CN103122132A - 用于医疗器械的可生物吸收聚合物组合物 - Google Patents

用于医疗器械的可生物吸收聚合物组合物 Download PDF

Info

Publication number
CN103122132A
CN103122132A CN2013100256704A CN201310025670A CN103122132A CN 103122132 A CN103122132 A CN 103122132A CN 2013100256704 A CN2013100256704 A CN 2013100256704A CN 201310025670 A CN201310025670 A CN 201310025670A CN 103122132 A CN103122132 A CN 103122132A
Authority
CN
China
Prior art keywords
lactide
rac
poly
altogether
composition
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN2013100256704A
Other languages
English (en)
Other versions
CN103122132B (zh
Inventor
G·L·萨奇尔
R·J·科顿
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Obasnitz medical Sdn Bhd
Original Assignee
Orbus Medical Technologies Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Orbus Medical Technologies Inc filed Critical Orbus Medical Technologies Inc
Priority claimed from CN2007800347513A external-priority patent/CN101522754B/zh
Publication of CN103122132A publication Critical patent/CN103122132A/zh
Application granted granted Critical
Publication of CN103122132B publication Critical patent/CN103122132B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/148—Materials at least partially resorbable by the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/82—Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/86—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure
    • A61F2/90—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure
    • A61F2/91—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes
    • A61F2/915—Stents in a form characterised by the wire-like elements; Stents in the form characterised by a net-like or mesh-like structure characterised by a net-like or mesh-like structure made from perforated sheet material or tubes, e.g. perforated by laser cuts or etched holes with bands having a meander structure, adjacent bands being connected to each other
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/14—Macromolecular materials
    • A61L27/26—Mixtures of macromolecular compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/58—Materials at least partially resorbable by the body
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/04—Macromolecular materials
    • A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/18—Materials at least partially X-ray or laser opaque
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C45/00—Injection moulding, i.e. forcing the required volume of moulding material through a nozzle into a closed mould; Apparatus therefor
    • B29C45/0053—Injection moulding, i.e. forcing the required volume of moulding material through a nozzle into a closed mould; Apparatus therefor combined with a final operation, e.g. shaping
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C48/00—Extrusion moulding, i.e. expressing the moulding material through a die or nozzle which imparts the desired form; Apparatus therefor
    • B29C48/001—Combinations of extrusion moulding with other shaping operations
    • B29C48/0022—Combinations of extrusion moulding with other shaping operations combined with cutting
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C71/00—After-treatment of articles without altering their shape; Apparatus therefor
    • B29C71/0063—After-treatment of articles without altering their shape; Apparatus therefor for changing crystallisation
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
    • C08G63/91—Polymers modified by chemical after-treatment
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L67/00—Compositions of polyesters obtained by reactions forming a carboxylic ester link in the main chain; Compositions of derivatives of such polymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2210/00—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2210/0004—Particular material properties of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof bioabsorbable
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/606—Coatings
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C2793/00—Shaping techniques involving a cutting or machining operation
    • B29C2793/0009—Cutting out
    • B29C2793/0018—Cutting out for making a hole
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
    • B29C2793/00—Shaping techniques involving a cutting or machining operation
    • B29C2793/009—Shaping techniques involving a cutting or machining operation after shaping
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2067/00—Use of polyesters or derivatives thereof, as moulding material
    • B29K2067/04—Polyesters derived from hydroxycarboxylic acids
    • B29K2067/046—PLA, i.e. polylactic acid or polylactide
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2105/00—Condition, form or state of moulded material or of the material to be shaped
    • B29K2105/0085—Copolymers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2995/00—Properties of moulding materials, reinforcements, fillers, preformed parts or moulds
    • B29K2995/0037—Other properties
    • B29K2995/0041—Crystalline
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29K—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES B29B, B29C OR B29D, RELATING TO MOULDING MATERIALS OR TO MATERIALS FOR MOULDS, REINFORCEMENTS, FILLERS OR PREFORMED PARTS, e.g. INSERTS
    • B29K2995/00—Properties of moulding materials, reinforcements, fillers, preformed parts or moulds
    • B29K2995/0037—Other properties
    • B29K2995/0059—Degradable
    • B29K2995/006—Bio-degradable, e.g. bioabsorbable, bioresorbable or bioerodible
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
    • B29L—INDEXING SCHEME ASSOCIATED WITH SUBCLASS B29C, RELATING TO PARTICULAR ARTICLES
    • B29L2031/00—Other particular articles
    • B29L2031/753—Medical equipment; Accessories therefor
    • B29L2031/7532—Artificial members, protheses
    • B29L2031/7534—Cardiovascular protheses
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L2203/00—Applications
    • C08L2203/02—Applications for biomedical use
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L2205/00—Polymer mixtures characterised by other features
    • C08L2205/02—Polymer mixtures characterised by other features containing two or more polymers of the same C08L -group
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T428/00—Stock material or miscellaneous articles
    • Y10T428/13—Hollow or container type article [e.g., tube, vase, etc.]
    • Y10T428/1352—Polymer or resin containing [i.e., natural or synthetic]
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T428/00—Stock material or miscellaneous articles
    • Y10T428/13—Hollow or container type article [e.g., tube, vase, etc.]
    • Y10T428/1352—Polymer or resin containing [i.e., natural or synthetic]
    • Y10T428/139—Open-ended, self-supporting conduit, cylinder, or tube-type article

Abstract

本发明提供了一种生物可降解的生物相容性无毒聚合物组合物，它包括一种基质材料以及一种共聚物或三聚物添加剂，所述基质材料例如可结晶的聚合物、共聚物或三聚物。本发明还提供了由该组合物制备的医疗器械。

