ECSP11011240A - Conjugados de insulina cristalina - Google Patents

Conjugados de insulina cristalina

Info

Publication number
ECSP11011240A
ECSP11011240A EC2011011240A ECSP11011240A ECSP11011240A EC SP11011240 A ECSP11011240 A EC SP11011240A EC 2011011240 A EC2011011240 A EC 2011011240A EC SP11011240 A ECSP11011240 A EC SP11011240A EC SP11011240 A ECSP11011240 A EC SP11011240A
Authority
EC
Ecuador
Prior art keywords
insulin
crystalline
formulations
conjugates
protamine
Prior art date
Application number
EC2011011240A
Other languages
English (en)
Inventor
Tod C Zion
Thomas M Lancaster
Original Assignee
Smartcells 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 Smartcells Inc filed Critical Smartcells Inc
Publication of ECSP11011240A publication Critical patent/ECSP11011240A/es

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/61—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/575—Hormones
    • C07K14/62—Insulins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/28—Insulins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
    • A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/12—Antidiuretics, e.g. drugs for diabetes insipidus
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K17/00—Carrier-bound or immobilised peptides; Preparation thereof
    • C07K17/02—Peptides being immobilised on, or in, an organic carrier
    • C07K17/10—Peptides being immobilised on, or in, an organic carrier the carrier being a carbohydrate

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Diabetes (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Organic Chemistry (AREA)
  • Endocrinology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Zoology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Hematology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Obesity (AREA)
  • Emergency Medicine (AREA)
  • Toxicology (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

En un aspecto, la divulgación proporciona métodos para controlar los perfiles farmacocinéticos (PK) y/o farmacodinámicos (PD) de insulina de una forma que es sensible a las concentraciones sistémicas de un sacárido tal como la glucosa. Como se discute en los Ejemplos, se descubrió que cuando la insulina fuera conjugada con ligandos sacáridos de alta afinidad, pudo hacerse para exhibir perfiles PK/PD que respondieran a cambios de concentración sacárida aún en ausencia de una molécula multivalente y exógena fijadora de sacáridos tal como Con A. Este hallazgo fue inesperado y proporciona una oportunidad sin precedentes para generar sistemas simples de insulina sensibles a sacáridos libres de lectina.Las formulaciones de liberación sostenida de insulinas convencionales comúnmente se utilizan para retardar la liberación de insulina en circulación sistémica. Por ejemplo, las formulaciones PZI (insulina de protamina de zinc) pueden utilizarse para este propósito. Cuando se formulan insulinas convencionales con protamina y zinc, generalmente se producen formulaciones de liberación sostenida cristalinas. Por el contrario, cuando se formulan los conjugados de insulina descritos en la presente con protamina y zinc utilizando métodos similares, se producen formulaciones amorfas, y se requiere mucha más protamina y zinc para proporcionar liberación sostenida que la requerida para insulinas convencionales, ej. RHI (insulina humana recombinante). Sorprendentemente se ha descubierto que ciertos conjugados de insulina descritos en la presente pueden cristalizarse. Los conjugados de insulina son difíciles de cristalizar utilizando condiciones estándares de cristalización de insulina, más probablemente debido a sus estructuras estéricamente voluminosas que contienen sacáridos. Como se describió en la presente, los conjugados de insulina cristalina de la presente divulgación pueden entonces formularse para proporcionar formulaciones de liberación sostenida cristalinas. La presente divulgación proporciona conjugados de insulina cristalina y formulaciones de los mismos. También se proporcionan métodos para fabricar y utilizar conjugados de insulina cristalina. Las formulaciones cristalinas de los conjugados de insulina pueden ser ventajosas para mejorar reproducibilidad de lote en lote, aumentando estabilidad de la formulación, y disminuyendo la aglomeración de partículas durante largos periodos de almacenamiento.
EC2011011240A 2009-01-28 2011-07-28 Conjugados de insulina cristalina ECSP11011240A (es)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US14787809P 2009-01-28 2009-01-28
US15964309P 2009-03-12 2009-03-12
US16210709P 2009-03-20 2009-03-20
US16308409P 2009-03-25 2009-03-25
US21989709P 2009-06-24 2009-06-24
US22357209P 2009-07-07 2009-07-07
US25285709P 2009-10-19 2009-10-19

