公开(公告)号：WO2014022501A3

公开(公告)日：2014-03-27

申请号：PCT/US2013052911

申请日：2013-07-31

Applicant: UNIV AKRON ,  WEISS ROBERT A ,  BECKER MATTHEW

Inventor： WEISS ROBERT A ,  BECKER MATTHEW

IPC: A61K47/34

CPC classification number: C08L71/00 ,  A61K9/06 ,  A61K47/34 ,  C08G65/325 ,  C08G65/33389 ,  C08L71/02 ,  C08L89/00 ,  C08L2205/02

Abstract: The present invention is directed to a covalently crosslinked hydrogel comprising the strain-promoted reaction product of an 8-member cycloalkyne functionalized polyalkylene glycol and a multi-arm glycerol exytholate triazide and methods for making them. Because the precursor materials can be manipulated without causing crosslinking, provided the strain threshold is not reached, these hydrogels permit mechanical control over when (and where) cross linking occurs and are easier to use than prior strain-activated or temperature-activated systems. These novel hydrogels do not require a catalyst to cross link, thus avoiding the biocompatibility problems common to many catalysts. Nor is the crosslinking process affected by the presence of catalysts or other substances, which have interfered with crosslinking in known strain induced hydrogels. Because of their crosslinking reaction kinetics, these novel hydrogels can encapsulate and transport highly sensitive cells and other biological additives and have no known toxic byproducts.

Abstract translation: 本发明涉及一种共价交联的水凝胶，其包含8-元环炔官能化聚亚烷基二醇的应变促进反应产物和多臂甘油异戊酸酯三叠氮化物及其制备方法。 因为前体材料可以在不引起交联的情况下被操纵，只要未达到应变阈值，这些水凝胶允许机械控制何时发生交联（并且在何处发生），并且比以前的应变活化或温度激活的系统更容易使用。 这些新颖的水凝胶不需要催化剂交联，从而避免许多催化剂常见的生物相容性问题。 交联过程也不受催化剂或其他物质的存在的影响，这些物质干扰已知应变诱导的水凝胶中的交联。 由于它们的交联反应动力学，这些新颖的水凝胶可以包封和输送高敏感性细胞和其他生物添加剂，并且没有已知的有毒副产物。

公开(公告)号：EP3063205A4

公开(公告)日：2017-07-19

申请号：EP14857175

申请日：2014-10-29

Applicant: UNIV AKRON

Inventor： BECKER MATTHEW ,  RENEKER DARRELL ,  GAO YAOHUA

IPC: C08G71/00 ,  A61F2/02 ,  A61F2/06 ,  A61F2/07 ,  A61F2/82 ,  A61L27/18 ,  A61L27/50 ,  A61L27/58 ,  C08G69/10 ,  C08G69/44 ,  C08G71/02 ,  C08L77/12 ,  C09D175/02 ,  D01D5/00 ,  D01F6/68 ,  D01F6/84

CPC classification number: A61L27/18 ,  A61F2/06 ,  A61F2/07 ,  A61F2/82 ,  A61F2210/0004 ,  A61F2230/0069 ,  A61F2240/001 ,  A61L27/507 ,  A61L27/58 ,  A61L2400/12 ,  C08G69/10 ,  C08G69/44 ,  C08G71/00 ,  C08G71/02 ,  C08G2230/00 ,  C09D175/02 ,  D01D5/003 ,  D01F6/68 ,  D01F6/84 ,  C08L77/12

Abstract: Embodiments relate to amino acid-based poly(ester urea)s with amino acid residues selected L-leucine, L-isoleucine, L-valine or combinations thereof. The amino acid-based poly(ester urea)S may optionally include a second amino acid residue selected from proteinogenic amino acids and non-proteinogenic amino acids. The amino acid-based poly(ester urea)s are particular useful for the preparation of vascular grafts. Due to the biocompatibility of the amino acid-based poly(ester urea)s, vascular grafts prepared from amino acid-based poly(ester urea)s with small internal diameters (i.e. less than 5 mm) may be prepared and inserted into a patient or animal, and provide a substantial decrease in the risk of failure compared to conventional polymers used in vascular grafts.