Description

用于医疗器械的可生物吸收聚合物组合物
本申请是申请日为2007年07月20日的200780034751.3号发明专利申请(发明名称：用于医疗器械的可生物吸收聚合物组合物)的分案申请。
相关申请的互相参引
本申请要求享有2006年7月20日提交的美国临时申请60/807,932以及2006年10月20日提交的美国临时申请60/862,433的优先权。
本说明书中所引用的所有参考文献以及它们的参考文献，当适用于教导其它的或备选的详情、特征和/或技术背景时，通过引证的方式全文纳入本说明书中。
技术领域
在本发明的实施方案中公开了一种新的聚合物组合物，它包括一种基质材料以及一种聚合物或共聚物或三聚物添加剂，所述基质材料包括一种或多种可生物吸收的聚合物、共聚物或三聚物。具体而言，当这种新的组合物被用于制造植入物时，容许发生一种“软”降解机理，从而使得该组分聚合物的降解对周围组织的伤害较小。
背景技术
发现使用金属支撑管(stenting)中一个长期的问题是位于血管中的支架会形成瘢痕组织包被层，即所谓的再狭窄过程。此外，金属或聚合物非可吸收的支架会阻止血管管腔重塑和扩张。已尝试多种方法来避免或愈合组织损伤以及降低免疫反应的补体激活。而且，在植入物和/或其组分材料降解后需要降低炎症应答以及降低发生创伤的可能性。发现想要的改善目标为需要提高用于植入——特别是血管中植入——的医疗器械的形状和结构的柔性。
多种市售可生物吸收聚合物中包括聚-α-酯(例如丙交酯(即L-丙交酯和D，L-丙交酯))和乙交酯、聚酯醚(即聚二噁烷酮)以及聚碳酸酯(即乙交酯或丙交酯-共-碳酸亚丙酯(Tri-methylene-carbonate))以及基于酪氨酸的聚碳酸酯。正在开发可市售的特别是用于不同的给药模式的许多其它的可生物吸收聚合物，所述聚合物包括聚乙二醇-共-丙交酯、聚酐、聚原酸酯、聚酯-酰胺或氰基丙烯酸酯。
本发明的发明人已认识到需要开发一种相容性的共混聚合物用于植入物，例如支架和血管合成植入物；所述共混聚合物在该医疗器械体内使用时可向基质聚合物提供一种韧化机制。他们已假设韧化机制可通过赋予基质聚合物额外的分子自由体积以促进充分的分子运动来使得在生理条件下——尤其是当将其它分子作用力(molecular strain)赋予该植入物时——发生重结晶而被实施。他们已建立理论认为，增加的分子自由体积也可提高水吸收的速率从而增加塑化效果以及提高本体降解动力学。
参引文献
参引2003年8月19日授权的美国专利6,607,548B2(Inion Ltd)，该文献公开了多种使用一种基于乳酸或乙醇酸的聚合物或共聚物与一种或多种共聚物添加剂共混而制得的组合物是可生物相容的且可生物再吸收的。据称根据该548专利公开内容制得的植入物为可冷弯曲(coldbendable)且无裂纹或破裂。还参引EP0401844，其公开了一种聚L-丙交酯与聚L-DL-丙交酯的混合物。还参引美国专利5,317,064，其公开了多种聚丙交酯立体复合组合物。
发明内容
本发明提供了这样一种新的聚合物组合物，该组合物可在体内进行“软”降解从而使得降解时对周围组织友好(例如更少的炎症应答以及使得植入物降解时创伤的可能降低)。该聚合物组合物包括一种基质材料以及一种共聚物或三聚物添加剂；所述基质材料如可生物吸收聚合物、共聚物或三聚物，根据它们在体内进行水解和/或酶促降解和吸收的能力进行选择。
所述新的聚合物组合物可包括一种共混聚合物，该共混物被优化以获得提高的亲水性从而减少补体激活并尽可能减小或避免调理作用(见Dong and Feng，J ot Biomedical Materials Research part A DOI10.1002，2006)。为了改善亲水性，可配制所述新的聚合物组合物以提供增加的分子自由体积，使得水的吸收以及水吸收的速率提高，从而增加塑化效果以及提高本体降解动力学。附加的分子自由体积也可用于促进充分的分子运动来使得在生理条件下——尤其是当将组合物上的作用力产生其它的分子作用力时——发生重结晶。
在一个实施方案中，提供了这样一种包括一种生物可降解支架的聚合物/共混聚合物植入物，该支架显示出卷曲地固定在载体系统上的柔性并在植入体内后显示出由于聚合物/共混聚合物结晶而引起的弹性支撑力。该植入物可包括，例如具有可安装于器官空间——例如血管系统，包括心血管系统——中的结构的管形可膨胀的支架。所述支架可具有平衡了弹性、刚性和柔性的机械性能。
在一个实施方案中，聚合物组合物和/或制剂含有一种作为基质的诸如聚(L-丙交酯)和/或聚(D-丙交酯)的聚合物或者其共聚物。对于共聚物组合物，该共聚物可以嵌段共聚物的形式或以“嵌段的”无规共聚物的形式合成。可选择共聚物的丙交酯链长度以使其充分长足以结晶。为了例如提高降解动力学而缩短的降解时间可通过使用较低分子量组合物和/或更具亲水性或可能进行水解链断裂的基质聚合物来获得。
任选地，所述实施方案组合物包括改性共聚物，其可被混合以连接基质聚合物；所述改性共聚物包括例如聚L(或D)-丙交酯-共-碳酸亚丙酯或聚L(或D)-丙交酯-共-ε-己内酯。在所述共聚物改性的共聚物实施方案中，该组合物使得可产生这样的晶体结构，即该晶体结构可提高医疗器械的机械性能、提高加工条件以及提供交联部分——例如作用力导致的热交联——结晶的可能。改性的聚合物或共聚物也可用于提高降解动力学，例如用一个ε-己内酯共聚物部分，其中己内酯仍为无定形的，而所得部分更易水解。
在另一个实施方案的组合物中，基质共聚物包括L-丙交酯/D-丙交酯，其中一个链部分足够长并且空间上不受阻，从而与另一个丙交酯的部分结晶。任选的与基质共聚物共聚的单体包括尺寸较小的部分，例如乙交酯、聚乙二醇(PEG)或单甲氧基封端的PEG(PEG-MME)。
在另一个实施方案中，可包括PEG共聚物，例如PEG部分约1％的AB二嵌段或ABA三嵌段，可在维持丙交酯的机械性能的情况下使用(见Enderlie and Buchholz SFB May2006)。PEG或PEG-MME共聚物的引入也可用于促进药物附着到聚合物上，例如与药物洗脱医疗器械连接。
本发明实施方案中的亲水组合物想要容许适于一种“软”或非常缓慢的降解机理，从而使得降解进行时对周围组织友好(植入物降解时炎症应答更少以及使创伤的可能降低)。选择一种用于基质聚合物或添加剂或两者的具有提高的亲水性能的聚合物或共聚物，从而使得该共混聚合物可减少补体激活并尽可能减小或避免调理作用。
在一个实施方案的组合物中，选择聚合物以提供外消旋物或立体复合物晶体结构。例如，共聚物可以一个足以形成外消旋晶体结构的比例含有D-丙交酯和L-丙交酯。由所述聚合物组合物制得的支架可通过在从卷曲的状态膨胀至扩张或植入的状态的径向应变期间实现的分子再定向和结晶来提高机械性能。更具体而言，所述实施方案中的管状支架可在被卷曲到一个载体/植入器械上后于成更陡角度的曲折支柱处进行外消旋物结晶，同时在别处仍然保持基本无定形的基质。当管形支架包括箍结构时，可制备所述聚合物以能够在移植期间于正交展开延伸环或箍结构中结晶，对断裂产生强的抗性。
在另一个实施方案中，促进基质聚合物(如聚L-丙交酯或聚D-丙交酯)与分别具有相同的丙交酯部分的改性共聚物(如LPLA-TMC或DPLA-TMC)之间的交联部分结晶。
聚合物实施方案的组合物也可被改性以赋予医疗器械特定的功能。因此，该聚合物可含有药物形式或其它药剂形式的填充剂，例如内源酶的小分子抑制剂、不透射线标记物(粉末或其它合适的微粒)以及其它因子。
本发明的组合物可包括药剂如他克莫司(tacrolimus)、西罗莫司(sirolimus)、依维莫司(everolimus)、依前列醇(prostacyclin)、依前列醇类似物、α-降钙素基因相关多肽(α-CGRP)、α-降钙素基因相关多肽类似物或α-降钙素基因相关多肽受体激动剂，哌唑嗪(prazosin)，单核细胞趋化蛋白-1(MCP-1)，免疫抑制药如雷帕霉素(rapamycin)、抑制平滑肌细胞迁移和/或增殖的药物、抗凝血药如凝血酶抑制剂、免疫调节药如血小板因子4和CXC趋化因子，CX3CR1受体家族抑制剂，抗炎药、甾族化合物如双氢表雄甾酮(DHEA)、睾酮(testosterone)、雌激素如17β-雌二醇(17β-estradio1)，他汀类药物如辛伐他汀(simvastatin)和氟伐他汀(fluvastatin)，PPAR-α-配体如非诺贝特(fenofibrate)和其它降脂药物，PPAR-8和PPAR-γ激动剂如罗格列酮(rosiglitazone)，PPAR-双αγ激动剂、LBM-642、核因子如NF-κβ、胶原合成抑制剂、血管扩张药如乙酰胆碱(acetylcholine)、阿糖腺苷(adenosine)、5-羟色胺(5-hydroxytryptamine或serotonin)、P物质、肾上腺髓质素、促使内皮细胞生长以及分化的生长因子如碱性成纤维细胞生长因子(bFGF)、血小板源性生长因子(PDGF)、内皮细胞生长因子(EGF)、血管内皮细胞生长因子(VEGF)，蛋白酪氨酸激酶抑制剂如米哚妥林(Midostaurin)和伊马替尼(imatinib)或任何抗血管新生抑制剂化合物，抑制成熟白细胞粘附的肽或抗体、抗生素/杀菌剂以及其它物质如速激肽、神经激肽或唾液腺激肽(sialokinin)、速激肽NK受体激动剂，PDGF受体抑制剂如MLN-518及其衍生物、丁酸及丁酸衍生物葛根黄素(puerarin)、纤连蛋白、红细胞生成素(erythropoietin)、达贝泊汀(darbepotin)、丝氨酸蛋白酶-1(SERP-1)等。
本发明实施方案中包括由所述聚合物组合物制得的器械。所述器械包括植入患者体内的医疗器械，例如但不限于生物可降解的支架、支架移植物、血管合成移植物、矫形外科装置、神经导管、颌面颅器械、导管、血管分流器或瓣膜。所述器械可具有可生物吸收性能。所述植入器械可包括用于将植入物植入体内的结构。例如，所述植入物可包括使得该医疗器械的合适部件之间相互作用的卡扣结构以使得该器械保持在一种小尺寸的状态，该状态可帮助其植入，并且可帮助其与用于其植入的载体装置之间的相互作用(例如确保其在载体装置上而无移动)。
本发明的实施方案也涉及制备生物可降解聚合物组合物的方法以及由本文所公开的聚合物组合物制备医疗器械的方法。
因此，本发明具体地涉及以下各项：
1.一种可结晶的可生物吸收聚合物组合物，包括：一种选自聚(L-丙交酯)部分和/或聚(D-丙交酯)部分以及/或者其嵌段共聚物或嵌段无规共聚物的基质聚合物。
2.根据第1项的可结晶的可生物吸收聚合物组合物，还包括一种连有改性共聚物的基质聚合物，该基质聚合物包括聚(L-丙交酯)部分和/或聚(D-丙交酯)部分；所述改性共聚物包括嵌段共聚物形式或嵌段无规共聚物形式的聚(L-丙交酯-共-碳酸亚丙酯)或聚(D-丙交酯-共-碳酸亚丙酯)和(L-丙交酯-共-ε-己内酯)或聚(D-丙交酯-共-ε-己内酯)，其中丙交酯链长度足以使得进行交联部分结晶。
3.根据第1项的可结晶的可生物吸收聚合物组合物，其中该聚合物组合物熔体在聚L和聚D丙交酯部分之间形成丙交酯外消旋物立体复合物晶体结构。
4.根据第1项的可结晶的可生物吸收聚合物组合物，其中该聚合物组合物熔体通过以下部分形成丙交酯外消旋物立体复合物晶体结构，所述部分包括：
连有聚(L-丙交酯-共-碳酸亚丙酯)或聚(L-丙交酯-共-ε-己内酯)的聚L-丙交酯与聚D-丙交酯；
连有聚(L-丙交酯-共-碳酸亚丙酯)或聚(L-丙交酯-共-ε-己内酯)的聚D-丙交酯；
连有聚(D-丙交酯-共-碳酸亚丙酯)或聚(L-丙交酯-共-ε-己内酯)的聚L-丙交酯；
连有聚(D-丙交酯-共-碳酸亚丙酯)或聚(L-丙交酯-共-ε-己内酯)的聚L-丙交酯与聚D-丙交酯；
连有(聚D-丙交酯-共-碳酸亚丙酯)或聚(L-丙交酯-共-ε-己内酯)的聚L-丙交酯-共-PEG；以及
连有聚(L-丙交酯-共-碳酸亚丙酯)或聚(L-丙交酯-共-ε-己内酯)的聚D-丙交酯-共-PEG。
5.根据第1项的可结晶的可生物吸收聚合物组合物，其中所述基质聚合物以重量计占该组合物的约70％至约85％、或约70％至约80％。
6.根据第1项的可结晶的可生物吸收聚合物组合物，其中所述基质聚合物的70重量％为聚L-丙交酯且30重量％为改性共聚物聚L-丙交酯-共-TMC。
7.根据第1项的可结晶的可生物吸收聚合物组合物，其中所述改性共聚物不高于该组合物的约40％。
8.根据第1项的可结晶的可生物吸收聚合物组合物，其中该组合物的残留单体浓度小于0.5％或优选小于0.3％。
9.一种可生物吸收的支架聚合物，包括一种可结晶的组合物，该组合物包括一种连有改性共聚物的聚L-丙交酯或聚D-丙交酯的基质聚合物；所述改性共聚物包括嵌段共聚物形式或嵌段无规共聚物形式的聚L(或D)-丙交酯-共-碳酸亚丙酯或聚L(或D)-丙交酯-共-ε-己内酯，其中丙交酯链长度足以进行交联部分结晶。
10.根据第9项的可生物吸收的支架聚合物，其中所述基质聚合物以重量计占该组合物的约60％至约90％、或约70％至约80％。
11.根据第9项的可生物吸收的支架聚合物，其中所述基质聚合物的70重量％为聚L-丙交酯且30重量％为改性共聚物聚L-丙交酯-共-TMC。
12.根据第9项的可生物吸收的支架聚合物，其中所述改性共聚物不高于该组合物的约40％。
13.根据第9项的可生物吸收的支架聚合物，其中该组合物的残留单体浓度小于0.5％或优选小于0.3％。
14.根据第9项的可生物吸收的支架聚合物，其中该组合物被制备成在结构上可在聚合物基质内包含或结合药物。
15.根据第9项的可生物吸收支架聚合物，其中该药物或其它添加剂可通过共价键、非极性键以及酯或类似的生物可逆结合而被结合。
16.一种用于心血管的可膨胀的管状支架的聚合物组合物，其中所述支架包括一种连有改性共聚物的聚L-丙交酯或聚D-丙交酯的基质聚合物；所述改性共聚物包括嵌段共聚物形式或嵌段无规共聚物形式的聚L(或D)-丙交酯-共-碳酸亚丙酯或聚L(或D)-丙交酯-共-ε-己内酯，其中丙交酯链长度足以进行交联部分结晶。
17.根据第16项的组合物，其中所述支架包括一种以重量计占该组合物约60％至约90％、或约70％至约80％的基质聚合物。
18.根据第16项的组合物，其中所述支架包括一种具有70重量％聚L-丙交酯与30重量％改性共聚物聚L-丙交酯-共-TMC的基质聚合物。
19.根据第16项的组合物，其中所述改性共聚物不高于该组合物的约40％。
20.根据第16项的组合物，其中该支架显示出通过刚性和柔性特征的结合而具有的结构弹性，以使得该聚合物器械的合适部件之间具有卡扣的相互作用。
21.根据第16项的组合物，其中该组合物的残留单体浓度小于0.5％或优选小于0.3％。
22.一种可生物吸收的聚合物植入物，包括一种在单一步骤中熔融共混挤压制备的聚合物组合物，该聚合物组合物包括一种可结晶的组合物，该可结晶的组合物包括一种包括了聚(L-丙交酯)部分和/或聚(D-丙交酯)部分以及/或者其共聚物的基质聚合物。
23.制备一种根据第22项的可生物吸收的聚合物植入物的方法，还包括：
将一种包括一种可结晶组合物的聚合物组合物共混，所述可结晶组合物包括一种连有改性共聚物的基质聚合物，所述基质聚合物包括聚(L-丙交酯)部分和/或聚(D-丙交酯)部分；所述改性共聚物包括嵌段共聚物形式或嵌段无规共聚物形式的聚(L-丙交酯-共-碳酸亚丙酯)和/或聚(D-丙交酯-共-碳酸亚丙酯)和/或聚(L-丙交酯-共-ε-己内酯)和/或(D-丙交酯-共-ε-己内酯)，其中丙交酯链长足够长以便于发生交联部分结晶；
将所述聚合物组合物成型或挤出形成所述具有管状结构的植入物；以及
切割所述植入物以形成所需式样。
24.根据第23项的方法，其中所述聚合物组合物通过刚性和柔性特征的结合而影响结构弹性，以使得该聚合物器械的合适部件之间具有卡扣相互作用。
25.根据第23项的方法，其中该聚合物组合物熔体在L-丙交酯和D-丙交酯部分之间形成丙交酯外消旋物立体复合物晶体结构。
26.根据第23项的方法，其中该聚合物组合物在以下各部分之间形成丙交酯外消旋物立体复合物晶体结构，所述部分包括：
连有聚(L-丙交酯-共-碳酸亚丙酯)或聚(L-丙交酯-共-ε-己内酯)的聚D-丙交酯和聚L-丙交酯；
连有聚(L-丙交酯-共-碳酸亚丙酯)或聚(L-丙交酯-共-ε-己内酯)的聚D-丙交酯；
连有聚(D-丙交酯-共-碳酸亚丙酯)或聚(L-丙交酯-共-ε-己内酯)的聚L-丙交酯；
连有聚(D-丙交酯-共-碳酸亚丙酯)或与聚(L-丙交酯-共-ε-己内酯)的聚D-丙交酯和聚L-丙交酯；
连有(聚D-丙交酯-共-碳酸亚丙酯)或聚(L-丙交酯-共-ε-己内酯)的聚L-丙交酯-共-PEG；以及
连有聚(L-丙交酯-共-碳酸亚丙酯)或聚(L-丙交酯-共-ε-己内酯)的聚D-丙交酯-共-PEG。
27.根据第23项的方法，其中所述改性共聚物不高于该组合物的约40％。
28.根据第23项的方法，其中该组合物的残留单体浓度小于0.5％或优选小于0.3％。
附图说明
图1图示了LPLA/LPLA/TMC非外消旋混合物与仅交联部分外消旋的DPLA/LPA/TMC和具有其它外消旋结构的DPLA/LPLA/LPLA-TMC的再结晶的模数变化；
图2A和图2B分别图示了外消旋聚合物和无外消旋结构的聚合物的DSC曲线：如图所示，显示出外消旋熔化物的+外消旋物曲线和-外消旋物曲线明显不同。
图3A-3G图示了支架医疗器械的不透射线标记储存处的实施方案方法：如(a)-(d)中所示，不透射线材料可被挤入装置(g)中所含的空穴中。如截面图(e)和(f)所示，所述空穴可为一个透孔。
图4A-4C图示了具有不透射线标记物的支架的不同支架式样。如图所示，不透射线标记物可被置于支架式样上的不同位置，同时仍可用不透射线检测方法进行检测。
图5A和图5B图示了具有不透射线标记物的支架材料的平面图。如图5A和图5B所示，不透射线标记物可被排列成在成像时或使用其它检测方法时更容易识别的结构。
图6示出了具有实施方案中所述的不透射线标记物式样的实际支架的总透视图，所述不透射线标记物式样各自位于曲折支柱的连接点处。图7示出了图6的被不透射线标记的支架的一部分的近视图。
图8示出了配置于带囊导管上的本发明的支架实施方案的透视图。
图9图示了包含环结构的充分膨胀的可生物吸收支架，该环结构表示充分结晶的定位(holding)环或箍。
图10A和图10B图示了表明单Tg的DSC热流曲线，并且10B示出了表明双Tg的DSC热流曲线。
具体实施方式
在本文的实施方案中，举例说明了多种用于可生物吸收共混聚合物的组合物、制备该组合物的方法以及由所述可生物吸收共混聚合物制得的医疗器械。
现将以下命名法以及基于所存在的单体类型的聚合物命名法一起使用。
LPLA：聚(L-丙交酯)
LPLA-PEG：聚(聚-L-丙交酯-聚乙二醇)
DPLA：聚(D-丙交酯)
DPLA-TMC：聚(聚-D-丙交酯-共-碳酸亚丙酯)
DLPLA：聚(DL-丙交酯)，外消旋共聚物D-共-L-丙交酯
LDPLA：聚(L-共-D-丙交酯)
LDLPLA：聚(L-共-D-丙交酯)，根据单体引入的方法命名
PGA：聚(乙交酯)
PDO：聚(二噁烷酮)(商标为PDS)
SR：“自增强”(一种加工方法)
TMC：碳酸亚丙酯
PCL：聚(ε-己内酯)
LPLA-TMC：聚(聚L-丙交酯-共-碳酸亚丙酯)
LPLG：聚(L-丙交酯-共-乙交酯)
POE：聚原酸酯
在本发明的一个实施方案中，该组合物包括一种聚(L-丙交酯)或聚(D-丙交酯)的基质聚合物。有利的基质聚合物组合物包括聚(L-丙交酯)和聚(D-丙交酯)的共混物。其它有利的基质聚合物组合物包括含有单体摩尔配比为10-30％的D，L-丙交酯的聚(L-丙交酯-共-D，L-丙交酯)或聚(D-丙交酯-共-D，L-丙交酯)，以及含有单体摩尔配比为10-20％的乙交酯的聚(L-丙交酯-共-乙交酯)或聚(D-丙交酯-共-乙交酯)。
另一个实施方案体现一种基质聚合物，其特征为改性共聚物连接于基质聚合物的聚(L-丙交酯)部分和/或聚(D-丙交酯)部分上；所述改性共聚物包括嵌段共聚物形式或嵌段无规共聚物形式的聚(L-丙交酯-共-碳酸亚丙酯)或聚(D-丙交酯-共-碳酸亚丙酯)和(L-丙交酯-共-ε-己内酯)，或者聚(D-丙交酯-共-ε-己内酯)，其中丙交酯链的长度足以进行交联部分结晶。
在另一个实施方案中，该聚合物组合物使得在L和D部分之间形成丙交酯外消旋物(立体复合物)晶体结构，以进一步提高可生物吸收聚合物医疗器械的机械性能。该外消旋物(立体复合物)晶体结构的形成可由例如以下的物质的配制得到：
聚L-丙交酯与聚D-丙交酯与聚L-丙交酯-共-TMC；
聚D-丙交酯与聚L-丙交酯-共-TMC；
聚L-丙交酯与聚D-丙交酯-共-TMC；
聚L-丙交酯与聚D-丙交酯与聚D-丙交酯-共-TMC；
聚L-丙交酯-共-PEG与聚D-丙交酯-共-TMC；以及
聚D-丙交酯-共-PEG与聚L-丙交酯-共-TMC。
该实施方案的聚丙交酯外消旋组合物可具有一个特别有利的特征，该特征在于该组合物“可冷形成或弯曲”而不需加热。本发明的可冷弯曲支架不需要加热就可变得足够柔韧以卷曲于载体装置上或容纳在不规则形状的器官空间内。冷弯曲环境温度被定义为不超过30℃的室温。可冷弯曲支架，例如在进行移植时可提供足够的柔性，从而使得膨胀的支架器械可进入器官空间如搏动的血管腔中。例如对于支架而言，需要利用这样的聚合物组合物，它在制造后提供大部分的无定形聚合物部分，该部分可结晶——特别是当二级嵌套或末端定位的曲折支柱时，同时该支架在为植入而进行球囊扩张时由于被拉伸而拉紧。实施方案的所述可冷弯曲的聚合物支架不易碎并且在植入体内的具有表面轮廓的空间上之前不必预热即可处于柔韧的状态。可冷弯曲性使得这些共混物可在室温下进行卷曲且无裂纹；并且此外，这些共混物可在生理条件下进行卷曲且无裂纹。
可加工本发明实施方案的聚-丙交酯外消旋组合物和非外消旋组合物以具有嵌段部分，从而使得甚至在将抗压改性剂加入该共混组合物的情况下交联部分结晶。所述共混物使得通过获得单Tg或双Tg的(熔融玻璃转化温度)来设计专用于器械的聚合物组合物或共混物成为可能。
相对于例如非外消旋PLDL-丙交酯共混物，聚-丙交酯外消旋组合物可表现出再结晶能力的显著改进。不同聚丙交酯部分的有利外消旋物排列可例如通过将聚-D-丙交酯与共聚物聚L-丙交酯-共-TMC共混来实现，所述共聚物能形成不同聚丙交酯立体部分间的外消旋晶体，例如但不限于在扩张到所需安装直径的过程中进行膨胀时。该作用力引起无有害裂纹的结晶，导致了机械性能的提高，这也反映在模数数据相对于基质材料的基数发生正向变化。
