公开(公告)号：US09226899B2

公开(公告)日：2016-01-05

申请号：US14292734

申请日：2014-05-30

Applicant: AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH

Inventor： Motoichi Kurisawa ,  Shengyong Ng ,  Joo Eun Chung

IPC: A61K9/50 ,  A61K9/16 ,  A61K9/10 ,  A61K31/353 ,  A61K31/7048 ,  A61K31/728 ,  A61K47/48 ,  A61K31/4706 ,  A61K38/48 ,  C07K16/18

CPC classification number: A61K9/1617 ,  A61K9/10 ,  A61K9/1652 ,  A61K31/353 ,  A61K31/4706 ,  A61K31/7048 ,  A61K31/728 ,  A61K38/482 ,  A61K47/61 ,  C07K16/18 ,  A61K2300/00

Abstract: There is presently provided a suspension of immiscible particles in a solution, wherein the particles comprise an agglomeration of a bioactive agent, for example an anti-cancer agent; and a plurality of conjugates of a hyaluronic acid and a flavonoid, for example a catechin-based flavonoid, wherein the particles are on average from about 15 nm to about 300 nm in diameter and wherein the bioactive agent is releasably retained in the particles by the flavonoid. The suspension is useful for delivery of the bioactive agent to cells, including cancer cells. There are also provided a therapeutic formulation comprising the suspension, as well as methods for using the suspension and therapeutic formulation, including for delivery of a bioactive agent to a cell and for treating a disease, including cancer.

Abstract translation: 目前提供了在溶液中的不混溶性颗粒的悬浮液，其中颗粒包括生物活性剂，例如抗癌剂的附聚物; 以及多个透明质酸和类黄酮的缀合物，例如儿茶素类黄酮，其中所述颗粒直径平均为约15nm至约300nm，并且其中所述生物活性剂可释放地保留在颗粒中 类黄酮。 悬浮液可用于将生物活性剂递送至细胞，包括癌细胞。 还提供了包含悬浮液的治疗剂型，以及使用悬浮液和治疗剂型的方法，包括将生物活性剂递送至细胞并用于治疗包括癌症的疾病。

公开(公告)号：US20130338101A1

公开(公告)日：2013-12-19

申请号：US13970432

申请日：2013-08-19

Applicant: Agency for Science, Technology and Research

Inventor： Motoichi Kurisawa ,  Fan Lee ,  Joo Eun Chung ,  Pui Yik Peggy Chan

IPC: A61K31/353 ,  C12P19/26 ,  A61K31/738

CPC classification number: A61K31/353 ,  A61K9/0024 ,  A61K31/015 ,  A61K31/05 ,  A61K31/738 ,  A61K47/61 ,  A61K47/6903 ,  A61L27/54 ,  C08J3/075 ,  C08J2397/00 ,  C12P17/06 ,  C12P19/26

Abstract: There are provided methods for producing a hydrogel that is capable of adhesion of cells and which comprises enzymatically cross-linked conjugates of a hydrogel forming agent and a flavonoid, formed from a reaction using peroxide and peroxidase. Hydrogels produced by such methods and methods of using the hydrogels are also provided.

Abstract translation: 提供了能够产生能够粘附细胞的水凝胶的方法，其包括由使用过氧化物和过氧化物酶的反应形成的水凝胶形成剂和类黄酮的酶交联的缀合物。 还提供了通过使用水凝胶的方法和方法制备的水凝胶。

公开(公告)号：US10716959B2

公开(公告)日：2020-07-21

申请号：US14916559

申请日：2014-09-01

Applicant: AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH

Inventor： Motoichi Kurisawa ,  Ki Hyun Bae

IPC: A61K47/48 ,  A61K9/06 ,  A61K8/73 ,  A61K8/49 ,  A61K9/00 ,  A61K31/353 ,  A61K8/04 ,  A61Q19/00 ,  C07D311/32 ,  A61K8/81 ,  A61K47/61 ,  A61K47/36 ,  A61K47/32

Abstract: There is provided polymer-flavonoid conjugates. Flavonoid-grafted and flavonoid-terminated polymer conjugates are disclosed according to the invention. The linkage of flavonoids to the polymers has been achieved via thiol linkages. The inventive processes allow for making of the conjugates in high yield avoiding complex purification steps. The conjugates can be easily autoxidized to hydrogels with uses in many biomedical applications where a higher stability of the flavonoid is necessary. The hydrogels can be potentially used as viscosupplement, anti-adhesion film or dermal filler.

公开(公告)号：US10406175B2

公开(公告)日：2019-09-10

申请号：US15308725

申请日：2015-05-15

Applicant: Agency for Science, Technology and Research

Inventor： Motoichi Kurisawa ,  Fan Lee

IPC: A61K47/48 ,  A61K31/353 ,  A61K31/728 ,  C08B37/00 ,  C08L5/08 ,  C08B37/08 ,  A61K9/00 ,  A61K47/61

Abstract: There is provided a polymer-flavonoid conjugate, or a pharmaceutically acceptable salt thereof, uses thereof, and methods of making thereof. The disclosed polymer-flavonoid conjugates may be useful in the therapeutic and/or prophylactic treatment of a joint condition in a subject.

