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公开(公告)号：WO1988008300A1
公开(公告)日：1988-11-03
申请号：PCT/US1988001292
申请日：1988-04-20
Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
IPC: A61K09/50
CPC classification number: A61K9/5089 , A61K9/1694 , Y10S514/963 , Y10T428/2987 , Y10T428/2989
Abstract: A single step method for preparation of multilayer polymeric delivery systems. Any two of three different degradable or non-degradable polymers which are not soluble in each other at a particular concentration, as dictated by their phase diagram, can be used. The multi-layer microcapsules produced by the method are distinguished by extremely uniform dimensioned layers of polymer and actual incorporation of the substance to be delivered (e.g. drugs, fertilizers, insecticides, chemical indicators or dyes, chemical reactants and scents or flavoring) into the polymer layers. In the preferred embodiment of the method, two polymers are dissolved in a volatile organic solvent, the substance to be encapsulated is dispersed or dissolved in the polymer solution, the mixture is suspended in an aqueous solution and stirred, and the solvent is slowly evaporated, creating microspheres (10) with an inner core (14) formed by one polymer and an outer layer (12) formed by the second polymer. In another embodiment one polymer may be formed within a layer of the other polymer by increasing the rate of evaporation of the volatile solvent.
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2.发明申请
公开(公告)号：WO1989012464A1
公开(公告)日：1989-12-28
申请号：PCT/US1989002575
申请日：1989-06-13
Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Inventor： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , EDELMAN, Elazer, R. , LANGER, Robert, S. , KLAGSBURN, Michael , MATHIOWITZ, Edith
IPC: A61K47/00
CPC classification number: A61K9/5036 , A61K9/167 , A61K38/1825 , A61K47/61 , Y10S530/813 , Y10S530/815 , Y10S530/816
Abstract: A system for stabilizing fibroblast-derived growth factors, maintaining their bioactivity over a prolonged period of time and controllably releasing them for use is disclosed. The system uses growth factors bound to biocompatible substrates via heparin or heparin derived compounds to maintain the bioactivity of the growth factors. A growth factor bound to a heparin coated substrate can be used independently as a controlled release device, or can be incorporated into a reservoir or matrix type controlled release device to further enhance the controlled release properties. The stabilized growth factors can be implanted into a patient, thereby providing a means for producing an in vivo controlled release of a growth factor to the patient.
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公开(公告)号：WO1989007935A1
公开(公告)日：1989-09-08
申请号：PCT/US1989000348
申请日：1989-01-27
Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Inventor： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , MATHIOWITZ, Edith , LANGER, Robert, S. , WARSHAWSKY, Abraham , EDELMAN, Elazar
IPC: A61K09/00
CPC classification number: A01N25/34 , A61K9/1641 , A61K9/1647 , A61K9/2077 , A61K9/2081 , A61K9/7023 , B01J13/025
Abstract: The present invention is a method to produce composites based on microcapsules or microspheres embedded in continuous polymeric matrices. Both non-bioerodible and erodible polymers can be used. Material can be incorporated into the microcapsules or microspheres for subsequent release. The polymer composites have completely different properties from either a continuous polymer matrix or microcapsules or microspheres and are therefore useful for a wide variety of applications. Figure 1 is a graph of the percent cumulative release of acid orange from microspheres of a polycarboxyphenoxypropane-sebacic acid copolymer.
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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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Patent Agency Ranking
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：EP0358677A1
公开(公告)日：1990-03-21
申请号：EP88904141.0
申请日：1988-04-20
Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Inventor： MATHIOWITZ, Edith , LANGER, Robert, S.
CPC classification number: A61K9/5089 , A61K9/1694 , Y10S514/963 , Y10T428/2987 , Y10T428/2989
Abstract: Le procédé décrit, qui s'effectue en une seule étape, sert à préparer des systèmes de distribution polymères multicouches. Parmi trois polymères différents dégradables ou non dégradables, on peut en utiliser deux qui ne sont pas solubles l'un dans l'autre à une concentration particulière, comme l'indique leur diagramme de phase. Les microcapsules multicouches produites par ledit procédé se distinguent par des couches polymères aux dimensions extrêmement uniformes et par l'incorporation effective dans les couches polymères de la substance à distribuer (telle que médicaments, fertilisants, insecticides, marqueurs ou colorants chimiques, réactifs chimiques et parfums ou arômes). Dans le mode de réalisation préféré dudit procédé, deux polymères sont dissous dans un solvant organique volatil, la substance à mettre en capsule est dispersée ou dissoute dans la solution polymère, le mélange est mis en suspension dans une solution aqueuse et agité, et le solvant est lentement évaporé, ce qui permet la création des microsphères (10) dont un noyau intérieur (14) est formé par le premier polymère et dont une couche externe (12) est formée par le second polymère. Dans un autre mode de réalisation, on peut former un premier polymère dans une couche de l'autre polymère en augmentant la vitesse d'évaporation du solvant volatil.
Abstract translation: 所描述的方法在单个步骤中进行，用于制备多层聚合物分配系统。 在三种不同的可降解或不可降解聚合物中，可使用两种彼此在特定浓度下不可溶的物质，如其相图所示。 通过所述方法制备的多层微胶囊的特征在于具有极其均匀的尺寸和有效掺入物质的聚合物层的聚合物层被分配（如药物，化肥，杀虫剂，化学标记物或染料，化学反应物和香料 或味道）。 在所述方法的优选实施例中，两种聚合物溶解于挥发性有机溶剂中，将胶囊中的物质被分散或溶解在聚合物溶液中，将该混合物悬浮于含水和搅拌的溶液中，并且将溶剂 缓慢地蒸发，这允许产生微球体（10），其中内核（14）由第一聚合物形成并且外层（12）由第二聚合物形成。 在另一个实施方案中，第一聚合物可以通过增加挥发性溶剂的蒸发速率而形成在另一聚合物的一层中。
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公开(公告)号：EP0347424B1
公开(公告)日：1992-03-18
申请号：EP88903023.5
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: 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.
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公开(公告)号：EP0358677B1
公开(公告)日：1993-12-29
申请号：EP88904141.4
申请日：1988-04-20
Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
Inventor： MATHIOWITZ, Edith , LANGER, Robert, S.
CPC classification number: A61K9/5089 , A61K9/1694 , Y10S514/963 , Y10T428/2987 , Y10T428/2989
Abstract: A single step method for preparation of multilayer polymeric delivery systems. Any two of three different degradable or non-degradable polymers which are not soluble in each other at a particular concentration, as dictated by their phase diagram, can be used. The multi-layer microcapsules produced by the method are distinguished by extremely uniform dimensioned layers of polymer and actual incorporation of the substance to be delivered (e.g. drugs, fertilizers, insecticides, chemical indicators or dyes, chemical reactants and scents or flavoring) into the polymer layers. In the preferred embodiment of the method, two polymers are dissolved in a volatile organic solvent, the substance to be encapsulated is dispersed or dissolved in the polymer solution, the mixture is suspended in an aqueous solution and stirred, and the solvent is slowly evaporated, creating microspheres (10) with an inner core (14) formed by one polymer and an outer layer (12) formed by the second polymer. In another embodiment one polymer may be formed within a layer of the other polymer by increasing the rate of evaporation of the volatile solvent.
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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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