Abstract translation: 实施方案涉及氨基酸残基选自L-亮氨酸，L-异亮氨酸，L-缬氨酸或其组合的基于氨基酸的聚（酯脲）。 基于氨基酸的聚（酯脲）S可以任选地包含选自蛋白质原氨基酸和非蛋白原氨基酸的第二氨基酸残基。 基于氨基酸的聚（酯脲）对于制备血管移植物特别有用。 由于基于氨基酸的聚（酯脲）的生物相容性，可制备由具有小内径（即小于5mm）的基于氨基酸的聚（酯脲）制备的血管移植物并将其插入患者体内 或动物，并且与用于血管移植物的常规聚合物相比，显着降低失败风险。

公开(公告)号：EP3052471A4

公开(公告)日：2017-06-14

申请号：EP14848810

申请日：2014-09-30

Applicant: UNIV AKRON

Inventor： BECKER MATTHEW ,  LIN FEI

IPC: C07C229/00 ,  A61L27/00 ,  A61L31/00 ,  C07C225/16 ,  C07C227/18 ,  C07C229/34 ,  C07C247/04 ,  C07C275/16 ,  C08G63/91 ,  C08G71/02 ,  C08G75/02 ,  C08G77/04 ,  C09D175/02

CPC classification number: C08G71/02 ,  C07C227/18 ,  C07C229/34 ,  C07C247/04 ,  C07C275/16 ,  C08G2230/00 ,  C09D175/02

Abstract: Amino acid-based poly(ester urea)s (PEU) are emerging as a class of polymers that have shown promise in regenerative medicine applications. Embodiments of the invention relate to the synthesis of PEUs carrying pendent “clickable” groups on modified tyrosine amino acids. The pendent species include alkyne, azide, alkene, tyrosine-phenol, and ketone groups. PEUs with Mw exceeding 100k Da were obtained via interfacial polycondensation methods and the concentration of pendent groups was varied by copolymerization. The incorporation of derivatizable functionalities is demonstrated using 1H NMR and UV-Vis spectroscopy methods. Electrospinning was used to fabricate PEU nanofibers with a diameters ranging from 350 nm to 500 nm. The nanofiber matricies possess mechanical strengths suitable for tissue engineering (Young's modulus: 300±45 MPa; tensile stress: 8.5±1.2 MPa). A series of bioactive peptides and fluorescent molecules were conjugated to the surface of the nanofibers following electrospinning using bio-orthogonal reactions in aqueous media.

Abstract translation: 基于氨基酸的聚（酯脲）（PEU）正在成为一类在再生医学应用中显示出前景的聚合物。 本发明的实施方案涉及在修饰的酪氨酸氨基酸上携带悬挂的“可点击”基团的PEU的合成。 悬挂物种包括炔烃，叠氮化物，烯烃，酪氨酸 - 苯酚和酮基团。 通过界面缩聚法获得Mw超过100kDa的PEU，并且通过共聚改变侧基的浓度。 使用1 H NMR和UV-Vis光谱学方法证实了可衍生官能团的结合。 静电纺丝被用于制造直径范围从350nm到500nm的PEU纳米纤维。 纳米纤维材料具有适合于组织工程学的机械强度（杨氏模量：300±45MPa;拉伸应力：8.5±1.2MPa）。 在含水介质中使用生物正交反应进行电纺丝后，将一系列生物活性肽和荧光分子缀合至纳米纤维的表面。

公开(公告)号：EP3166553A4

公开(公告)日：2018-02-14

申请号：EP15818436

申请日：2015-07-13

Applicant: UNIV AKRON

Inventor： BECKER MATTHEW ,  TANG WEN

IPC: A61F13/00 ,  A61K38/00 ,  A61K38/18

CPC classification number: A61K47/10 ,  C07K7/08 ,  C07K14/51

Abstract: In various aspects, embodiments of the present invention are directed to a series of multivalent dendrons containing a bioactive peptide domain and surface-binding catechol domains. In some embodiments, these multivalent dendrons were obtained through solid phase synthesis and have a strong binding affinity to metal oxide surfaces such as, TiO2, ZrO2, CeO2, and Fe3O4, SiO2, as well as other inorganic surfaces such as hydroxyapatite, silver, fluorapatite, calcium carbonate and gold. These catechol-bearing dendrons provide a fast and efficient method to functionalize a wide range of inorganic materials with bioactive peptides and have the potential to be used in coating orthopaedic implants and fixation devices.