具有共聚物的组合物的交联部分结晶似乎限于单体摩尔配比范围为约90∶10至50∶50的共聚物。实际上，以50∶50的摩尔比，该聚合物部分在空间上阻碍了结晶，而较大的比例远远更适合于交联部分结晶。基于实验诱导的结晶，向具有多种丙交酯共聚物(如TMC或εCL)浓度的不同共混物中加入为了与L-丙交酯组分外消旋排列的过量的聚(D-丙交酯)，在外消旋组合物中该共聚物的有效浓度可等于或小于40％。因此，通过交联部分结晶所形成热交联可以减少伸长或蠕动，同时保持想要的韧化结构。有利地浓的外消旋组合物提高了拉伸试验中的模数数据，从而避免使用降低共混聚合物中拉伸强度的方法。
有利的外消旋组合物实施方案提供了一种就高残留单体水平而言降解作用最小的可生物吸收聚合物，使得污染物单体残留分数不超过约0.5％或优选不超过约0.3％。在实施方案中，本发明聚合物的单体污染物的浓度低至约0.2％。
本文所述实施方案的聚合物组合物可包括一种以该组合物的重量计约70％至95％、或约70％至80％存在的基质聚合物。例如，在一个实施方案中，该聚合物制剂可包括约70重量％的聚L-丙交酯(约2.5至3IV)与聚L-丙交酯-共-TMC(70/30摩尔/摩尔)(1.4至1.6IV)。在另一个实施方案中，该聚合物制剂可包括70重量％的三嵌段聚L-丙交酯-共-PEG(99/01摩尔/摩尔)(2.5至3IV)与聚L-丙交酯-共-TMC(70/30摩尔/摩尔)(1.4至1.6IV)。此外，该聚合物组合物可包括一种占约70重量％的二嵌段聚L-丙交酯-共-PEG-MME(95/05摩尔/摩尔)(2.5至3IV)与聚L-丙交酯-共-TMC(70/30摩尔/摩尔)(1.4至1.6IV)的制剂。其它实施方案提供了一些其中在组合物中用ε-己内酯替代前述TMC的制剂。类似地，一个实施方案可提供其中可用PEG-MME替代PEG的制剂。
正如该领域所理解的，可定制本发明的聚合物组合物以适应所选定的医疗器械的多种需求。所述需求包括机械强度、弹性、柔性、弹回性以及在生理和局部解剖条件下的降解速率。一种具体组合物的其它效果涉及代谢产物的溶解度、亲水性和水吸收以及基质附着或包含的药物的任何释放率。
聚合植入物的效用可通过测量质量损失、分子量降低、机械性能的保持和/或组织反应来评估。对于支架性能来说更关键的是水解稳定性、热转化结晶度和取向。对支架性能造成不利影响的其它决定因素包括但非限于单体杂质、环状的和非环状的低聚物、结构缺陷和陈化。
由以上聚合物组合物形成的医疗器械可在挤出或成型后可为显著无定形的。所述器械可进行受控再结晶以引起结晶度的增量和机械强度增强。其它结晶可通过在器械膨胀时引入拉力而引起。所述增加的再结晶可于二次或最终制造(例如通过激光切割)之前在器械“空白处”上进行或于所述二次制造之后使用。结晶化(以及由此产生的机械性能)也可通过在进一步制造之前诱导作用力而被最大化，所述作用力的诱导通过例如“冷”拉伸聚合物管、中空纤维、板或薄膜或者单丝实现。已观察到结晶度可为该医疗器械提供更大的刚性。因此，该支架的聚合物组合物和空间复合物既具无定形部分又有次晶部分。最初半结晶的聚合物部分可通过对给定器械进行拉伸或扩张的行为来处理。然而足量的无定性聚合物特征是该聚合物器械的柔性和弹性所需的。常规单体组分包括丙交酯、乙交酯、己内酯、二噁烷酮和碳酸亚丙酯。
在一个实施方案中，由所述组合物制造的医疗器械为一种用于植入体内的支架支柱结构，例如支架。这些结构将是可卷曲的以环绕拉紧并从而固定于载体装置上。相反，相同的支架是可膨胀的而无应力裂纹或断裂。支架可生物降解的支架植入物的机械性能要求强度、弹性和柔性以在所想要的支架支柱逐渐可生物降解和吸收的整个过程中应对周围组织的波动脉冲压缩，而在植入位点处不发生位错和有害冲击。因此，从某些标准来说必须使支架聚合物内含物和结构具有这些性能。该支架应该能够通过一个热增强气囊或非热气囊而膨胀的聚合物性能。该聚合实施方案提供当通过例如气球膨胀而在膨胀时的正交应变作用下在支架支柱中定向和/或结晶的能力。因此，结晶效应提供了改善的机械性能例如周向强度，如压缩阻力、弹性反冲以及聚合物稳定性中的周向强度。该支架也可被建造成使其在生物吸收期间相对均匀地暴露于局部组织或布满并作用于聚合物结构的循环性生物活性因子以及酶。
有利地，器官空间植入物(例如心血管支架)的聚合基质的原位降解动力学速率，可足够平缓以避免组织过载、炎性反应或其它更多的不利后果。在一个实施方案中，该支架被制造成存在至少一个月。
如以下实施例所示，可将相当程度的无定形和结晶特性设计入聚合物中。由此，发现L-丙交酯聚合物产生半结晶形态学，而外消旋的聚(D，L-丙交酯)产生了无定形聚合物。聚(L-乙交酯)为半结晶。以下实施例示出了一种制备可生物吸收支架PLDL-丙交酯共混物的方法。
实施例1：
由聚(L-丙交酯)和聚(D-丙交酯)的外消旋混合物的组合物注射浇铸一个试验圆片，所述组合物中含有15重量％50∶50摩尔比的聚(L-丙交酯-共-TMC)的共聚物改性剂。压射缸温度在110℃与225℃之间，并且成型温度为50°F至82°F，以浇铸无定形圆片。注射压力设定在1300与1450psi之间，且循环时间为50秒。发现可在该聚合物中得到合适的结晶度。DSC分析证实了常规丙交酯晶体和外消旋晶体形态学的形成。
实施例2：
将该聚合物混合物共混挤入窄管中，并且可用激光在显微镜下切成支架形式，以制得一种与位于器械一端和/或中间部分处的箍状环相连的曲折支柱的笼状网筛器械。所得到的支架器械包括一个形成周缘筛网结构的一级曲折支柱，所述筛网结构包含第二曲折支柱式样，所述式样位于支架内并位于该支架末端处或接近其末端处。可制造第二曲折支柱以在植入物完全膨胀时在垂直于管形器械纵向轴的方向上形成与第一曲折支柱相比具有更小正弦曲线或更直的箍或环状形状。具有较小或较短曲折箍或曲线的膨胀的第二曲折支柱在膨胀期间被进一步拉伸。这些支柱由此可形成具有更大结晶度并因此具有更大刚性及弹性的箍，从而使得该植入物对蠕动变化或移位具有抗性。
实施例3：
聚合物组合物可由市售的颗粒材料和共聚物添加剂制备。根据想要的重量比将干的组分称量放入一个容器中，将该容器进行30分钟或直到获得均一混合物的合适旋转，随后在真空、60℃下进一步干燥8-12小时或过夜。如上所述，可将已充分混合的组分熔融共混并注射浇铸入一对匹配盘中。使得聚合物板在偏振光源下表现出合适的弹性以及无定形形态学的外观或极低的结晶度的组合物可于120-160℃的熔化温度下用40-50巴的后压力挤出，同时将其用28叶螺旋桨以40-80rpm的转速均质化。在该方法的测定阶段期间该材料的挤压熔融共混和均质化条件可包括60-100rpm的转动速度。相对温和的注射浇铸法可使用120℃-150℃的出口温度、80-300mm/s的速率、2500巴的最大注射压、3至8秒1000-2300巴的充填压力、进入铸模内时保持室温。从注射到由铸模盘排出的总循环时间可为一分钟或更短。
实施例4：
将聚(D-丙交酯)和聚(L-丙交酯-共-TMC)的干的聚合物外消旋混合物以70∶30的重量比共混并在185-225℃下用单熔融挤塑步骤进行处理，成为管状无定形可生物吸收外消旋的共混聚合物。由于过多暴露于热和剪应力下，本实施例的熔融挤塑方法使得聚合物的降解最小化。随后的试验表明了结晶的有效诱导以及外消旋晶体形态的形成。已发现所述外消旋的共聚杂化物可用来证实有效的交联部分结晶。此外，外消旋材料可制造成具有象征多形态和或多晶结构的多个转化温度。由此，已发现本实施例的聚合物支架十分柔韧而能卷曲于橡胶球形载体上，但对于组织内的展开而言，聚合物部分的强度可随着膨胀应变成比例增加。
实施例5：
在干氮气下将含有外消旋的过量聚(D-丙交酯)的干的聚(L-丙交酯)与30重量％的聚(L-丙交酯-共-TMC)共混，随后进行熔体混合并挤出，然后进行快速空气急冷。随后的再结晶和测试证实了相对于实施例4的制剂而言显著更多的外消旋物的形成以及模数的提高。
合成受几种不同因素的影响，这些因素影响适用于可移植结构的可生物吸收聚合物机械性能；所述因素例如单体选择、引发剂选择、聚合条件以及添加剂或残留物的存在。此外，决定植入物效果的聚合特性包括亲水性、结晶度、熔化和玻璃化转变温度、分子量、分子量分布、端基、序列分布(即无规的和嵌段的)、残留单体或添加剂的存在、以及转化期间的稳定性。
在一个实施方案中，药物组合物可通过例如接到聚合物活性位点或涂覆的方式被加入到聚合物中。本发明聚合物的一个实施方案将生物愈合因子或其它药物附着或加入到聚合物基质或聚合物涂层中。
在另一实施方案中，该组合物可被制造，以使其在聚合物基质中结构上包含或附着药物。所述添加剂的目的可为，例如通过使用支架，提供心血管系统或在与医疗器械聚合物接触的血管位点处的治疗。聚合物中药物的包含或附着类型可决定其由该器械释放的速率。例如，在聚合物基质中可通过多种已知方法结合该药物或其它添加剂，所述方法包括但不限于共价键、非极性键以及酯或类似的生物可逆结合方式。
可植入装置的可生物吸收聚合物支架的实施方案被认为可用于药物递送。因此如下所述，许多化合物都是可用于在植入处治疗或缓解受伤组织以及可进一步例如在整个心血管系统或其它受伤器官中治疗或缓解受伤组织的药剂。
可被加入到基质和/或注入到医疗器械中的化合物或药物组合物的实例，包括但不限于他克莫司、西罗莫司、依维莫司、依前列醇、依前列醇类似物、α-降钙素基因相关多肽(α-CGRP)、α-降钙素基因相关多肽类似物或α-降钙素基因相关多肽受体激动剂，哌唑嗪，单核细胞趋化蛋白-1(MCP-1)，免疫抑制药如雷帕霉素、抑制平滑肌细胞迁移和/或增殖的药物、抗凝血药如凝血酶抑制剂、免疫调节药如血小板因子4和CXC趋化因子，CX3CR1受体家族抑制剂，抗炎药、甾族化合物如双氢表雄甾酮(DHEA)、睾酮、雌激素如17β-雌二醇，他汀类药物如辛伐他汀和氟伐他汀，PPAR-α-配体如非诺贝特和其它降脂药物，PPAR-δ和PPAR-γ激动剂如罗格列酮，PPAR-双αγ激动剂、LBM-642、核因子如NF-kβ、胶原合成抑制剂、血管扩张药如乙酰胆碱、阿糖腺苷、5-羟色胺(5-hydroxytryptamine或serotonin)、P物质、肾上腺髓质素、促使内皮细胞生长以及分化的生长因子如碱性成纤维细胞生长因子(bFGF)、血小板源性生长因子(PDGF)、内皮细胞生长因子(EGF)、血管内皮细胞生长因子(VEGF)，蛋白酪氨酸激酶抑制剂如米哚妥林(Midostaurin)和伊马替尼(imatinib)或任何抗血管新生抑制剂化合物，抑制成熟白细胞粘附的肽或抗体、抗生素/杀菌剂以及其它物质如速激肽、神经激肽或唾液腺激肽、速激肽NK受体激动剂，PDGF受体抑制剂如MLN-518及其衍生物、丁酸及丁酸衍生物葛根黄素、纤连蛋白、红细胞生成素、达贝泊汀、丝氨酸蛋白酶-1(SERP-1)等。上述化合物和药物可被单独或者以其结合物和/或混合物的方式施用到器械的支架上。此外，聚合物附着或包含的药物物质可以共价键或离子键的方式结合到聚合部分上以及物理包埋于聚合物基质中。只要合适，该药物可以酯型交联物、微粒或胶束簇的形式存在。
在一个实施方案中，可生物吸收可植入医疗器械用含有一个或多个隔离层的可生物降解和生物可吸收涂层覆盖，其中聚合物基质含有一种或多种前述药物物质。在该实施方案中，隔离层可包括一种合适的可生物降解材料，包括但不限于，合适的可生物降解聚合物，其包括：聚酯如PLA、PGA、PLGA、PPF、PCL、PCC、TMC以及这些物质的任何共聚物；聚羧酸、包括马来酐聚合物在内的聚酐；聚原酸酯；聚氨基酸；聚环氧乙烷；polyphosphacene；聚乳酸、聚羟基乙酸，以及它们的共聚物和混合物如聚(L-乳酸)(PLLA)、聚(D，L-丙交酯)、聚(乳酸-共-羟基乙酸)、50/50(DL-丙交酯-共-乙交酯)；聚二噁烷酮；聚富马酸亚丙酯；聚羧酚酸肽(polydesipeptide)；聚己内酯以及其共聚物和混合物如聚(D，L-丙交酯-共-己内酯)和聚己内酯共-丙烯酸丁酯；聚羟基丁酸酯戊酸酯(polyhydroxybutyrate valerate)和混合物；聚碳酸酯如酪氨酸衍生的聚碳酸酯和芳基化物(arylate)、聚亚氨基碳酸酯，以及聚二甲基三甲基-碳酸酯；氰基丙烯酸酯；磷酸钙；聚葡糖胺多糖；大分子如多糖(包括透明质酸；纤维素以及羟丙基甲基纤维素；明胶；淀粉；葡聚糖；藻酸盐及它们的衍生物)、蛋白质和多肽；以及前述任意物质的混合物和共聚物。可生物降解聚合物也可为一种表面可蚀解聚合物，例如聚羟基丁酸酯及其共聚物、聚己内酯、聚酐(晶体和无定形两种)、马来酐共聚物以及磷酸锌钙。器械上聚合物支架可具有的隔离层的数目取决于患者所需疗法所要求的治疗需求量。例如，治疗时间越长，在一段时间内所需要的治疗物质越多，隔离层越多，从而适时地提供医药物质。
在另一个实施方案中，该聚合物组合物中的添加剂可以多组分医药组合物的形式存在于基质中，例如含有一种快速释放药剂以阻碍早期新内膜增生(neointimal hyperplasia)/平滑肌细胞迁移和增殖的基质，以及一种用于释放维持血管通畅的长效剂或积极的血管重塑剂的二次生物稳定基质；所述积极的血管重塑剂例如内皮型一氧化氮合酶(eNOS)、一氧化氮供体以及衍生物如阿司匹林(aspirin)或其衍生物，生成一氧化氮的水凝胶，PPAR激动剂例如PPAR-α配体，组织纤维蛋白溶酶原激活剂，他汀类药物如阿托伐他汀(atorvastatin)、红细胞生成素、达贝泊汀、丝氨酸蛋白酶-1(SERP-1)和普伐他汀(pravastatin)，甾族化合物，以及/或者抗生素。
在另一个实施方案中，提供了一种治疗血管疾病如再狭窄和动脉粥样硬化的方法，所述方法包括向需要此类医药物质的患者局部施用该物质。该方法包括将具有涂层的本发明医疗器械植入患者的血管或具有空腔的器官中，所述涂层包括一种药物组合物，该药物组合物含一种用于抑制或减缓平滑肌细胞迁移并从而抑制或减缓再狭窄的药物或物质，以及一种生物相容的、可生物降解的、可生物蚀解的、无毒的聚合物或非聚合物基质，其中该药物组合物包括一种用于延缓释放该药物的缓慢或控制释放的制剂。该医疗器械上的涂层也可包括一种配体，例如一种用于在该器械腔表面上捕捉诸如内皮细胞和/或祖细胞的细胞抗体，从而形成一种功能性内皮。
可由本发明公开内容的组合物制备的医疗器械可包括任何用于植入的医疗器械，所述用于植入的医疗器械包括但不限于支架、植入物、支架植入物、合成的血管植入物、分流器、导管等。本发明的医疗器械实施方案可提供这样一种药物递送系统，该系统的特征在于用于有效治疗组织或器官结构中移植位点上的药物或药物混合物的不同的逐步释放速率。所述器械也可在该组合物或由该组合物组成的结构中包括提高该医疗器械原位追踪能力的不透射线物质。所述不透射线物质可包括可能干扰想要的愈合过程的无毒材料。
本发明的医疗器械可在结构上成形以提供改变的能力并使其适应植入区域，以进行标准的局部组织重建。该医疗器械可由固态转化为“橡胶态”，这样可进行较之于例如不锈钢支架而言更容易的外科手术。此外，该器械的橡胶状态使得在将其从血管位置移出时血管壁遭受任何损伤的风险较小。
在本文中所公开的实施方案中，该医疗器械包括一个支架，其具有被展开入例如动脉或静脉中、并能原位膨胀、且适应血管腔，从而在损伤位点处重建血管连续性的结构。该支架形成的结构使其具有多种不同的排列，从而使得其在填充时可卷曲并在生理条件下一旦展开即可膨胀和具有柔性。如共同未决的专利申请中所解释说明的那样，可预想具有不同构造的可生物降解的聚合物支架和/或支架壁的多种实施方案。例如，该支架为管状结构，其包括可行地设计用于使得血液穿过其壁的支柱，从而使得当血液流动通过该区域时相邻组织被浸没或者与其接触。具体的支架设计取决于支架的半径大小和纵向大小。
关于支架，该聚合物的组合物可设计为能提供一种刚性、弹性和柔性的组合，从而使得该支架的原位作用引起有效的用于心血管体系的愈合和药物治疗的管腔支撑。具体而言，关于支架，可调整并选择该聚合物的组合物，从而使其提供足以抵抗波动性血管压缩力和血流速度的聚合物强度。该结构强度和弯曲强度可设计成在长达多日或几个月的聚合材料原位生物蚀解期间持续不变。该聚合物的残余强度可在经处理血管断裂之前适当测定至少足够的时间来监测并维持愈合过程正常。用于支架的组合物可被设计用于在血管位置中提供由最初刚性支撑的性质到橡胶状或“橡胶态”稠度的缓慢转变，所述稠度可维持临床功能，如防止再狭窄。该聚合物组合物可被进一步选择以提供接近以及远离涉及血管的区域的光滑聚合表面，从而使组织刺激或损伤最小化并因此不会引起临床上显著的免疫应答。可选择聚合物以使气球驱动的膨胀发生。所述可膨胀的医疗器械可包括热气球或非热气球，其中该医疗器械可具有一种在填充期间可卷曲并且可在生理条件下膨胀的而无应力裂纹的结构。有利地，可选择聚合物组合物以在施用应力时——例如在气球膨胀期间——定向和/或结晶，从而改善其机械性能。
通过仔细选择医疗器械的聚合物组合物和结构构造，可使免疫原性和炎症应答降至最低。例如，如果该器械成形为不具有突出的轮廓，则可排除或至少使聚合抗原性和结构抗原性最少，以减缓免疫应答。类似地，通过选择合适比例的合适共聚物，组成医疗器械的聚合物的降解产品对于宿主如血管壁而言，可更“友好”或者具有更小的刺激性或免疫原性。当该聚合物组合物被设计为可引发缓慢的降解动力学时，可避免移植位点处的组织过载或其它炎症应答。
本发明所进一步公开的为一种制造本发明的可生物吸收医疗器械的方法，所述方法包括：将一种含有与改性共聚物相连的聚L-丙交酯或聚D-丙交酯的基质聚合物的可结晶的组合物共混，所述改性共聚物包括嵌段共聚物或嵌段无规共聚物形式的聚L(或D)-丙交酯-共-碳酸亚丙酯或聚L(或D)-丙交酯-共-ε-己内酯，其中丙交酯链长足够长以便于发生交联部分结晶；将该聚合物组合物成型以使所述植入物结构成形；并且切割该植入物以形成所需式样。
制备本申请医疗器械的另一种方法包括：制备一种生物可降解的聚合物结构；设计所述聚合物结构以使其具有能够植入患者体内的形状；将所述结构切割成能使该器械穿过开口并使该器械卷曲的式样(如与本专利同时提交的共同未决的专利申请11/781,225中所述)。利用了膨胀至结晶箍形的第二曲折支柱的实施方案(如与本专利同时提交的共同未决的专利申请11/781,225中所述)尤其适用于确保支架植入物在器官空间中安全，因为晶体部分较缓慢地降解并被生物吸收，因此能有利地维持支架的位置和完整性，从而避免支架过早瓦解以及危险的大量破碎。
正如本领域中所公知的，上述实施方案的聚合物支架可能缺乏通过目前可获得检测设备如X-射线探测器进行检测的对比。因此，通过电子致密或X射线折射标记物对组织植入物提高对比检测是有利的。所述标记物可见于生物可降解的斑点储藏处，所述储藏处用由已知折射X射线的材料制备的不透射线组合物填充，从而在摄影图像中变得可见(图3-7)。合适的材料包括但不限于10-90％的可包埋于生物可降解部分中的不透射线化合物或微粒，特别是沉积于多个位于预形成的聚合支架支柱元件中的杯状容器中的膏状组合物形式。
不透射线化合物可选自不透X射线化合物或折射X射线化合物，例如金属颗粒或盐。合适的标记物金属可包括铁、金、胶体银、锌、镁，这些金属可以是纯的形式或者是有机化合物的形式。其它的不透射线材料为钽、钨、铂/铱或铂。不透射线标记物可用一种或多种前述生物可降解聚合物的结合剂构成，所述聚合物如PLLA、PDLA、PLGA、PEG等。为了获得标记物材料的合适混合物，一种溶剂体系包括以下物质中的两种或多种：丙酮、甲苯、甲苯、DMSO等。此外，标记物储藏处可用于选自以下类别的抗炎药：例如PPAR激动剂、甾族化合物、mTOR抑制剂、钙调磷酸酶抑制剂等。
在一个实施方案中，不透射线标记物包括被包于PLA聚合物基质中的含铁的化合物或铁颗粒，以得到这样一种膏状物质，其可被注射于或通过其它方式沉积于聚合支柱元件中所含的合适的中空容器中。将所述杯状容器制成大小在支架支柱元件的宽度内。重金属和重稀土元素可用于多种化合物如亚铁盐、有机碘物质、铋盐或钡盐等。其它可利用的实施方案可包括天然的被包裹的铁颗粒如可进一步由交联剂交联的铁蛋白。此外，铁蛋白凝胶可通过用低浓度(0.1-2％)的戊二醛交联构成。
不透射线标记物可以多种方式与聚合物联合使用并结合。例如，标记物的流体或膏状混合物可填充于注射器中并通过针尖缓慢注射入可生物降解的支架支柱内预先形成的空腔或杯状孔中。流体混合物中所含的溶剂可使标记物材料结合到空腔壁上。含不透射线标记物点的支架可在加热/真空条件下干燥。在植入后，可生物降解的结合剂可降解为由身体吸收/排出的简单分子。因此，不透射线材料将分散在首先移植处的附近区域中。
尽管参照具体实施方案已对本发明特别示出并描述，应理解，以上所公开的以及其它的特征和功能的变型、或者它们的替换物，可根据需要结合到多种其它的不同系统或应用中。同样，本文中多种可由本领域普通技术人员随后作出的目前无法预料的或意料之外的替换物、变化、变型或改进也将意欲包含于所附权利要求中。
现描述剩下的附图：
图1图示了LPLA/LPLA/TMC非外消旋混合物与仅交联部分外消旋的DPLA/LPA/TMC和具有其它外消旋结构的DPLA/LPLA/LPLA-TMC的再结晶的模数变化；
图2A和图2B分别图示了外消旋聚合物和无外消旋结构的聚合物的DSC曲线：如图所示，显示出外消旋熔化物的+外消旋物和-外消旋物的曲线明显不同。
图3A-3G图示了制造支架医疗器械的不透射线标记储存处的实施方案方法：如(a)-(d)中所示，不透射线材料可被挤入装置(g)中所含的空穴中。如截断图(e)和(f)所示，所述空穴可为一个透孔。
图4A-4C图示了具有不透射线标记物的支架的不同支架式样。如图所示，不透射线标记物可被置于支架式样上的不同位置，同时仍可用不透射线检测方法进行检测。
图5A和图5B图示了具有不透射线标记物的支架材料的平面图。如图5A和图5B所示，不透射线标记物可被排列成在成像时或使用其它检测方法时可更容易识别的结构。
图6示出了具有实施方案中所述的不透射线标记物式样的实际支架的总透视图，所述不透射线标记物式样各自位于曲折支柱的连接点处。图7示出了图6的被不透射线标记的支架的一部分的近视图。
图8示出了配置于带囊导管上的本发明支架实施方案的透视图。
图9图示了包含环结构的充分展开的可生物吸收支架，该环结构表示充分结晶的定位环或箍。
图10A和图10B图示了表明单Tg的DSC热流曲线，并且10B示出了表明双Tg的DSC热流曲线。
参照图10A，使用德州仪器(TA instrument)的Q10DSC对聚合物样品进行热转化温度分析。样品为(A)聚(L-共-DL-丙交酯)70∶30共聚物，(B)聚(L-丙交酯/聚L-丙交酯-共-ε-己内酯)以及(C)聚(L-丙交酯/聚L-丙交酯-共-TMC)。这些聚合物在Tg为30℃和50℃处存在宽转化峰，这些峰仅存在于初始运行中。后来运行的转化温度和曲线在下表中给出。
表
Figure BSA00000846946300221
参照图10B，其它聚合物样品(LPLA/TMC杂化物)通过示出双Tg的DSC进行分析。