Publications (1)

Publication Number Publication Date
ECSP11011240A true ECSP11011240A (es) 2011-11-30

Family

ID=42395986

Family Applications (1)

Application Number Title Priority Date Filing Date
EC2011011240A ECSP11011240A (es) 2009-01-28 2011-07-28 Conjugados de insulina cristalina

Country Status (24)

Country Link
US (5) US9050370B2 (es)
EP (1) EP2391218B1 (es)
JP (3) JP5508438B2 (es)
KR (2) KR101635689B1 (es)
CN (2) CN105753965A (es)
AU (2) AU2015202871B2 (es)
BR (1) BRPI1007457A2 (es)
CA (2) CA2932926C (es)
CO (1) CO6400173A2 (es)
CR (1) CR20110408A (es)
DO (1) DOP2011000244A (es)
EA (1) EA027757B1 (es)
EC (1) ECSP11011240A (es)
ES (1) ES2791683T3 (es)
GT (1) GT201100208A (es)
IL (1) IL214099A0 (es)
MA (1) MA33064B1 (es)
MX (1) MX2011007929A (es)
NI (1) NI201100150A (es)
NZ (1) NZ594248A (es)
PE (1) PE20120583A1 (es)
SG (3) SG173112A1 (es)
TN (1) TN2011000354A1 (es)
WO (1) WO2010088294A1 (es)