公开(公告)号：EP2714721A4

公开(公告)日：2014-11-19

申请号：EP12793034

申请日：2012-05-25

Applicant: UNIV AKRON

Inventor： BECKER MATTHEW ,  GRAHAM MATTHEW ,  HARRIS FRANK ,  LIN FEI

IPC: C07K14/00 ,  C08F222/38

CPC classification number: C07K7/06 ,  C07K7/08

公开(公告)号：EP3140340A4

公开(公告)日：2018-04-11

申请号：EP15788781

申请日：2015-05-07

Applicant: UNIV AKRON

Inventor： BECKER MATTHEW ,  LI SHAN

IPC: C08G71/02

CPC classification number: C08G71/02 ,  A61L27/18 ,  A61L27/56

Abstract: In one or more embodiments, the present invention provides iodine-functionalized phenylalanine-based poly(ester urea)s (PEUs) (and related methods for their synthesis and use) that are metal free, degradable, radiopaque and suitable for use in surgical implants and other medical devices used within a patient. In one or more embodiment of the present invention 4-Iodo-L-phenylalanine and L-phenylalanine are separately reacted with 1,6-hexanediol to produce two monomers, bis-4-I-L-phenylalanine-1,6-hexanediol-diester (1-IPHE-6 monomer) and bis-L-phenylalanine-1,6-hexanediol-diester (1-PHE-6 monomer). It has been found that by varying the feed ratio of the 1-IPHE-6 and 1-PHE-6 monomers, the copolymer composition may be modulated to predictably create phenylalanine-based PEUs having a wide variation in thermal, mechanical and radiopacity properties. As most medical device procedures require placement verification via fluoroscopic imaging, materials that possess inherent X-ray contrast are valuable for a number of applications.

公开(公告)号：WO2016081587A9

公开(公告)日：2017-07-27

申请号：PCT/US2015061314

申请日：2015-11-18

Applicant: BECKER MATTHEW ,  DEAN HOWARD ,  LUO YUANYUAN ,  UNIV AKRON ,  THE OHIO STATE UNIV

Inventor： BECKER MATTHEW ,  DEAN HOWARD ,  LUO YUANYUAN

IPC: C08G63/52 ,  A61L27/18 ,  B29C67/00 ,  C08G63/78 ,  C08G63/90

CPC classification number: C08G63/78 ,  A61L27/18 ,  A61L27/56 ,  B33Y70/00 ,  C08G63/52 ,  C08G63/90 ,  C08L67/06

Abstract: The present invention provides a low molecular mass PPF polymer (and related methods) that is suitable for 3D printing and other polymer device fabrication modalities and can be made inexpensively in commercially reasonable quantities. These novel low molecular mass PPF polymers have a low molecular mass distribution (Đm) and a wide variety of potential uses, particularly as a component in resins for 3D printing of medical devices. The ability to produce low Đm PPF creates a new opportunity for reliable GMP production of PPF. It provides low cost synthesis and scalability of synthesis, blending of well-defined mass and viscosity PPF, and reduced reliance on solvents or heat to (a) achieve mixing of 3D printable resins or (b) and flowability during 3D printing. These PPF polymers are non-toxic, degradable, and resorbable and can be used in tissue scaffolds and medical devices that are implanted within a living organism.

Abstract translation: 本发明提供了适用于3D印刷和其他聚合物器件制造模式的低分子量PPF聚合物（和相关方法），并且可以以商业合理的数量廉价制造。 这些新型低分子量PPF聚合物具有低分子量分布（Đm）和广泛的潜在用途，特别是作为医疗器械3D打印树脂的组分。 生产低ðmPPF的能力为PPF的可靠GMP生产创造了新机会。 它提供低成本的合成和合成的可缩放性，混合良好定义的质量和粘度PPF，以及减少对溶剂或热量的依赖，以（a）实现3D可印刷树脂的混合或（b）和3D打印期间的流动性。 这些PPF聚合物无毒，可降解和可再吸收，可用于组织支架和植入生物体内的医疗器械。