Claims (10)

1.一种可结晶的可生物吸收聚合物组合物，包括：一种选自聚(L-丙交酯)部分和/或聚(D-丙交酯)部分以及/或者其嵌段共聚物或嵌段无规共聚物的基质聚合物。
2.权利要求1的可结晶的可生物吸收聚合物组合物，还包括一种连有改性共聚物的基质聚合物，该基质聚合物包括聚(L-丙交酯)部分和/或聚(D-丙交酯)部分；所述改性共聚物包括嵌段共聚物形式或嵌段无规共聚物形式的聚(L-丙交酯-共-碳酸亚丙酯)或聚(D-丙交酯-共-碳酸亚丙酯)和(L-丙交酯-共-ε-己内酯)或聚(D-丙交酯-共-ε-己内酯)，其中丙交酯链长度足以使得进行交联部分结晶。
3.权利要求1的可结晶的可生物吸收聚合物组合物，其中该聚合物组合物熔体在聚L和聚D丙交酯部分之间形成丙交酯外消旋物立体复合物晶体结构。
4.权利要求1的可结晶的可生物吸收聚合物组合物，其中该聚合物组合物熔体通过以下部分形成丙交酯外消旋物立体复合物晶体结构，所述部分包括：
连有聚(L-丙交酯-共-碳酸亚丙酯)或聚(L-丙交酯-共-ε-己内酯)的聚L-丙交酯与聚D-丙交酯；
连有聚(L-丙交酯-共-碳酸亚丙酯)或聚(L-丙交酯-共-ε-己内酯)的聚D-丙交酯；
连有聚(D-丙交酯-共-碳酸亚丙酯)或聚(L-丙交酯-共-ε-己内酯)的聚L-丙交酯；
连有聚(D-丙交酯-共-碳酸亚丙酯)或聚(L-丙交酯-共-ε-己内酯)的聚L-丙交酯与聚D-丙交酯；
连有(聚D-丙交酯-共-碳酸亚丙酯)或聚(L-丙交酯-共-ε-己内酯)的聚L-丙交酯-共-PEG；以及
连有聚(L-丙交酯-共-碳酸亚丙酯)或聚(L-丙交酯-共-ε-己内酯)的聚D-丙交酯-共-PEG。
5.权利要求1的可结晶的可生物吸收聚合物组合物，其中所述基质聚合物以重量计占该组合物的约70％至约85％、或约70％至约80％。
6.权利要求1的可结晶的可生物吸收聚合物组合物，其中所述基质聚合物的70重量％为聚L-丙交酯且30重量％为改性共聚物聚L-丙交酯-共-TMC。
7.权利要求1的可结晶的可生物吸收聚合物组合物，其中所述改性共聚物不高于该组合物的约40％。
8.权利要求1的可结晶的可生物吸收聚合物组合物，其中该组合物的残留单体浓度小于0.5％或优选小于0.3％。
9.一种可生物吸收的支架聚合物，包括一种可结晶的组合物，该组合物包括一种连有改性共聚物的聚L-丙交酯或聚D-丙交酯的基质聚合物；所述改性共聚物包括嵌段共聚物形式或嵌段无规共聚物形式的聚L(或D)-丙交酯-共-碳酸亚丙酯或聚L(或D)-丙交酯-共-ε-己内酯，其中丙交酯链长度足以进行交联部分结晶。
10.权利要求9的可生物吸收的支架聚合物，其中所述基质聚合物以重量计占该组合物的约60％至约90％、或约70％至约80％。
CN201310025670.4A 2006-07-20 2007-07-20 用于医疗器械的可生物吸收聚合物组合物 Active CN103122132B (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US80793206P 2006-07-20 2006-07-20
US60/807,932 2006-07-20
US86243306P 2006-10-20 2006-10-20
US60/862,433 2006-10-20
CN2007800347513A CN101522754B (zh) 2006-07-20 2007-07-20 用于医疗器械的可生物吸收聚合物组合物

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
CN2007800347513A Division CN101522754B (zh) 2006-07-20 2007-07-20 用于医疗器械的可生物吸收聚合物组合物

Publications (2)

Publication Number Publication Date
CN103122132A true CN103122132A (zh) 2013-05-29
CN103122132B CN103122132B (zh) 2016-03-16

Family

ID=38957678

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201310025670.4A Active CN103122132B (zh) 2006-07-20 2007-07-20 用于医疗器械的可生物吸收聚合物组合物

Country Status (5)

Country Link
US (15) US7846361B2 (zh)
EP (4) EP3009477B1 (zh)
CN (1) CN103122132B (zh)
HK (1) HK1222667A1 (zh)
WO (1) WO2008011615A2 (zh)