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010088268A1 (en) 2009-01-28 2010-08-05 Smartcells, Inc. Exogenously triggered controlled release materials and uses thereof
WO2010088286A1 (en) 2009-01-28 2010-08-05 Smartcells, Inc. Synthetic conjugates and uses thereof
BRPI1007457A2 (pt) 2009-01-28 2015-08-25 Smartcells Inc Conjungado, formulação de liberação prolongada, e, sistema de distribuição de bomba.
US9095623B2 (en) 2009-03-20 2015-08-04 Smartcells, Inc. Terminally-functionalized conjugates and uses thereof
US8623345B2 (en) 2009-03-20 2014-01-07 Smartcells Terminally-functionalized conjugates and uses thereof
AU2011282977A1 (en) * 2010-07-28 2013-02-21 Smartcells, Inc. Drug-ligand conjugates, synthesis thereof, and intermediates thereto
EP2598522A4 (en) 2010-07-28 2014-11-12 Smartcells Inc RECOMBINANT LKTINE, BINDING POINT MODIFIED LECTIN AND APPLICATIONS THEREOF
JP2013535467A (ja) 2010-07-28 2013-09-12 スマートセルズ・インコーポレイテツド 組換えにより発現されたインスリンポリペプチドおよびその使用
AU2011282983A1 (en) * 2010-07-28 2013-02-21 Smartcells, Inc. Drug-ligand conjugates, synthesis thereof, and intermediates thereto
WO2012050822A1 (en) * 2010-10-14 2012-04-19 Smartcells, Inc. Uses of macrophage mannose receptor to screen compounds and uses of these compounds
AR087433A1 (es) * 2011-08-08 2014-03-26 Merck Sharp & Dohme Analogos de insulina n-glicosilados
TWI439288B (zh) * 2012-10-05 2014-06-01 Univ China Medical 藥用載體及其製備方法與用途
JP6445453B2 (ja) * 2012-11-28 2018-12-26 ビクトリア リンク リミテッド 樹状コア化合物
US9707276B2 (en) 2012-12-03 2017-07-18 Merck Sharp & Dohme Corp. O-glycosylated carboxy terminal portion (CTP) peptide-based insulin and insulin analogues
US9725493B2 (en) * 2013-01-22 2017-08-08 Case Western Reserve University N-terminal truncated insulin analogues
KR20160065930A (ko) * 2013-10-04 2016-06-09 머크 샤프 앤드 돔 코포레이션 글루코스-반응성 인슐린 접합체
US20180110863A1 (en) * 2015-04-08 2018-04-26 Merck Sharp & Dohme Corp. Glucose-responsive insulin conjugates
CA3025988A1 (en) * 2016-06-02 2017-12-07 Sanofi Conjugates of a pharmaceutical agent and a moiety capable of binding to a glucose sensing protein
DK3570874T3 (da) 2017-01-17 2023-04-11 Univ Wayne State Zwitterionisk polymer-insulin-sammensætninger og dertil relaterede fremgangsmåder
CN110612305B (zh) 2017-03-23 2023-11-28 维多利亚林克有限公司 硫酸乙酰肝素糖模拟化合物及其医药与化妆品用途
WO2018175272A1 (en) 2017-03-23 2018-09-27 Merck Sharp & Dohme Corp. Glucose responsive insulin comprising a tri-valent sugar cluster for treatment of diabetes
CN111433193A (zh) 2017-12-01 2020-07-17 赛诺菲 药剂和能够结合至葡萄糖传感蛋白的部分的新型缀合物
EP3727424A4 (en) * 2017-12-18 2021-10-27 Merck Sharp & Dohme Corp. CONJUGATE-BASED SYSTEMS FOR CONTROLLED INSULIN RELEASE
CN108610494B (zh) * 2018-03-20 2020-11-06 南京理工大学 聚醚砜/功能性含糖聚合物杂化膜的制备方法
CN110146605A (zh) * 2019-04-19 2019-08-20 南通联亚药业有限公司 一种测定格列吡嗪原料药及其缓释片中特定基因毒性杂质的分析方法
EP3980052A4 (en) 2019-06-06 2023-08-23 Merck Sharp & Dohme LLC GLUCOSE-RESPONDING INSULIN CONJUGATES
CN113773400B (zh) * 2020-06-09 2023-08-18 宁波鲲鹏生物科技有限公司 一种门冬胰岛素衍生物及其应用
CN113773398B (zh) * 2020-06-10 2023-05-23 宁波鲲鹏生物科技有限公司 一种德谷胰岛素衍生物及其应用
CN112480184A (zh) * 2020-12-09 2021-03-12 上海应用技术大学 一种利用梯度点击化学合成含多种糖的树枝化糖胺的方法
WO2022234030A1 (en) 2021-05-05 2022-11-10 Novo Nordisk A/S Insulin on board for glucose sensitive insulin
WO2024096408A1 (ko) * 2022-11-01 2024-05-10 주식회사 삼양홀딩스 아마이드 및 에스터 작용기를 갖는 지질 및 이의 제조방법
CN120201998A (zh) * 2022-11-16 2025-06-24 三养控股公司 药物递送用纳米颗粒组合物