公开(公告)号：US20190262271A1

公开(公告)日：2019-08-29

申请号：US16343434

申请日：2017-12-29

Applicant: AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH

Inventor： Motoichi Kurisawa ,  Ki Hyun Bae ,  Susi Tan

IPC: A61K9/50 ,  A61K9/51 ,  A61P35/00 ,  A61K33/243 ,  A61K31/282

Abstract: There is provided a nanocomplex having a core-shell structure. The shell of the nanocomplex comprises a functionalized hyaluronic acid while the core of the nanocomplex comprises a flavonoid encapsulating a metal-containing compound. Preferably, the flavonoid is epigallocatechin gallate (EGCG) and the hyaluronic acid is thiol-functionalized and subsequently conjugated to the flavonoid. There is also provided a method of forming the nanocomplex, a pharmaceutical composition comprising the nanocomplex, medical uses of the nanocomplex and a method of treating a patient, preferably with cancer using the nanocomplex.

公开(公告)号：US20170258757A1

公开(公告)日：2017-09-14

申请号：US15598407

申请日：2017-05-18

Applicant: Agency for Science, Technology and Research

Inventor： Motoichi Kurisawa ,  Kun Liang ,  Susi Tan ,  Joo Eun Chung ,  Jackie Y. Ying

IPC: A61K31/282 ,  A61K9/107 ,  A61K31/353 ,  A61K31/704 ,  A61K31/7088 ,  A61K45/06 ,  A61K9/00 ,  A61K31/337

CPC classification number: A61K31/282 ,  A61K9/0019 ,  A61K9/1075 ,  A61K31/337 ,  A61K31/353 ,  A61K31/704 ,  A61K31/7088 ,  A61K45/06 ,  A61K47/60 ,  A61K2300/00

Abstract: There is provided a conjugate of a delivery agent containing a chemical moiety and at least one flavonoid. The flavonoid exists in a monomeric form or dimeric form before conjugation and remains in the monomeric form or dimeric form after conjugation. Preferably, the conjugate comprises two flavonoids. The delivery agent is conjugated at the C6 and/or the C8 position of the A ring of the flavonoid. An anti-cancer agent delivery vehicle comprising an anti-cancer agent and the conjugate is also provided.

公开(公告)号：US09439886B2

公开(公告)日：2016-09-13

申请号：US14697565

申请日：2015-04-27

Applicant: Agency for Science, Technology and Research

Inventor： Motoichi Kurisawa ,  Fan Lee ,  Joo Eun Chung ,  Pui Yik Peggy Chan

IPC: A61F2/02 ,  A61K31/353 ,  A61K31/015 ,  A61K31/05 ,  C12P17/06 ,  A61K9/00 ,  A61L27/54 ,  A61K47/48 ,  C08J3/075 ,  A61K31/738 ,  C12P19/26

CPC classification number: A61K31/353 ,  A61K9/0024 ,  A61K31/015 ,  A61K31/05 ,  A61K31/738 ,  A61K47/61 ,  A61K47/6903 ,  A61L27/54 ,  C08J3/075 ,  C08J2397/00 ,  C12P17/06 ,  C12P19/26

Abstract: There is provided methods for producing a hydrogel comprising conjugates of a hydrogel forming agent and a flavonoid including a method for producing a hydrogel that is capable of adhesion of cells and which comprises enzymatically cross-linked conjugates of a hydrogel forming agent and a flavonoid. There is also provided a method for producing a hydrogel comprising conjugates of a hydrogel forming agent and a flavonoid without the addition of an exogenous peroxide or peroxidase or without the addition of an exogenous peroxide. Hydrogels produced by such methods and methods of using the hydrogels are also described herein.

Abstract translation: 提供了包含水凝胶形成剂和类黄酮的缀合物的水凝胶的方法，包括能够粘附细胞的水凝胶的制造方法，其包含水凝胶形成剂和类黄酮的酶交联的缀合物。 还提供了一种制备水凝胶的方法，其包括水凝胶形成剂和类黄酮的缀合物，而不加入外源性过氧化物酶或过氧化物酶或不加入外源过氧化物。 本文还描述了通过这些使用水凝胶的方法和方法生产的水凝胶。

公开(公告)号：US10993917B2

公开(公告)日：2021-05-04

申请号：US16343434

申请日：2017-12-29

Applicant: AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH

Inventor： Motoichi Kurisawa ,  Ki Hyun Bae ,  Susi Tan

IPC: A61K9/50 ,  A61P35/00 ,  A61K47/61 ,  A61K33/243 ,  A61K9/51 ,  A61K31/282 ,  A61K31/41 ,  A61K31/555 ,  A61K47/69 ,  A61K31/665

Abstract: There is provided a nanocomplex having a core-shell structure. The shell of the nanocomplex comprises a functionalized hyaluronic acid while the core of the nanocomplex comprises a flavonoid encapsulating a metal-containing compound. Preferably, the flavonoid is epigallocatechin gallate (EGCG) and the hyaluronic acid is thiol-functionalized and subsequently conjugated to the flavonoid. There is also provided a method of forming the nanocomplex, a pharmaceutical composition comprising the nanocomplex, medical uses of the nanocomplex and a method of treating a patient, preferably with cancer using the nanocomplex.