Families Citing this family (66)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030229393A1 (en) * 2001-03-15 2003-12-11 Kutryk Michael J. B. Medical device with coating that promotes cell adherence and differentiation
US20070156230A1 (en) 2006-01-04 2007-07-05 Dugan Stephen R Stents with radiopaque markers
US8752268B2 (en) 2006-05-26 2014-06-17 Abbott Cardiovascular Systems Inc. Method of making stents with radiopaque markers
US8460364B2 (en) * 2006-07-20 2013-06-11 Orbusneich Medical, Inc. Bioabsorbable polymeric medical device
EP3009477B1 (en) 2006-07-20 2024-01-24 Orbusneich Medical Pte. Ltd Bioabsorbable polymeric composition for a medical device
WO2008011612A2 (en) * 2006-07-20 2008-01-24 Orbusneich Medical, Inc. Bioabsorbable polymeric medical device
EP2073754A4 (en) * 2006-10-20 2012-09-26 Orbusneich Medical Inc BIOABSORBABLE POLYMER COMPOSITION AND MEDICAL DEVICE BACKGROUND
US7959942B2 (en) * 2006-10-20 2011-06-14 Orbusneich Medical, Inc. Bioabsorbable medical device with coating
US20110130822A1 (en) * 2007-07-20 2011-06-02 Orbusneich Medical, Inc. Bioabsorbable Polymeric Compositions and Medical Devices
US8647292B2 (en) * 2007-08-17 2014-02-11 The Invention Science Fund I, Llc Systems, devices, and methods including catheters having components that are actively controllable between two or more wettability states
US20090177254A1 (en) * 2007-08-17 2009-07-09 Searete Llc, A Limited Liability Of The State Of The State Of Delaware System, devices, and methods including actively-controllable electrostatic and electromagnetic sterilizing excitation delivery system
US8753304B2 (en) * 2007-08-17 2014-06-17 The Invention Science Fund I, Llc Systems, devices, and methods including catheters having acoustically actuatable waveguide components for delivering a sterilizing stimulus to a region proximate a surface of the catheter
US8734718B2 (en) * 2007-08-17 2014-05-27 The Invention Science Fund I, Llc Systems, devices, and methods including catheters having an actively controllable therapeutic agent delivery component
US8162924B2 (en) * 2007-08-17 2012-04-24 The Invention Science Fund I, Llc System, devices, and methods including actively-controllable superoxide water generating systems
US9005263B2 (en) 2007-08-17 2015-04-14 The Invention Science Fund I, Llc System, devices, and methods including actively-controllable sterilizing excitation delivery implants
US8366652B2 (en) * 2007-08-17 2013-02-05 The Invention Science Fund I, Llc Systems, devices, and methods including infection-fighting and monitoring shunts
US20090163964A1 (en) * 2007-08-17 2009-06-25 Searete Llc, A Limited Liability Corporation Of The State Of Delaware System, devices, and methods including sterilizing excitation delivery implants with general controllers and onboard power
US20090163977A1 (en) * 2007-08-17 2009-06-25 Searete Llc, A Limited Liability Corporation Of The State Of Delaware System, devices, and methods including sterilizing excitation delivery implants with cryptographic logic components
US20090048648A1 (en) * 2007-08-17 2009-02-19 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Self-sterilizing device
US8702640B2 (en) * 2007-08-17 2014-04-22 The Invention Science Fund I, Llc System, devices, and methods including catheters configured to monitor and inhibit biofilm formation
US8460229B2 (en) 2007-08-17 2013-06-11 The Invention Science Fund I, Llc Systems, devices, and methods including catheters having components that are actively controllable between transmissive and reflective states
US8706211B2 (en) 2007-08-17 2014-04-22 The Invention Science Fund I, Llc Systems, devices, and methods including catheters having self-cleaning surfaces
WO2009050265A1 (en) 2007-10-17 2009-04-23 Angiomed Gmbh & Co. Medizintechnik Kg Delivery system for a self-expanding device for placement in a bodily lumen
US8414638B2 (en) * 2008-03-12 2013-04-09 Abbott Cardiovascular Systems Inc. Method for fabricating a polymer stent with break-away links for enhanced stent retenton
CN102014806B (zh) * 2008-05-09 2013-10-30 安吉奥米德医药技术有限责任两合公司 将扩张件置入套管中的方法
GB0815339D0 (en) * 2008-08-21 2008-10-01 Angiomed Ag Method of loading a stent into a sheath
US8372332B2 (en) * 2008-08-11 2013-02-12 Abbott Cardiovascular Systems Inc. Fabricating an implantable medical device from an amorphous or very low crystallinity polymer construct
WO2010042854A1 (en) * 2008-10-10 2010-04-15 Orbusneich Medical, Inc. Bioabsorbable polymeric medical device
WO2010042952A1 (en) * 2008-10-11 2010-04-15 Orbusneich Medical, Inc. Bioabsorbable polymeric compositions and medical devices
US20110295088A1 (en) 2008-12-04 2011-12-01 Searete Llc, A Limited Liability Corporation Of The State Of Delaware Systems, devices, and methods including implantable devices with anti-microbial properties
US8585627B2 (en) * 2008-12-04 2013-11-19 The Invention Science Fund I, Llc Systems, devices, and methods including catheters configured to monitor biofilm formation having biofilm spectral information configured as a data structure
GB0823716D0 (en) 2008-12-31 2009-02-04 Angiomed Ag Stent delivery device with rolling stent retaining sheath
WO2010132899A1 (en) * 2009-05-15 2010-11-18 Orbusneich Medical, Inc. Bioabsorbable polymeric compositions and medical devices
US9265633B2 (en) * 2009-05-20 2016-02-23 480 Biomedical, Inc. Drug-eluting medical implants
WO2011007352A2 (en) * 2009-07-13 2011-01-20 Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. Intraluminal polymeric devices for the treatment of aneurysms
US8119704B2 (en) * 2009-07-21 2012-02-21 Abbott Cardiovascular Systems Inc. Implantable medical device comprising copolymer of L-lactide with improved fracture toughness
US8889823B2 (en) * 2009-07-21 2014-11-18 Abbott Cardiovascular Systems Inc. Method to make poly(L-lactide) stent with tunable degradation rate
US9889238B2 (en) 2009-07-21 2018-02-13 Abbott Cardiovascular Systems Inc. Biodegradable stent with adjustable degradation rate
GB0921240D0 (en) * 2009-12-03 2010-01-20 Angiomed Ag Stent device delivery system and method of making such
GB0921238D0 (en) * 2009-12-03 2010-01-20 Angiomed Ag Stent device delivery system and method of making such
GB0921236D0 (en) * 2009-12-03 2010-01-20 Angiomed Ag Stent device delivery system and method of making such
GB0921237D0 (en) * 2009-12-03 2010-01-20 Angiomed Ag Stent device delivery system and method of making such
US8562670B2 (en) * 2010-04-01 2013-10-22 Abbott Cardiovascular Systems Inc. Implantable prosthesis with depot retention feature
US9173978B2 (en) 2010-09-22 2015-11-03 Ethicon, Inc. Bioabsorbable polymeric compositions, processing methods, and medical devices therefrom
US8501875B2 (en) 2010-10-28 2013-08-06 Covidien Lp Surface induced ring-opening polymerization and medical devices formed therefrom
GB201020373D0 (en) 2010-12-01 2011-01-12 Angiomed Ag Device to release a self-expanding implant
US8709466B2 (en) 2011-03-31 2014-04-29 International Business Machines Corporation Cationic polymers for antimicrobial applications and delivery of bioactive materials
US8642086B2 (en) 2011-03-31 2014-02-04 International Business Machines Corporation Antimicrobial compositions, methods of preparation thereof, and uses thereof
JP2014512438A (ja) 2011-04-25 2014-05-22 サン−ゴバン パフォーマンス プラスティックス コーポレイション ブレンド組成物、可撓性管材、およびそのブレンド物の製造方法
US8487017B2 (en) * 2011-06-27 2013-07-16 Covidien Lp Biodegradable materials for orthopedic devices based on polymer stereocomplexes
KR101316069B1 (ko) 2011-08-25 2013-10-11 한국과학기술연구원 유연한 폴리락티드 입체이성질 복합체의 제조방법 및 이의 방법에 의해 제조된 화합물
AU2012321050A1 (en) * 2011-10-04 2014-04-17 Smartstent Pty Ltd Sensing or stimulating activity of tissue
US9101678B2 (en) 2011-11-03 2015-08-11 Elwha Llc Heat-sanitization of surfaces
US20140178456A1 (en) * 2012-08-30 2014-06-26 Udaya Sankar Devanaboyina Methods and compositions for treating type 2 diabetes and related conditions
GB2512016A (en) 2012-09-24 2014-09-24 Arterius Ltd Methods
US10441236B2 (en) * 2012-10-19 2019-10-15 Biosense Webster (Israel) Ltd. Integration between 3D maps and fluoroscopic images
US10518003B2 (en) * 2014-07-07 2019-12-31 Meril Life Sciences Pvt. Ltd. Method to manufacture thin strut stent from bioabsorbable polymer with high fatigue and radial strength
US9999527B2 (en) 2015-02-11 2018-06-19 Abbott Cardiovascular Systems Inc. Scaffolds having radiopaque markers
US9700443B2 (en) 2015-06-12 2017-07-11 Abbott Cardiovascular Systems Inc. Methods for attaching a radiopaque marker to a scaffold
JP6598152B2 (ja) * 2015-09-18 2019-10-30 テルモ株式会社 ステント
AU2016341230B2 (en) 2015-10-20 2020-01-16 The University Of Melbourne Medical device for sensing and or stimulating tissue
RU2753447C2 (ru) * 2016-10-04 2021-08-16 Ясухиро СЁБАЯСИ Гибкий стент
AU2017387027B2 (en) 2016-12-29 2020-04-23 Boston Scientific Scimed, Inc. Medical devices formed from polymer filaments
WO2018195083A1 (en) 2017-04-18 2018-10-25 The University Of Melbourne Endovascular device for sensing and or stimulating tissue
CN112118812A (zh) 2018-03-29 2020-12-22 萨哈詹德医疗技术私人有限公司 支架
US20210017329A1 (en) * 2019-07-19 2021-01-21 Evonik Operations Gmbh Multi-block shape memory bioresorbable polymers