公开(公告)号：WO2014210132A3

公开(公告)日：2015-03-19

申请号：PCT/US2014044060

申请日：2014-06-25

Applicant: BECKER MATTHEW ,  TANG WEN ,  UNIV AKRON

Inventor： BECKER MATTHEW ,  TANG WEN

IPC: A61K38/00 ,  A61F13/00 ,  A61K31/74 ,  A61K38/18

CPC classification number: A61K47/62 ,  A61K47/557 ,  A61K47/60

Abstract: The present invention is generally directed a series of novel multivalent, HA-binding peptide bioconjugates with variable dendron valency and tether length, which afford the ability to precisely tune the desired binding behavior, as well as related methods and uses. Certain of these novel multivalent, HA-binding peptide bioconjugates have been found to have a 300-fold increase in binding affinity compared to HA-binding peptide sequences reported previously.

Abstract translation: 本发明通常涉及一系列具有可变枝状突变体和连接臂长度的新颖多价HA结合肽生物缀合物，其提供精确调节所需结合行为的能力以及相关方法和用途。 已经发现，与先前报道的HA结合肽序列相比，这些新型多价HA结合肽生物缀合物中的某些具有结合亲和力增加300倍。

公开(公告)号：EP3171880A4

公开(公告)日：2017-12-13

申请号：EP15824638

申请日：2015-07-21

Applicant: UNIV AKRON

Inventor： BECKER MATTHEW ,  ZHOU JINJUN ,  DEFANTE ADRIAN ,  DHINOJWALA ALI

IPC: A61K31/765 ,  A61K8/02 ,  A61K8/84 ,  A61K8/85 ,  A61K9/00 ,  A61K47/34 ,  A61L26/00 ,  A61Q1/02 ,  A61Q19/00 ,  C08G71/02 ,  C09J175/02

CPC classification number: C08G71/02 ,  A61K8/0204 ,  A61K8/84 ,  A61K8/85 ,  A61K9/0014 ,  A61K47/34 ,  A61K2800/10 ,  A61L26/0019 ,  A61Q1/025 ,  A61Q19/00 ,  C09J175/02

Abstract: The present invention is directed to a novel group of amino acid-based poly(ester urea)s (PEUs) for use in biodegradable adhesive and related methods for their making and use. These novel amino acid-based PEUs have a wide variation in mechanical properties and degradation behavior that can be tuned by varying the amino acids and polyols used to form the polyester monomers that form the PEUs. Importantly, these novel PEUs have been shown to be non-toxic in vitro and in vivo and may be suitable to a wide variety of biomedical and other uses. In some embodiments, the adhesive properties of these degradable amino acid-based poly(ester urea) adhesives has been further improved by the incorporation of controlled amounts of catechol functional groups into the side chains of the PEU via post-polymerization functionalization chemistry.

公开(公告)号：EP2879716A4

公开(公告)日：2016-03-02

申请号：EP13825218

申请日：2013-07-31

Applicant: UNIV AKRON

Inventor： WEISS ROBERT A ,  BECKER MATTHEW

IPC: A61K47/34 ,  A61K9/06 ,  C08G65/325 ,  C08G65/333 ,  C08L71/00 ,  C08L71/02 ,  C08L89/00

CPC classification number: C08L71/00 ,  A61K9/06 ,  A61K47/34 ,  C08G65/325 ,  C08G65/33389 ,  C08L71/02 ,  C08L89/00 ,  C08L2205/02

Abstract: The present invention is directed to a covalently crosslinked hydrogel comprising the strain-promoted reaction product of an 8-member cycloalkyne functionalized polyalkylene glycol and a multi-arm glycerol exytholate triazide and methods for making them. Because the precursor materials can be manipulated without causing crosslinking, provided the strain threshold is not reached, these hydrogels permit mechanical control over when (and where) cross linking occurs and are easier to use than prior strain-activated or temperature-activated systems. These novel hydrogels do not require a catalyst to cross link, thus avoiding the biocompatibility problems common to many catalysts. Nor is the crosslinking process affected by the presence of catalysts or other substances, which have interfered with crosslinking in known strain induced hydrogels. Because of their crosslinking reaction kinetics, these novel hydrogels can encapsulate and transport highly sensitive cells and other biological additives and have no known toxic byproducts.