公开(公告)号：US10052389B2

公开(公告)日：2018-08-21

申请号：US14767784

申请日：2014-02-13

Applicant: Agency for Science, Technology and Research

Inventor： Motoichi Kurisawa ,  Ki Hyun Bae ,  Fan Lee

IPC: A61K47/61 ,  A61K47/69 ,  A61K47/48 ,  A61L27/20 ,  A61L27/22 ,  A61L27/48 ,  A61L27/52 ,  A61L27/54 ,  A61L31/04 ,  A61L31/12 ,  A61L31/14 ,  A61L31/16 ,  A61L15/44 ,  A61L15/60 ,  A61K9/00 ,  A61K47/10 ,  A61K47/36 ,  A61K38/21 ,  A61K38/28 ,  A61K38/38 ,  C08B37/02 ,  C08L5/02 ,  A61K47/60

CPC classification number: A61K47/61 ,  A61K9/0019 ,  A61K9/0024 ,  A61K38/21 ,  A61K38/212 ,  A61K38/28 ,  A61K38/385 ,  A61K47/10 ,  A61K47/36 ,  A61K47/60 ,  A61K47/6903 ,  A61L15/44 ,  A61L15/60 ,  A61L27/20 ,  A61L27/22 ,  A61L27/48 ,  A61L27/52 ,  A61L27/54 ,  A61L31/042 ,  A61L31/043 ,  A61L31/129 ,  A61L31/145 ,  A61L31/16 ,  A61L2300/622 ,  A61L2400/06 ,  C08B37/0021 ,  C08L5/02 ,  C08L89/00 ,  C08L5/00 ,  C08L71/02

Abstract: The present disclosure relates to a polymeric system for release of an active agent, comprising a first polymeric phase containing the active agent, the first polymeric phase forming discrete regions of a set size range and being dispersed within a second polymeric phase comprising a cross-linked polymer-phenol conjugate for release of the active agent therein. The present disclosure further provides an injectable hydrogel comprising the disclosed polymeric system, a carrier for delivering a biologically active substance or a drug comprising the injectable hydrogel, and a method for producing the disclosed polymeric system.

公开(公告)号：US20150374838A1

公开(公告)日：2015-12-31

申请号：US14767784

申请日：2014-02-13

Applicant: AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH

Inventor： Motoichi Kurisawa ,  Ki Hyun Bae ,  Fan Lee

IPC: A61K47/48 ,  A61K38/21 ,  A61K9/00 ,  A61K38/38 ,  A61K38/28

CPC classification number: A61K47/61 ,  A61K9/0019 ,  A61K9/0024 ,  A61K38/21 ,  A61K38/212 ,  A61K38/28 ,  A61K38/385 ,  A61K47/10 ,  A61K47/36 ,  A61K47/60 ,  A61K47/6903 ,  A61L15/44 ,  A61L15/60 ,  A61L27/20 ,  A61L27/22 ,  A61L27/48 ,  A61L27/52 ,  A61L27/54 ,  A61L31/042 ,  A61L31/043 ,  A61L31/129 ,  A61L31/145 ,  A61L31/16 ,  A61L2300/622 ,  A61L2400/06 ,  C08B37/0021 ,  C08L5/02 ,  C08L89/00 ,  C08L5/00 ,  C08L71/02

Abstract: The present disclosure relates to a polymeric system for release of an active agent, comprising a first polymeric phase containing the active agent, the first polymeric phase forming discrete regions of a set size range and being dispersed within a second polymeric phase comprising a cross-linked polymer-phenol conjugate for release of the active agent therein. The present disclosure further provides an injectable hydrogel comprising the disclosed polymeric system, a carrier for delivering a biologically active substance or a drug comprising the injectable hydrogel, and a method for producing the disclosed polymeric system.

Abstract translation: 本公开涉及一种用于释放活性剂的聚合物体系，其包含含有活性剂的第一聚合物相，所述第一聚合物相形成一定大小范围的离散区域并分散在包含交联的第二聚合物相 聚合物 - 苯酚共轭物用于其中活性剂的释放。 本公开进一步提供了包含所公开的聚合物体系的可注射水凝胶，用于递送生物活性物质的载体或包含可注射水凝胶的药物，以及用于制备所公开的聚合物体系的方法。