Family Cites Families (131)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US39055A (en) 1863-06-30 Improvement in churns
US3591574A (en) 1968-05-29 1971-07-06 American Home Prod Tri-n-phenylglycyl derivatives of insulin
DE1793517C3 (de) 1968-09-28 1974-12-05 Farbwerke Hoechst Ag, Vormals Meister Lucius & Bruening, 6000 Frankfurt N(Al),N(B29>Bis-(tert.-butyloxycarbonyl)-insulin und Verfahren zu seiner Herstellung
US3697502A (en) * 1969-11-03 1972-10-10 Christensen Henry M Method of making iron dextran-preparations
US3847890A (en) 1971-11-01 1974-11-12 A Green Acidic monosaccharide-substituted proteins
US4086257A (en) 1976-10-12 1978-04-25 Sears Barry D Phosphatidyl quaternary ammonium compounds
EP0009842B1 (en) 1978-10-02 1982-11-10 THE PROCTER & GAMBLE COMPANY Liposomes for drug delivery and composition containing a liposome drug system
US4377567A (en) 1978-10-02 1983-03-22 The Procter & Gamble Company Lipid membrane drug delivery
US4348387A (en) 1979-07-31 1982-09-07 The Rockefeller University Method and system for the controlled release of biologically active substances to a body fluid
US4421685A (en) 1980-03-27 1983-12-20 Eli Lilly And Company Process for producing an insulin
JPS608000B2 (ja) 1980-04-11 1985-02-28 呉羽化学工業株式会社 アミノフエニル誘導体及び該誘導体を含有する生理活性剤
US4435173A (en) 1982-03-05 1984-03-06 Delta Medical Industries Variable rate syringe pump for insulin delivery
US4498843A (en) 1982-08-02 1985-02-12 Schneider Philip H Insulin infusion pump
US4444683A (en) 1982-11-17 1984-04-24 University Of Utah Glycosylated insulin derivatives
US4603044A (en) 1983-01-06 1986-07-29 Technology Unlimited, Inc. Hepatocyte Directed Vesicle delivery system
EP0119650A3 (en) 1983-03-21 1987-09-30 THE PROCTER & GAMBLE COMPANY Galactosyl-insulin conjugates useful in treating diabetics
US4863896A (en) 1984-05-03 1989-09-05 Technology Unlimited, Inc. Diabetic control by combined insulin forms
DK160633C (da) 1985-05-15 1991-09-02 Henning Munk Ejlersen Slangepumpe, isaer til avendelse som insulinpumpe
US5239062A (en) * 1986-03-20 1993-08-24 Dana-Farber Cancer Institute, Inc. Blocked lectins, methods and affinity support for making same using affinity ligands, and method of killing selected cell populations having reduced nonselective cytotoxicity
US5395924A (en) 1986-03-20 1995-03-07 Dana-Farber Cancer Institute, Inc. Blocked lectins; methods and affinity support for making the same using affinity ligands; and method of killing selected cell populations having reduced non-selective cytotoxicity
US5527524A (en) 1986-08-18 1996-06-18 The Dow Chemical Company Dense star polymer conjugates
US4853218A (en) * 1987-02-24 1989-08-01 Schering Corporation Zinc-protamine-alpha interferon complex
US5062841A (en) 1988-08-12 1991-11-05 The Regents Of The University Of California Implantable, self-regulating mechanochemical insulin pump
DK111489D0 (da) 1989-03-08 1989-03-08 Novo Nordisk As Peptider
KR930001305B1 (ko) 1989-10-19 1993-02-25 니뽕 유우시 가부시끼가이샤 당 응답형 고분자 복합체(Polymer Complexes of Sugar Response Type)
IL99699A (en) * 1990-10-10 2002-04-21 Autoimmune Inc Drug with the option of oral, intra-intestinal, or inhaled dosing for suppression of autoimmune response associated with type I diabetes
RU2003351C1 (ru) * 1991-06-26 1993-11-30 Липов Борис Петрович; Сафронов Игорь Николаевич Инъектор