Family Cites Families (343)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4057537A (en) 1975-01-28 1977-11-08 Gulf Oil Corporation Copolymers of L-(-)-lactide and epsilon caprolactone
US4300565A (en) 1977-05-23 1981-11-17 American Cyanamid Company Synthetic polyester surgical articles
US4243775A (en) 1978-11-13 1981-01-06 American Cyanamid Company Synthetic polyester surgical articles
US4379138A (en) * 1981-12-28 1983-04-05 Research Triangle Institute Biodegradable polymers of lactones
US4655777A (en) 1983-12-19 1987-04-07 Southern Research Institute Method of producing biodegradable prosthesis and products therefrom
US4650488A (en) 1984-05-16 1987-03-17 Richards Medical Company Biodegradable prosthetic device
US4944974A (en) 1984-10-24 1990-07-31 Zachariades Anagnostis E Composite structures of ultra-high-molecular-weight polymers, such as ultra-high-molecular-weight polyethylene products, and method of producing such structures
US4719246A (en) 1986-12-22 1988-01-12 E. I. Du Pont De Nemours And Company Polylactide compositions
FI81498C (fi) 1987-01-13 1990-11-12 Biocon Oy Kirurgiska material och instrument.
DE3708916A1 (de) 1987-03-19 1988-09-29 Boehringer Ingelheim Kg Verfahren zur reinigung resorbierbarer polyester
US5185408A (en) 1987-12-17 1993-02-09 Allied-Signal Inc. Medical devices fabricated totally or in part from copolymers of recurring units derived from cyclic carbonates and lactides
US4916193A (en) 1987-12-17 1990-04-10 Allied-Signal Inc. Medical devices fabricated totally or in part from copolymers of recurring units derived from cyclic carbonates and lactides
US5120802A (en) 1987-12-17 1992-06-09 Allied-Signal Inc. Polycarbonate-based block copolymers and devices
US5256764A (en) 1987-12-17 1993-10-26 United States Surgical Corporation Medical devices fabricated from homopolymers and copolymers having recurring carbonate units
US5066772A (en) 1987-12-17 1991-11-19 Allied-Signal Inc. Medical devices fabricated totally or in part from copolymers of recurring units derived from cyclic carbonates and lactides
US5274074A (en) 1987-12-17 1993-12-28 United States Surgical Corporation Medical devices fabricated from homopolymers and copolymers having recurring carbonate units
US5145945A (en) 1987-12-17 1992-09-08 Allied-Signal Inc. Homopolymers and copolymers having recurring carbonate units
US5502158A (en) 1988-08-08 1996-03-26 Ecopol, Llc Degradable polymer composition
US6740731B2 (en) 1988-08-08 2004-05-25 Cargill Dow Polymers Llc Degradation control of environmentally degradable disposable materials
US4938763B1 (en) 1988-10-03 1995-07-04 Atrix Lab Inc Biodegradable in-situ forming implants and method of producing the same
US5085629A (en) 1988-10-06 1992-02-04 Medical Engineering Corporation Biodegradable stent
US6171338B1 (en) 1988-11-10 2001-01-09 Biocon, Oy Biodegradable surgical implants and devices
FI85223C (fi) 1988-11-10 1992-03-25 Biocon Oy Biodegraderande kirurgiska implant och medel.
DK0401844T3 (da) 1989-06-09 1996-02-19 Aesculap Ag Resorberbare formlegemer og fremgangsmåde til fremstilling heraf
US5290494A (en) 1990-03-05 1994-03-01 Board Of Regents, The University Of Texas System Process of making a resorbable implantation device
NL9000959A (nl) 1990-04-21 1991-11-18 Stamicarbon Katalysator voor de polymerisatie van cyclische esters.
US5097005A (en) 1990-05-11 1992-03-17 E. I. Du Pont De Nemours And Company Novel copolyesters and their use in compostable products such as disposable diapers
US5342395A (en) 1990-07-06 1994-08-30 American Cyanamid Co. Absorbable surgical repair devices
NL9001641A (nl) 1990-07-19 1992-02-17 Stamicarbon Werkwijze voor het maken van polymere producten van cyclische esters.
NL9001984A (nl) 1990-09-10 1992-04-01 Stamicarbon Werkwijze voor het produceren van een voorwerp van een copolymeer van lactide en epsilon-caprolacton voor medische toepassingen.
US5320624A (en) * 1991-02-12 1994-06-14 United States Surgical Corporation Blends of glycolide and/or lactide polymers and caprolactone and/or trimethylene carbonate polymers and absorbable surgical devices made therefrom
SE9100610D0 (sv) 1991-03-04 1991-03-04 Procordia Ortech Ab Bioresorbable material for medical use
US5500013A (en) 1991-10-04 1996-03-19 Scimed Life Systems, Inc. Biodegradable drug delivery vascular stent
US5302397A (en) 1991-11-19 1994-04-12 Amsden Brian G Polymer-based drug delivery system
NL9102148A (nl) 1991-12-20 1993-07-16 Dsm Nv Copolymeer van lacton en carbonaat en werkwijze voor het verkrijgen ervan.
US5225521A (en) 1991-12-31 1993-07-06 E. I. Du Pont De Nemours And Company Star-shaped hydroxyacid polymers
US5142023A (en) 1992-01-24 1992-08-25 Cargill, Incorporated Continuous process for manufacture of lactide polymers with controlled optical purity
US5338822A (en) 1992-10-02 1994-08-16 Cargill, Incorporated Melt-stable lactide polymer composition and process for manufacture thereof
US5322925A (en) * 1992-10-30 1994-06-21 United States Surgical Corporation Absorbable block copolymers and surgical articles made therefrom
NL9201949A (nl) 1992-11-06 1994-06-01 Univ Groningen Met rubber gemodificeerde polylactide-samenstelling.
DE4239781A1 (de) 1992-11-26 1994-06-01 Basf Ag Formkörper aus geschäumten Polylactiden und Verfahren zu ihrer Herstellung
US5317064A (en) 1992-12-11 1994-05-31 E. I. Du Pont De Nemours And Company Manufacture of polylactide stereocomplexes
US6221958B1 (en) 1993-01-06 2001-04-24 Societe De Conseils De Recherches Et D'applications Scientifiques, Sas Ionic molecular conjugates of biodegradable polyesters and bioactive polypeptides
US5565215A (en) 1993-07-23 1996-10-15 Massachusettes Institute Of Technology Biodegradable injectable particles for imaging
GB2281865B (en) 1993-09-16 1997-07-30 Cordis Corp Endoprosthesis having multiple laser welded junctions,method and procedure
US6551618B2 (en) 1994-03-15 2003-04-22 University Of Birmingham Compositions and methods for delivery of agents for neuronal regeneration and survival
NL9400519A (nl) 1994-03-31 1995-11-01 Rijksuniversiteit Intravasculaire polymere stent.
US20020032488A1 (en) 1994-05-13 2002-03-14 Brekke John H. Device for regeneration of articular cartilage and other tissue
ATE196486T1 (de) 1994-08-10 2000-10-15 Peter Neuenschwander Biokompatibles blockcopolymer
JP3379841B2 (ja) 1994-10-28 2003-02-24 高砂香料工業株式会社 ブロック共重合ポリ（エステル−カーボネート）及びその製造方法
US7001328B1 (en) 1994-11-15 2006-02-21 Kenton W. Gregory Method for using tropoelastin and for producing tropoelastin biomaterials
AU3783295A (en) 1994-11-16 1996-05-23 Advanced Cardiovascular Systems Inc. Shape memory locking mechanism for intravascular stent
AU4402396A (en) 1994-12-21 1996-07-10 Universiteit Twente Catalytic ring opening polymerization of lactones, carbonates, ethers, morpholine-2,5-diones and anhydrides and catalyst therefor
US7204848B1 (en) 1995-03-01 2007-04-17 Boston Scientific Scimed, Inc. Longitudinally flexible expandable stent
US6413539B1 (en) 1996-10-31 2002-07-02 Poly-Med, Inc. Hydrogel-forming, self-solvating absorbable polyester copolymers, and methods for use thereof
US5691424A (en) 1995-05-25 1997-11-25 Mitsui Toatsu Chemicals, Inc. Heat-resistant molded article of lactic acid-base polymer
GB9514285D0 (en) 1995-07-13 1995-09-13 Univ Nottingham Polymeric lamellar substrate particles for drug delivery
US6107453A (en) 1995-07-28 2000-08-22 Sanitaria Scaligera S.P.A. Process of surface activation of biocompatible and bioabsorbable aliphatic polyesters and polyesters thus activated
IT1277799B1 (it) 1995-07-28 1997-11-12 Sanitaria Scaligera Spa Procedimento di funzionalizzazione superficiale di poliesteri- alifatici biocompatibili e bioassorbibili e poliesteri cosi' attivati
JPH11510837A (ja) 1995-07-28 1999-09-21 フォーカル，インコーポレイテッド 薬物送達のための制御された放出薬剤および組織処置薬剤としての使用のためのマルチブロック生分解性ヒドロゲル
FI98136C (fi) 1995-09-27 1997-04-25 Biocon Oy Kudosolosuhteissa hajoava materiaali ja menetelmä sen valmistamiseksi
FI954565A0 (fi) 1995-09-27 1995-09-27 Biocon Oy Biolgiskt upploeslig av ett polymerbaserat material tillverkad implant och foerfarande foer dess tillverkning
US5849374A (en) 1995-09-28 1998-12-15 Cargill, Incorporated Compostable multilayer structures, methods for manufacture, and articles prepared therefrom
US5849401A (en) 1995-09-28 1998-12-15 Cargill, Incorporated Compostable multilayer structures, methods for manufacture, and articles prepared therefrom
US20010051833A1 (en) 1995-10-11 2001-12-13 Walter Mary Ann Moldable, hand-shapable biodegradable implant material
US5776161A (en) 1995-10-16 1998-07-07 Instent, Inc. Medical stents, apparatus and method for making same
US5702717A (en) 1995-10-25 1997-12-30 Macromed, Inc. Thermosensitive biodegradable polymers based on poly(ether-ester)block copolymers
US5665428A (en) 1995-10-25 1997-09-09 Macromed, Inc. Preparation of peptide containing biodegradable microspheres by melt process
IT1278868B1 (it) 1995-10-27 1997-11-28 Sanitaria Scaligera Spa Metodo per l'ottenimento di un materiale riassorbibile atto ad essere utilizzato come elemento di rivestimento per la prevenzione di
DE19545257A1 (de) 1995-11-24 1997-06-19 Schering Ag Verfahren zur Herstellung von morphologisch einheitlichen Mikrokapseln sowie nach diesem Verfahren hergestellte Mikrokapseln
US5670161A (en) 1996-05-28 1997-09-23 Healy; Kevin E. Biodegradable stent
US6143037A (en) 1996-06-12 2000-11-07 The Regents Of The University Of Michigan Compositions and methods for coating medical devices
US6264970B1 (en) 1996-06-26 2001-07-24 Takeda Chemical Industries, Ltd. Sustained-release preparation
US5916950A (en) 1996-07-26 1999-06-29 Mitsui Chemicals, Inc. Resin composition and molded articles thereof
US5925061A (en) 1997-01-13 1999-07-20 Gore Enterprise Holdings, Inc. Low profile vascular stent
UA54505C2 (uk) 1997-04-03 2003-03-17 Гілфорд Фармасьютікалз Інк. Полімери, що біологічно розкладаються, зшиті фосфатами, композиції, вироби і способи для їх виготовлення і використання
US10028851B2 (en) 1997-04-15 2018-07-24 Advanced Cardiovascular Systems, Inc. Coatings for controlling erosion of a substrate of an implantable medical device
US6033433A (en) 1997-04-25 2000-03-07 Scimed Life Systems, Inc. Stent configurations including spirals
EP0884029B1 (en) 1997-06-13 2004-12-22 Gary J. Becker Expandable intraluminal endoprosthesis
FI972890A (fi) 1997-07-08 1999-01-09 Bioxid Oy Uusi muovipohjainen komposiitti ja sen käytt¦
US6174330B1 (en) * 1997-08-01 2001-01-16 Schneider (Usa) Inc Bioabsorbable marker having radiopaque constituents
US6245103B1 (en) 1997-08-01 2001-06-12 Schneider (Usa) Inc Bioabsorbable self-expanding stent
GB9717433D0 (en) 1997-08-19 1997-10-22 Univ Nottingham Biodegradable composites
JP2001514279A (ja) 1997-08-25 2001-09-11 ユニオン・カーバイド・ケミカルズ・アンド・プラスティックス・テクノロジー・コーポレイション 生分解性ラクトン共重合体
US5948016A (en) 1997-09-25 1999-09-07 Jang; G. David Intravascular stent with non-parallel slots
US6165217A (en) 1997-10-02 2000-12-26 Gore Enterprise Holdings, Inc. Self-cohering, continuous filament non-woven webs
US6110164A (en) 1997-12-05 2000-08-29 Intratherapeutics, Inc. Guideless catheter segment
US6033394A (en) 1997-12-05 2000-03-07 Intratherapeutics, Inc. Catheter support structure
US5964798A (en) 1997-12-16 1999-10-12 Cardiovasc, Inc. Stent having high radial strength
US6511748B1 (en) 1998-01-06 2003-01-28 Aderans Research Institute, Inc. Bioabsorbable fibers and reinforced composites produced therefrom
US20020011167A1 (en) * 1998-01-15 2002-01-31 Murray Figov Plateless printing system
US7070607B2 (en) 1998-01-27 2006-07-04 The Regents Of The University Of California Bioabsorbable polymeric implants and a method of using the same to create occlusions
US6623521B2 (en) 1998-02-17 2003-09-23 Md3, Inc. Expandable stent with sliding and locking radial elements
US6558415B2 (en) 1998-03-27 2003-05-06 Intratherapeutics, Inc. Stent
JP4583597B2 (ja) 1998-05-05 2010-11-17 ボストン サイエンティフィック リミテッド 末端が滑らかなステント
US6297349B1 (en) 1998-08-25 2001-10-02 Union Carbide Chemicals & Plastics Technology Corporation Condensation copolymers having supressed crystallinity
US6921811B2 (en) 1998-09-22 2005-07-26 Biosurface Engineering Technologies, Inc. Bioactive coating composition and methods
US6537284B1 (en) 1998-10-29 2003-03-25 Kanji Inoue Device for guiding an appliance
US6255408B1 (en) 1998-11-06 2001-07-03 Poly-Med, Inc. Copolyesters with minimized hydrolytic instability and crystalline absorbable copolymers thereof
US6625134B1 (en) * 1998-11-09 2003-09-23 Samsung Electronics Co., Ltd. System and method for reallocating a traffic channel in soft handoff state
US6350464B1 (en) 1999-01-11 2002-02-26 Guilford Pharmaceuticals, Inc. Methods for treating ovarian cancer, poly (phosphoester) compositions, and biodegradable articles for same
US6365173B1 (en) 1999-01-14 2002-04-02 Efrat Biopolymers Ltd. Stereocomplex polymeric carriers for drug delivery
JP4548623B2 (ja) 1999-02-24 2010-09-22 多木化学株式会社 生体材料
US6251134B1 (en) 1999-02-28 2001-06-26 Inflow Dynamics Inc. Stent with high longitudinal flexibility
US6206883B1 (en) 1999-03-05 2001-03-27 Stryker Technologies Corporation Bioabsorbable materials and medical devices made therefrom
US6537585B1 (en) 1999-03-26 2003-03-25 Guilford Pharmaceuticals, Inc. Methods and compositions for treating solid tumors
US6730116B1 (en) 1999-04-16 2004-05-04 Medtronic, Inc. Medical device for intraluminal endovascular stenting
US6273911B1 (en) 1999-04-22 2001-08-14 Advanced Cardiovascular Systems, Inc. Variable strength stent
US6368346B1 (en) 1999-06-03 2002-04-09 American Medical Systems, Inc. Bioresorbable stent
FR2795438B1 (fr) 1999-06-28 2001-08-03 Dumez Gtm Structure de pont ou de passerelle mixte beton-acier, en particulier de pont a tablier bipoutre mixte sous chaussee
AU782297B2 (en) 1999-06-30 2005-07-14 Ethicon Inc. Porous tissue scaffoldings for the repair or regeneration of tissue
US6306424B1 (en) 1999-06-30 2001-10-23 Ethicon, Inc. Foam composite for the repair or regeneration of tissue
US6355699B1 (en) 1999-06-30 2002-03-12 Ethicon, Inc. Process for manufacturing biomedical foams
US6333029B1 (en) 1999-06-30 2001-12-25 Ethicon, Inc. Porous tissue scaffoldings for the repair of regeneration of tissue
US6709427B1 (en) 1999-08-05 2004-03-23 Kensey Nash Corporation Systems and methods for delivering agents into targeted tissue of a living being
US6352667B1 (en) 1999-08-24 2002-03-05 Absorbable Polymer Technologies, Inc. Method of making biodegradable polymeric implants
US20030144570A1 (en) 1999-11-12 2003-07-31 Angiotech Pharmaceuticals, Inc. Compositions and methods for treating disease utilizing a combination of radioactive therapy and cell-cycle inhibitors
AU1939801A (en) 1999-12-01 2001-06-12 Selective Genetics, Inc. In situ bioreactors and methods of use thereof
WO2001042333A2 (en) 1999-12-13 2001-06-14 Michigan State University Process for the preparation of polymers of dimeric cyclic esters
US6338739B1 (en) 1999-12-22 2002-01-15 Ethicon, Inc. Biodegradable stent
US6740100B2 (en) 1999-12-23 2004-05-25 Omeros Corporation Tendon repair using adhesive
US6312458B1 (en) 2000-01-19 2001-11-06 Scimed Life Systems, Inc. Tubular structure/stent/stent securement member
US6575888B2 (en) 2000-01-25 2003-06-10 Biosurface Engineering Technologies, Inc. Bioabsorbable brachytherapy device
WO2001068052A2 (en) 2000-03-10 2001-09-20 Johns Hopkins University Phosphate based biodegradable polymers
US7592017B2 (en) 2000-03-10 2009-09-22 Mast Biosurgery Ag Resorbable thin membranes
US20030229393A1 (en) 2001-03-15 2003-12-11 Kutryk Michael J. B. Medical device with coating that promotes cell adherence and differentiation
US8088060B2 (en) 2000-03-15 2012-01-03 Orbusneich Medical, Inc. Progenitor endothelial cell capturing with a drug eluting implantable medical device
US8460367B2 (en) 2000-03-15 2013-06-11 Orbusneich Medical, Inc. Progenitor endothelial cell capturing with a drug eluting implantable medical device
US20050271701A1 (en) 2000-03-15 2005-12-08 Orbus Medical Technologies, Inc. Progenitor endothelial cell capturing with a drug eluting implantable medical device
US20160287708A9 (en) 2000-03-15 2016-10-06 Orbusneich Medical, Inc. Progenitor Endothelial Cell Capturing with a Drug Eluting Implantable Medical Device
US20070141107A1 (en) 2000-03-15 2007-06-21 Orbusneich Medical, Inc. Progenitor Endothelial Cell Capturing with a Drug Eluting Implantable Medical Device
DE60007070D1 (de) 2000-03-31 2004-01-22 Polyganics Bv Biomedizinisches Polyurethanamid, seine Herstellung und Verwendung
GB0011356D0 (en) 2000-05-12 2000-06-28 Univ Nottingham Trent Medical implant materials
WO2001087575A2 (en) 2000-05-12 2001-11-22 The Regents Of The University Of Michigan Reverse fabrication of porous materials
JP2003533276A (ja) 2000-05-16 2003-11-11 レンセラール ポリテクニック インスティチュート 生物医学的適用のための電気伝導性ナノ複合材料
WO2001095834A1 (en) 2000-06-13 2001-12-20 Scimed Life Systems, Inc. Disintegrating stent and method of making same
US6652579B1 (en) 2000-06-22 2003-11-25 Advanced Cardiovascular Systems, Inc. Radiopaque stent
IL137090A (en) 2000-06-29 2010-04-15 Pentech Medical Devices Ltd Polymeric stent
US6455665B1 (en) 2000-07-06 2002-09-24 Guilford Pharmaceuticals Inc. Polymers and polymerization processes
EP1301197A2 (en) 2000-07-21 2003-04-16 The Board Of Regents, The University Of Texas System Device providing regulated growth factor delivery for the regeneration of peripheral nerves
DE10036288A1 (de) * 2000-07-26 2002-02-07 Bosch Gmbh Robert Unipolar-Transversalflußmaschine
EP1313422B1 (en) 2000-08-24 2010-01-20 Sidney Lerner Non-hormonal vaginal contraceptive
US6254632B1 (en) 2000-09-28 2001-07-03 Advanced Cardiovascular Systems, Inc. Implantable medical device having protruding surface structures for drug delivery and cover attachment
WO2002031037A1 (en) 2000-10-11 2002-04-18 Union Carbide Chemicals & Plastics Technology Corporation Compositions comprising crystalline condensation polymers and nucleating agents
EP1208754A1 (en) 2000-11-21 2002-05-29 Givaudan SA Particulate material
SG125885A1 (en) 2000-12-05 2006-10-30 Univ Singapore A polymer and nerve guide conduits formed thereof
US20020106406A1 (en) 2000-12-08 2002-08-08 Mchugh Anthony J. Crystallizable/non-crystallizable polymer composites
US20030049320A1 (en) 2000-12-18 2003-03-13 Wockhardt Limited Novel in-situ forming controlled release microcarrier delivery system
ATE361057T1 (de) 2000-12-21 2007-05-15 Alrise Biosystems Gmbh Verfahren umfassend einen induzierten phasenübergang zur herstellung von hydrophobe wirkstoffe enthaltenden mikropartikeln
DE10064108A1 (de) 2000-12-21 2002-07-18 Siemens Production & Logistics Bestückkopf und Bestücksystem für eine Bestückvorrichtung zum Bestücken von Bauelementen
US20040220660A1 (en) 2001-02-05 2004-11-04 Shanley John F. Bioresorbable stent with beneficial agent reservoirs
US6540777B2 (en) 2001-02-15 2003-04-01 Scimed Life Systems, Inc. Locking stent
US6949251B2 (en) 2001-03-02 2005-09-27 Stryker Corporation Porous β-tricalcium phosphate granules for regeneration of bone tissue
DE10113302B4 (de) 2001-03-19 2009-09-24 Fraunhofer-Gesellschaft für die angewandte Forschung e.V. Verfahren zur Herstellung von Homo- und Copolyestern der Milchsäure
US6656488B2 (en) 2001-04-11 2003-12-02 Ethicon Endo-Surgery, Inc. Bioabsorbable bag containing bioabsorbable materials of different bioabsorption rates for tissue engineering
US6607548B2 (en) * 2001-05-17 2003-08-19 Inion Ltd. Resorbable polymer compositions
US20030069629A1 (en) * 2001-06-01 2003-04-10 Jadhav Balkrishna S. Bioresorbable medical devices
US6599314B2 (en) 2001-06-08 2003-07-29 Cordis Corporation Apparatus and method for stenting a vessel using balloon-actuated stent with interlocking elements
US6645618B2 (en) 2001-06-15 2003-11-11 3M Innovative Properties Company Aliphatic polyester microfibers, microfibrillated articles and use thereof
US6730772B2 (en) 2001-06-22 2004-05-04 Venkatram P. Shastri Degradable polymers from derivatized ring-opened epoxides
KR100448170B1 (ko) 2001-06-23 2004-09-10 주식회사 태평양 폴리에틸렌이민을 친수성 블록으로 갖고 폴리에스테르계고분자를 소수성 블록으로 갖는 양친성 생분해성 블록공중합체 및 이를 이용한 수용액 상에서의 고분자자기조합 회합체
US6585755B2 (en) 2001-06-29 2003-07-01 Advanced Cardiovascular Polymeric stent suitable for imaging by MRI and fluoroscopy
KR100383433B1 (ko) 2001-06-29 2003-05-12 주식회사 씨엠리서치 고강도 뼈 고정용 생분해성 유기 고분자/무기 복합 소재의제조 방법 및 그에 의해 제조된 생분해성 유기고분자/무기 복합 소재
US20030050687A1 (en) 2001-07-03 2003-03-13 Schwade Nathan D. Biocompatible stents and method of deployment
US20060004437A1 (en) 2001-08-29 2006-01-05 Swaminathan Jayaraman Structurally variable stents
US6747121B2 (en) 2001-09-05 2004-06-08 Synthes (Usa) Poly(L-lactide-co-glycolide) copolymers, methods for making and using same, and devices containing same
US20050025808A1 (en) 2001-09-24 2005-02-03 Herrmann Robert A. Medical devices and methods for inhibiting smooth muscle cell proliferation
US20060142765A9 (en) 2001-10-15 2006-06-29 Dixon Robert A Vertebral implant for bone fixation or interbody use
