF CHEMOTHERAPEUTIC AGENTS FOR TREATING SOLID TUMORS 无效一种化学实体肿瘤的治疗剂的受控本地投递
公开(公告)号：EP0774964B1
公开(公告)日：2005-03-16
申请号：EP95928721.0
申请日：1995-08-02
Inventor： BREM, Henry , LANGER, Robert, J. , DOMB, Abraham, J.
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.
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公开(公告)号：EP0568651B1
公开(公告)日：2002-04-17
申请号：EP92908387.1
申请日：1992-01-31
Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Inventor： DOMB, Abraham, J. , MANIAR, Manoj , HAFFER, Andrew, T., S.
CPC classification number: C08L67/04 , A61K9/2031 , A61K9/204 , C08L67/02 , C08L73/02 , C08L63/00 , C08L2666/22 , C08L2666/14
Abstract: Blends of polymers having properties distinct from the individual polymer components, and that are suitable for use as carriers of pharmaceutically active agents, are prepared from two or more polyanhydrides, polyesters or mixtures of polyanhydrides and polyesters. The blends have different properties than the polymers used to prepare the blends, providing a means for altering the characteristics of a polymeric matrix without altering the chemical structure of the component polymers. Blends of various polyanhydrides, polyesters, and polyanhydrides and polyesters, containing pharmaceutically active agents, are prepared using solvent mixing or melt mixing procedures. It has been discovered that the rate of release of the agent from the blends is different than the rate of release from the individual polyanhydride and polyester polymer components, being a function of the blend composition.
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