GB9200638D0 (en) 1992-01-10 1992-03-11 Leicester Polytechnic Drug system
EP0585436B1 (en) 1992-02-13 2000-05-03 SurModics, Inc. Immobilization of chemical species in crosslinked matrices
GB9316895D0 (en) 1993-08-13 1993-09-29 Guy S And St Thomas Hospitals Hepatoselective insulin analogues
GB9313484D0 (en) 1993-06-30 1993-08-11 Univ Montfort Drug system ii
US6342225B1 (en) 1993-08-13 2002-01-29 Deutshces Wollforschungsinstitut Pharmaceutical active conjugates
US6869930B1 (en) 1993-09-17 2005-03-22 Novo Nordisk A/S Acylated insulin
US6011007A (en) 1993-09-17 2000-01-04 Novo Nordisk A/S Acylated insulin
EP1132404A3 (en) * 1993-09-17 2002-03-27 Novo Nordisk A/S Acylated insulin
US5461031A (en) 1994-06-16 1995-10-24 Eli Lilly And Company Monomeric insulin analog formulations
US5474978A (en) 1994-06-16 1995-12-12 Eli Lilly And Company Insulin analog formulations
US5504188A (en) 1994-06-16 1996-04-02 Eli Lilly And Company Preparation of stable zinc insulin analog crystals
US6500645B1 (en) 1994-06-17 2002-12-31 Novo Nordisk A/S N-terminally extended proteins expressed in yeast
US5547929A (en) 1994-09-12 1996-08-20 Eli Lilly And Company Insulin analog formulations
US5693609A (en) 1994-11-17 1997-12-02 Eli Lilly And Company Acylated insulin analogs
YU18596A (sh) 1995-03-31 1998-07-10 Eli Lilly And Company Analogne formulacije monomernog insulina
US5902603A (en) 1995-09-14 1999-05-11 Cygnus, Inc. Polyurethane hydrogel drug reservoirs for use in transdermal drug delivery systems, and associated methods of manufacture and use
CN1120707C (zh) 1995-11-22 2003-09-10 约翰斯·霍普金斯大学 增强生物分子的细胞摄取的配体
US5723589A (en) 1995-12-21 1998-03-03 Icn Pharmaceuticals Carbohydrate conjugated bio-active compounds
US5866538A (en) 1996-06-20 1999-02-02 Novo Nordisk A/S Insulin preparations containing NaCl
US5948751A (en) 1996-06-20 1999-09-07 Novo Nordisk A/S X14-mannitol
US5905140A (en) 1996-07-11 1999-05-18 Novo Nordisk A/S, Novo Alle Selective acylation method
EP0954589A1 (en) 1997-01-24 1999-11-10 Novo Nordisk A/S Synthetic leader peptide sequences
AR012894A1 (es) 1997-06-13 2000-11-22 Lilly Co Eli Formulacion de insulina en solucion estable, su uso para preparar un medicamento y proceso para la preparacion de la misma.
US6444641B1 (en) 1997-10-24 2002-09-03 Eli Lilly Company Fatty acid-acylated insulin analogs
JP2001521006A (ja) 1997-10-24 2001-11-06 イーライ・リリー・アンド・カンパニー 不溶性インシュリン組成物
ZA989744B (en) 1997-10-31 2000-04-26 Lilly Co Eli Method for administering acylated insulin.
WO1999034821A1 (en) 1998-01-09 1999-07-15 Novo Nordisk A/S Stabilised insulin compositions
ES2245824T3 (es) 1998-04-15 2006-01-16 Novo Nordisk A/S Nuevo proceso de separacion de proteinas utilizando un eluyente que contiene ca++.
US6300319B1 (en) * 1998-06-16 2001-10-09 Isis Pharmaceuticals, Inc. Targeted oligonucleotide conjugates
US6844166B1 (en) 1998-09-11 2005-01-18 Sensor Technologies Inc. Recombinant reduced valency carbohydrate binding ligands
US6323311B1 (en) 1999-09-22 2001-11-27 University Of Utah Research Foundation Synthesis of insulin derivatives
US6777207B2 (en) 1999-12-29 2004-08-17 Novo Nordisk A/S Method for making insulin precursors and insulin precursor analogues having improved fermentation yield in yeast
US6521738B2 (en) 1999-12-29 2003-02-18 Novo Nordisk A/S Method for making insulin precursors and insulin precursor analogs