GB0124742D0 (en) 2001-10-16 2001-12-05 Biocomposites Ltd Biodegradable materials
US7572287B2 (en) 2001-10-25 2009-08-11 Boston Scientific Scimed, Inc. Balloon expandable polymer stent with reduced elastic recoil
US20030082148A1 (en) 2001-10-31 2003-05-01 Florian Ludwig Methods and device compositions for the recruitment of cells to blood contacting surfaces in vivo
US7682387B2 (en) 2002-04-24 2010-03-23 Biosensors International Group, Ltd. Drug-delivery endovascular stent and method for treating restenosis
US7595043B2 (en) 2001-12-07 2009-09-29 Cytori Therapeutics, Inc. Method for processing and using adipose-derived stem cells
WO2003051328A1 (en) 2001-12-18 2003-06-26 Novo Nordisk A/S Solid dose micro implant
US8454997B2 (en) 2001-12-18 2013-06-04 Novo Nordisk A/S Solid dose micro implant
EP1458365A1 (en) 2001-12-21 2004-09-22 Celator Technologies Inc. Improved polymer-lipid delivery vehicles
US6866805B2 (en) 2001-12-27 2005-03-15 Advanced Cardiovascular Systems, Inc. Hybrid intravascular stent
CN1246387C (zh) 2001-12-28 2006-03-22 旭电化工业株式会社 聚乳酸型树脂组合物、模塑制品和其制备方法
US20030212449A1 (en) 2001-12-28 2003-11-13 Cox Daniel L. Hybrid stent
US7326245B2 (en) 2002-01-31 2008-02-05 Boston Scientific Scimed, Inc. Medical device for delivering biologically active material
EP1334990A1 (en) 2002-02-06 2003-08-13 Polyganics B.V. DL-Lactide-epsilon-caprolactone copolymers
US6887270B2 (en) 2002-02-08 2005-05-03 Boston Scientific Scimed, Inc. Implantable or insertable medical device resistant to microbial growth and biofilm formation
US20060093771A1 (en) 2002-02-15 2006-05-04 Frantisek Rypacek Polymer coating for medical devices
KR20040097126A (ko) 2002-02-15 2004-11-17 씨브이 쎄러퓨틱스, 인코포레이티드 의료 장치용 중합체 코팅
DE10206924B4 (de) 2002-02-19 2005-12-15 Papierfabrik Schoeller & Hoesch Gmbh & Co. Kg Heisssiegelfähige Filtermaterialien
JP2003253009A (ja) 2002-03-06 2003-09-10 Unitika Ltd ポリ乳酸系成形体およびその製造方法
JP2005529095A (ja) 2002-04-10 2005-09-29 ネモサイエンス、ゲーエムベーハー 毛髪において形状記憶効果を達成する方法
US20050187605A1 (en) 2002-04-11 2005-08-25 Greenhalgh Skott E. Electrospun skin capable of controlling drug release rates and method
US20030195611A1 (en) 2002-04-11 2003-10-16 Greenhalgh Skott E. Covering and method using electrospinning of very small fibers
US20030211135A1 (en) 2002-04-11 2003-11-13 Greenhalgh Skott E. Stent having electrospun covering and method
GB0208418D0 (en) 2002-04-11 2002-05-22 Univ Aston Polymeric fibre
DE10216834A1 (de) 2002-04-16 2003-11-13 Fraunhofer Ges Forschung Verfahren zum Herstellen schmelzestabiler Homo- und Copolyester cyclischer Ester und/oder Diester
DE10217351B3 (de) 2002-04-18 2004-02-12 Mnemoscience Gmbh Interpenetrierende Netzwerke
DE10217350C1 (de) 2002-04-18 2003-12-18 Mnemoscience Gmbh Polyesterurethane
US6890649B2 (en) 2002-04-26 2005-05-10 3M Innovative Properties Company Aliphatic polyester microfibers, microfibrillated articles and use thereof
US6869985B2 (en) 2002-05-10 2005-03-22 Awi Licensing Company Environmentally friendly polylactide-based composite formulations
CN1655738A (zh) 2002-05-20 2005-08-17 奥勃斯医学技术股份有限公司 可植入的药物洗脱医疗装置
US7166133B2 (en) 2002-06-13 2007-01-23 Kensey Nash Corporation Devices and methods for treating defects in the tissue of a living being
US7794743B2 (en) 2002-06-21 2010-09-14 Advanced Cardiovascular Systems, Inc. Polycationic peptide coatings and methods of making the same
US6794484B2 (en) 2002-06-28 2004-09-21 Ethicon, Inc. Crystallizable polylactone copolymers prepared from mono- and di-functional polymerization initiators
US6831149B2 (en) 2002-06-28 2004-12-14 Ethicon, Inc. Polymerization process using mono-and di-functional initiators to prepare fast crystallizing polylactone copolymers
US20040006146A1 (en) 2002-07-06 2004-01-08 Evans Douglas G. Resorbable structure for treating and healing of tissue defects
US7160551B2 (en) 2002-07-09 2007-01-09 The Board Of Trustees Of The University Of Illinois Injectable system for controlled drug delivery
EP1382628A1 (en) 2002-07-16 2004-01-21 Polyganics B.V. Biodegradable phase separated segmented/block co-polyesters
US6916483B2 (en) 2002-07-22 2005-07-12 Biodynamics, Llc Bioabsorbable plugs containing drugs
US7824699B2 (en) 2002-07-22 2010-11-02 Biodynamics Llc Implantable prosthetic devices containing timed release therapeutic agents
US20070100358A2 (en) 2002-08-01 2007-05-03 Texas Scottish Rite Hospital For Children A Biomimetic Synthetic Nerve Implant
WO2004016199A1 (en) 2002-08-15 2004-02-26 Gmp Cardiac Care, Inc. Stent-graft with rails
JP2006500041A (ja) 2002-09-24 2006-01-05 ガムリンク エー／エス 少なくとも２種類の異なる生分解性ポリマーを含有するチューインガム
CA2501059C (en) 2002-09-24 2011-03-01 Gumlink A/S Degradable chewing gum polymer
EP1542739B1 (en) 2002-09-26 2008-12-10 Angiotech International Ag Perivascular wraps
US6770729B2 (en) 2002-09-30 2004-08-03 Medtronic Minimed, Inc. Polymer compositions containing bioactive agents and methods for their use
AU2003300377B2 (en) 2002-10-11 2009-04-02 University Of Connecticut Blends of amorphous and semicrystalline polymers having shape memory properties
US8105652B2 (en) 2002-10-24 2012-01-31 Massachusetts Institute Of Technology Methods of making decomposable thin films of polyelectrolytes and uses thereof
US20040098090A1 (en) 2002-11-14 2004-05-20 Williams Michael S. Polymeric endoprosthesis and method of manufacture
AU2003290698A1 (en) 2002-11-15 2004-06-15 Synecor, Llc Polymeric endoprosthesis and method of manufacture
US7354656B2 (en) 2002-11-26 2008-04-08 Michigan State University, Board Of Trustees Floor covering made from an environmentally friendly polylactide-based composite formulation
EP1578957B1 (en) 2002-12-12 2015-04-15 Warsaw Orthopedic, Inc. Formable and settable polymer bone composite and method of production thereof
US6896697B1 (en) 2002-12-30 2005-05-24 Advanced Cardiovascular Systems, Inc. Intravascular stent
JP2004224990A (ja) 2003-01-27 2004-08-12 Suzuki Motor Corp ポリ乳酸系ポリマー樹脂組成物とその成形品
US7435789B2 (en) 2003-01-31 2008-10-14 Poly-Med, Inc. Crystalline high-compliance glycolide copolymers and applications thereof
JP2006516394A (ja) 2003-02-04 2006-07-06 ガムリンク エー／エス 圧縮チューインガムタブレット
CN1446833A (zh) 2003-02-08 2003-10-08 复旦大学 一种温敏性可降解微凝胶及其制备方法
US20060233887A1 (en) 2003-02-14 2006-10-19 The North West London Hospitals N H S Trust Bioactive material for use in stimulating vascularization
US20040167572A1 (en) 2003-02-20 2004-08-26 Roth Noah M. Coated medical devices
US7918884B2 (en) 2003-02-25 2011-04-05 Cordis Corporation Stent for treatment of bifurcated lesions
US20080051866A1 (en) 2003-02-26 2008-02-28 Chao Chin Chen Drug delivery devices and methods
US20040249442A1 (en) 2003-02-26 2004-12-09 Fleming James A. Locking stent having multiple locking points
US7169118B2 (en) 2003-02-26 2007-01-30 Scimed Life Systems, Inc. Elongate medical device with distal cap
US20060083767A1 (en) 2003-02-27 2006-04-20 Kai Deusch Surgical prosthesis having biodegradable and nonbiodegradable regions
US6932930B2 (en) 2003-03-10 2005-08-23 Synecor, Llc Intraluminal prostheses having polymeric material with selectively modified crystallinity and methods of making same
CA2521623C (en) 2003-04-11 2015-03-17 Etex Corporation Osteoinductive bone material
US7972616B2 (en) 2003-04-17 2011-07-05 Nanosys, Inc. Medical device applications of nanostructured surfaces
CN1320044C (zh) 2003-04-25 2007-06-06 株式会社艾迪科 聚乳酸类树脂组合物、成型品及其制备方法
WO2005018683A2 (en) 2003-05-23 2005-03-03 Angiotech International Ag Anastomotic connector devices
WO2004108180A1 (en) 2003-06-04 2004-12-16 Inion Ltd Biodegradable implant and method for manufacturing one
CA2530032C (en) 2003-06-16 2015-11-24 Loma Linda University Medical Center Deployable multifunctional hemostatic agent
EP1643934A4 (en) 2003-06-16 2008-05-28 Univ Loma Linda Med DEPLOYABLE HEMOSTATIC AGENT
CN100558321C (zh) 2003-06-16 2009-11-11 南洋理工大学 聚合物支架和其制造方法
US6974862B2 (en) 2003-06-20 2005-12-13 Kensey Nash Corporation High density fibrous polymers suitable for implant
US20050118344A1 (en) 2003-12-01 2005-06-02 Pacetti Stephen D. Temperature controlled crimping
AU2003278089A1 (en) 2003-07-03 2005-01-21 Universiteit Twente Biocompatible polymer networks
US20050013812A1 (en) 2003-07-14 2005-01-20 Dow Steven W. Vaccines using pattern recognition receptor-ligand:lipid complexes
DK1498147T3 (da) 2003-07-16 2015-05-26 Eidgenössische Tech Hochschule Zürich Nedbrydelig biokompatibel blokcopolymer
DE10334823A1 (de) 2003-07-30 2005-02-24 Mnemoscience Gmbh Verfahren zur Haarbehandlung mit Formgedächtnispolymeren
DE10334784A1 (de) 2003-07-30 2005-03-03 Mnemoscience Gmbh Kosmetische Zusammensetzung mit Polyol/Polyester Blockpolymeren
US8529625B2 (en) 2003-08-22 2013-09-10 Smith & Nephew, Inc. Tissue repair and replacement
CA2539751C (en) 2003-09-05 2016-04-26 Norian Corporation Bone cement compositions having fiber-reinforcement and/or increased flowability
WO2005039489A2 (en) 2003-09-24 2005-05-06 Polymerix Corporation Compositions and methods for the inhibition of bone growth and resorption
US20060188486A1 (en) 2003-10-14 2006-08-24 Medivas, Llc Wound care polymer compositions and methods for use thereof
US20050202067A1 (en) 2003-10-28 2005-09-15 Gkss Forschungszentrum Matrix structure and hybrid matrix system for inducing a neofacia, their use and method for generating a neofacia
US7264641B2 (en) 2003-11-10 2007-09-04 Cabot Microelectronics Corporation Polishing pad comprising biodegradable polymer
CA2536041A1 (en) 2003-11-10 2005-05-26 Angiotech International Ag Medical implants and fibrosis-inducing agents
EP1682196A2 (en) 2003-11-10 2006-07-26 Angiotech International Ag Medical implants and anti-scarring agents
WO2005051452A2 (en) 2003-11-20 2005-06-09 Angiotech International Ag Polymer compositions and methods for their use
US20050208095A1 (en) 2003-11-20 2005-09-22 Angiotech International Ag Polymer compositions and methods for their use
US8192752B2 (en) 2003-11-21 2012-06-05 Advanced Cardiovascular Systems, Inc. Coatings for implantable devices including biologically erodable polyesters and methods for fabricating the same
US7807722B2 (en) 2003-11-26 2010-10-05 Advanced Cardiovascular Systems, Inc. Biobeneficial coating compositions and methods of making and using thereof
US7481839B2 (en) 2003-12-02 2009-01-27 Kyphon Sarl Bioresorbable interspinous process implant for use with intervertebral disk remediation or replacement implants and procedures
US7723395B2 (en) 2004-04-29 2010-05-25 Kensey Nash Corporation Compressed porous materials suitable for implant
WO2005059003A1 (en) 2003-12-15 2005-06-30 The Children's Hospital Of Philadelphia Novel polyesters
GB0329654D0 (en) 2003-12-23 2004-01-28 Smith & Nephew Tunable segmented polyacetal
AU2005210668A1 (en) 2004-01-30 2005-08-18 Angiotech International Ag Compositions and methods for treating contracture
EP1718147B1 (en) 2004-02-23 2012-03-28 Loma Linda University Medical Center Hemostatic agent for topical and internal use
ATE442822T1 (de) 2004-04-02 2009-10-15 Arterial Remodelling Technolog Stentanordnung auf polymerbasis
US7691381B2 (en) 2004-04-15 2010-04-06 Allergan, Inc. Stabilized biodegradable neurotoxin implants
US8512738B2 (en) 2004-04-30 2013-08-20 Allergan, Inc. Biodegradable intravitreal tyrosine kinase implants
US7820732B2 (en) 2004-04-30 2010-10-26 Advanced Cardiovascular Systems, Inc. Methods for modulating thermal and mechanical properties of coatings on implantable devices
WO2005110437A2 (en) 2004-05-10 2005-11-24 Therics, Inc. Implantable biostructure comprising an osteoconductive member and an osteoinductive material
WO2005114322A2 (en) 2004-05-12 2005-12-01 Massachusetts Institute Of Technology Manufacturing process, such as three-dimensional printing, including solvent vapor filming and the like
US7785615B2 (en) 2004-05-28 2010-08-31 Cordis Corporation Biodegradable medical implant with encapsulated buffering agent
US20060018942A1 (en) 2004-05-28 2006-01-26 Rowe Charles W Polymeric microbeads having characteristics favorable for bone growth, and process including three dimensional printing upon such microbeads
US8012501B2 (en) 2004-06-10 2011-09-06 Synthes Usa, Llc Flexible bone composite
EP1768992A1 (en) 2004-06-24 2007-04-04 Wisconsin Alumni Research Foundation Neoglycorandomization and digitoxin analogs
US8747878B2 (en) 2006-04-28 2014-06-10 Advanced Cardiovascular Systems, Inc. Method of fabricating an implantable medical device by controlling crystalline structure
KR101259770B1 (ko) 2004-07-28 2013-05-03 에디컨인코포레이티드 최소 침습성 의료용 임플란트 및 삽입 장치와 그 사용 방법
KR100895135B1 (ko) 2004-08-13 2009-05-04 마스트 바이오서저리 아게 생분해성 및 난분해성 영역을 갖는 수술용 보철물
AU2005272578A1 (en) 2004-08-13 2006-02-23 Angiotech International Ag Compositions and methods using hyaluronic acid and hyluronidase inhibitors
US20060041102A1 (en) * 2004-08-23 2006-02-23 Advanced Cardiovascular Systems, Inc. Implantable devices comprising biologically absorbable polymers having constant rate of degradation and methods for fabricating the same
US7919112B2 (en) 2004-08-26 2011-04-05 Pathak Holdings, Llc Implantable tissue compositions and method
US7244443B2 (en) 2004-08-31 2007-07-17 Advanced Cardiovascular Systems, Inc. Polymers of fluorinated monomers and hydrophilic monomers
US9011831B2 (en) 2004-09-30 2015-04-21 Advanced Cardiovascular Systems, Inc. Methacrylate copolymers for medical devices
US7166680B2 (en) 2004-10-06 2007-01-23 Advanced Cardiovascular Systems, Inc. Blends of poly(ester amide) polymers
CA2581763A1 (en) 2004-10-13 2006-04-27 Medtronic, Inc. Self-fixating implantable scaffolds for the administration of biological or pharmaceutical substances
US20080095822A1 (en) 2004-11-16 2008-04-24 Universite De Liege Active Substance Delivery System Comprising A Hydrogel Atrix And Microcarriers
US20060115449A1 (en) 2004-11-30 2006-06-01 Advanced Cardiovascular Systems, Inc. Bioabsorbable, biobeneficial, tyrosine-based polymers for use in drug eluting stent coatings
EP1844097A2 (en) 2004-12-10 2007-10-17 University of Connecticut Shape memory polymer orthodontic appliances, and methods of making and using the same
WO2006066572A2 (en) 2004-12-22 2006-06-29 Gumlink A/S Biodegradable chewing gum comprising biodegradable polymer with high glass transition temperature
US7604818B2 (en) 2004-12-22 2009-10-20 Advanced Cardiovascular Systems, Inc. Polymers of fluorinated monomers and hydrocarbon monomers
US8007775B2 (en) 2004-12-30 2011-08-30 Advanced Cardiovascular Systems, Inc. Polymers containing poly(hydroxyalkanoates) and agents for use with medical articles and methods of fabricating the same
US20060198868A1 (en) 2005-01-05 2006-09-07 Dewitt David M Biodegradable coating compositions comprising blends
US20060147491A1 (en) 2005-01-05 2006-07-06 Dewitt David M Biodegradable coating compositions including multiple layers
US7202325B2 (en) 2005-01-14 2007-04-10 Advanced Cardiovascular Systems, Inc. Poly(hydroxyalkanoate-co-ester amides) and agents for use with medical articles
KR100511618B1 (ko) 2005-01-17 2005-08-31 이경범 약물방출 조절형 다층 코팅 스텐트 및 이의 제조방법
US20060240078A1 (en) 2005-03-24 2006-10-26 Clemson University Feed supplement delivery system
US20060224226A1 (en) 2005-03-31 2006-10-05 Bin Huang In-vivo radial orientation of a polymeric implantable medical device
US7842261B2 (en) 2005-04-21 2010-11-30 Purac Biochem Bv Process for preparing resorbable polyesters by bulk polymerization
US8778375B2 (en) 2005-04-29 2014-07-15 Advanced Cardiovascular Systems, Inc. Amorphous poly(D,L-lactide) coating
WO2006135479A2 (en) 2005-05-10 2006-12-21 Angiotech International Ag Anti-scarring agents, therapeutic compositions, and use thereof
US7291166B2 (en) * 2005-05-18 2007-11-06 Advanced Cardiovascular Systems, Inc. Polymeric stent patterns
US20060271170A1 (en) 2005-05-31 2006-11-30 Gale David C Stent with flexible sections in high strain regions
ATE458771T1 (de) 2005-06-03 2010-03-15 Univ Twente Verzweigte polymere, ein makromonomer, verfahren zu deren herstellungen und deren verwendungen
US20060276345A1 (en) 2005-06-07 2006-12-07 Halliburton Energy Servicers, Inc. Methods controlling the degradation rate of hydrolytically degradable materials
US7655584B2 (en) 2005-07-29 2010-02-02 Gore Enterprise Holdings, Inc. Highly porous self-cohered web materials
US7914574B2 (en) 2005-08-02 2011-03-29 Reva Medical, Inc. Axially nested slide and lock expandable device
EP1909774A2 (en) 2005-08-04 2008-04-16 Angiotech International Ag Block copolymer compositions and uses thereof
US7905021B2 (en) 2005-08-10 2011-03-15 Kamran Shirazi International dining kit
US20070034615A1 (en) 2005-08-15 2007-02-15 Klaus Kleine Fabricating medical devices with an ytterbium tungstate laser
US7476245B2 (en) 2005-08-16 2009-01-13 Advanced Cardiovascular Systems, Inc. Polymeric stent patterns
US9248034B2 (en) 2005-08-23 2016-02-02 Advanced Cardiovascular Systems, Inc. Controlled disintegrating implantable medical devices
US20070208134A1 (en) 2005-10-03 2007-09-06 Hunter William L Anti-scarring drug combinations and use thereof
US20070087033A1 (en) 2005-10-14 2007-04-19 Sigg Daniel C Self-fixating scaffolds
CA2626805C (en) 2005-11-15 2016-05-17 Orbusneich Medical, Inc. Progenitor endothelial cell capturing with a drug eluting implantable medical device
DE102005056532A1 (de) 2005-11-28 2007-05-31 Mnemoscience Gmbh Entfernung von tubulären Gewebestützen
DE102005056529A1 (de) 2005-11-28 2007-05-31 Mnemoscience Gmbh Komprimierbare tubuläre Gewebestützen
US9446226B2 (en) 2005-12-07 2016-09-20 Ramot At Tel-Aviv University Ltd. Drug-delivering composite structures
US7849361B2 (en) * 2005-12-22 2010-12-07 Emc Corporation Methods and apparatus for multiple point in time data access
US20070149640A1 (en) 2005-12-28 2007-06-28 Sasa Andjelic Bioabsorbable polymer compositions exhibiting enhanced crystallization and hydrolysis rates
US7902303B2 (en) 2005-12-30 2011-03-08 Industrial Technology Research Institute Aliphatic polyester polymer compositions and preparation method thereof
US20070151961A1 (en) 2006-01-03 2007-07-05 Klaus Kleine Fabrication of an implantable medical device with a modified laser beam
CA2637606C (en) 2006-01-19 2013-03-19 Osteotech, Inc. Porous osteoimplant
EP1976460A4 (en) 2006-01-19 2012-06-20 Warsaw Orthopedic Inc INJECTABLE AND FORMABLE BONE REPLACEMENT MATERIALS
FI20060077L (fi) 2006-01-26 2007-07-27 Seppaelae Jukka Veli Uudet biohajoavat polymeerit
EP2114298B1 (en) 2006-02-08 2022-10-19 Medtronic, Inc. Temporarily stiffened mesh prostheses
US20070224245A1 (en) 2006-02-08 2007-09-27 Northwestern University Poly (diol co-citrate) hydroxyapatite composite for tissue engineering and orthopaedic fixation devices
US8652192B2 (en) 2006-03-31 2014-02-18 St. Jude Medical, Cardiology Division, Inc. Stent and system and method for deploying a stent
US7964210B2 (en) 2006-03-31 2011-06-21 Abbott Cardiovascular Systems Inc. Degradable polymeric implantable medical devices with a continuous phase and discrete phase
US20070231362A1 (en) 2006-04-04 2007-10-04 3M Innovative Properties Company Schistose microfibrillated article for cell growth
US20070238167A1 (en) 2006-04-04 2007-10-11 3M Innovative Properties Company Flat microfibers as matrices for cell growth
EP2007317A2 (en) 2006-04-05 2008-12-31 University Of Nebraska Bioresorbable polymer reconstituted bone and methods of formation thereof
US8350087B2 (en) 2006-04-12 2013-01-08 Agency For Science, Technology And Research Biodegradable thermogelling polymer
US20070254012A1 (en) 2006-04-28 2007-11-01 Ludwig Florian N Controlled degradation and drug release in stents
US7594928B2 (en) 2006-05-17 2009-09-29 Boston Scientific Scimed, Inc. Bioabsorbable stents with reinforced filaments
WO2007140325A2 (en) 2006-05-26 2007-12-06 University Of Nebraska Office Of Technology Development Bioresorbable polymer reconstituted ceramic matrices and methods of formation thereof
US9561351B2 (en) 2006-05-31 2017-02-07 Advanced Cardiovascular Systems, Inc. Drug delivery spiral coil construct
US8486135B2 (en) 2006-06-01 2013-07-16 Abbott Cardiovascular Systems Inc. Implantable medical devices fabricated from branched polymers
EP1864687B1 (en) 2006-06-09 2013-07-31 Eidgenössische Technische Hochschule Zürich Scaffolds for artificial heart valves and vascular structures
EP3009477B1 (en) * 2006-07-20 2024-01-24 Orbusneich Medical Pte. Ltd Bioabsorbable polymeric composition for a medical device
US8460364B2 (en) 2006-07-20 2013-06-11 Orbusneich Medical, Inc. Bioabsorbable polymeric medical device
WO2008011612A2 (en) * 2006-07-20 2008-01-24 Orbusneich Medical, Inc. Bioabsorbable polymeric medical device
EP2073754A4 (en) 2006-10-20 2012-09-26 Orbusneich Medical Inc BIOABSORBABLE POLYMER COMPOSITION AND MEDICAL DEVICE BACKGROUND
US7959942B2 (en) 2006-10-20 2011-06-14 Orbusneich Medical, Inc. Bioabsorbable medical device with coating
US20080177373A1 (en) 2007-01-19 2008-07-24 Elixir Medical Corporation Endoprosthesis structures having supporting features

Also Published As

Publication number Publication date
US20170035946A1 (en) 2017-02-09
CN103122132B (zh) 2016-03-16
US9642947B2 (en) 2017-05-09
WO2008011615A2 (en) 2008-01-24
EP3047860A1 (en) 2016-07-27
US10420863B2 (en) 2019-09-24
US20210308343A1 (en) 2021-10-07
US20150073100A1 (en) 2015-03-12
US20120142869A1 (en) 2012-06-07
US7846361B2 (en) 2010-12-07
US20150073099A1 (en) 2015-03-12
US20080118546A1 (en) 2008-05-22
US7897224B2 (en) 2011-03-01
US9173973B2 (en) 2015-11-03
US8137603B2 (en) 2012-03-20
EP2044140B1 (en) 2017-05-17
US9642945B2 (en) 2017-05-09
US11065369B2 (en) 2021-07-20
US20090281249A1 (en) 2009-11-12
US20230135101A1 (en) 2023-05-04
EP2044140A2 (en) 2009-04-08
US20110130521A1 (en) 2011-06-02
US20180099074A1 (en) 2018-04-12
US9629940B2 (en) 2017-04-25
US9662416B2 (en) 2017-05-30
WO2008011615A3 (en) 2008-07-17
EP3061791A1 (en) 2016-08-31
US8642707B2 (en) 2014-02-04
EP3009477B1 (en) 2024-01-24
US20170035945A1 (en) 2017-02-09
US20200000975A1 (en) 2020-01-02
EP2044140A4 (en) 2014-07-16
US20170189585A1 (en) 2017-07-06
US20200237972A1 (en) 2020-07-30
EP3009477A1 (en) 2016-04-20
HK1222667A1 (zh) 2017-07-07
EP3061791B1 (en) 2019-01-16
US20100003327A1 (en) 2010-01-07

Similar Documents

Publication Publication Date Title
CN103122132B (zh) 用于医疗器械的可生物吸收聚合物组合物
CN101522754B (zh) 用于医疗器械的可生物吸收聚合物组合物
US10392472B2 (en) Biodegradable cross-linked polymer and methods of preparing the same
CN101400385A (zh) 生物可吸收给药装置
PT1042388E (pt) Composições de poli-hidroxialcanoato com velocidades de degradação controladas
AU2014355033A1 (en) Absorbable polymeric blend compositions with precisely controllable absorption rates, processing methods, and dimensionally stable medical devices therefrom
CN102459408A (zh) 生物可吸收的聚合物组合物及医疗器械
CN101400382A (zh) 生产由溶剂浇铸管构成的生物可吸收给药装置的方法
US20200405920A1 (en) Self-expanding stent and manufacturing method therefor
CN101394874A (zh) 生产由溶剂浇铸膜构成的生物可吸收给药装置的方法
Vert Understanding of the Bioresorption of PLA/GA Polymers with Respect

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
TR01 Transfer of patent right

Effective date of registration: 20191101

Address after: Singapore City

Patentee after: Obasnitz medical Sdn Bhd

Address before: Florida, USA

Patentee before: Orbusneich Medical, Inc.

TR01 Transfer of patent right