US7316999B2 (en) 2000-06-02 2008-01-08 Novo Nordisk A/S Glucose dependent release of insulin from glucose sensing insulin derivatives
JP2003535106A (ja) * 2000-06-02 2003-11-25 ノボ ノルディスク アクティーゼルスカブ グルコース検知性インスリン誘導体からの、インスリンのグルコース依存性放出
US6650951B1 (en) 2000-06-19 2003-11-18 International Business Machines Corporation Method and insulin pump for providing a forgotten bolus warning
CA2419156A1 (en) 2000-07-13 2002-01-24 The Ohio State University Research Foundation Multimeric biopolymers as structural elements, sensors and actuators in microsystems
US7060675B2 (en) 2001-02-15 2006-06-13 Nobex Corporation Methods of treating diabetes mellitus
WO2003047462A1 (en) 2001-03-12 2003-06-12 Clemson University Polysaccharide-based polmerizable hydrogels
US7105314B2 (en) 2001-04-02 2006-09-12 Novo Nordisk A/S Method for making human insulin precursors
ES2411007T3 (es) * 2001-10-10 2013-07-04 Novo Nordisk A/S Remodelación y glicoconjugación de péptidos
US7311892B2 (en) 2001-10-26 2007-12-25 The Uab Research Foundation Multidrug multiligand conjugates for targeted drug delivery
US6736796B2 (en) 2001-11-26 2004-05-18 Nili-Med Ltd. Fluid drug delivery device
US7473680B2 (en) * 2001-11-28 2009-01-06 Neose Technologies, Inc. Remodeling and glycoconjugation of peptides
EP1453860A2 (en) * 2001-12-02 2004-09-08 Novo Nordisk A/S Novel glucose-dependant insulins
US7317000B2 (en) 2001-12-02 2008-01-08 Novo Nordisk A/S Glucose-dependent insulins
WO2003048915A1 (en) 2001-12-07 2003-06-12 Ntt Docomo, Inc. Mobile communication terminal, method for controlling execution state of application program, application program, and recording medium wherein application program has been recorded
US6852104B2 (en) 2002-02-28 2005-02-08 Smiths Medical Md, Inc. Programmable insulin pump
US6744350B2 (en) 2002-02-28 2004-06-01 Smiths Medical Md, Inc. Insulin pump having missed meal bolus alarm
DE10209821A1 (de) 2002-03-06 2003-09-25 Biotechnologie Ges Mittelhesse Kopplung von Proteinen an ein modifiziertes Polysaccharid
JP5599543B2 (ja) 2002-05-07 2014-10-01 ノヴォ ノルディスク アー／エス 単量体インスリン及びアシル化インスリンを含む可溶性製剤
WO2004009665A2 (en) * 2002-07-19 2004-01-29 The Regents Of The University Of California Dendrimers as molecular translocators
US7993108B2 (en) 2002-10-09 2011-08-09 Abbott Diabetes Care Inc. Variable volume, shape memory actuated insulin dispensing pump
AU2002368314A1 (en) * 2002-10-29 2004-05-25 Ranbaxy Laboratories Limited Iminosugar derivatives as glucosidase inhibitors
CA2509382A1 (en) * 2002-12-17 2004-07-08 Todd C. Zion Stimuli-responsive systems for controlled drug delivery
WO2004057002A2 (en) 2002-12-20 2004-07-08 Greenovation Biotech Gmbh Production of heterologous glycosylated proteins in bryophyte cells
WO2004101619A1 (ja) * 2003-05-15 2004-11-25 Shionogi Co., Ltd. 機能的糖ペプチドの合理的設計および合成
EP1687428A1 (en) 2003-11-14 2006-08-09 Novo Nordisk A/S Processes for making acylated insulin
WO2006088473A2 (en) 2004-04-23 2006-08-24 Panduranga Rao Koritala Microcapsules and nanocapsules for the transmucosal delivery of therapeutic and diagnostic agents
WO2006008238A1 (en) 2004-07-16 2006-01-26 Novo Nordisk A/S Method for selective acylation
RU2527893C2 (ru) 2004-07-19 2014-09-10 Биокон Лимитед Инсулин-олигомерные конъюгаты, их препараты и применения
WO2006062685A2 (en) * 2004-11-11 2006-06-15 Affymax, Inc. Novel peptides that bind to the erythropoietin receptor
TWI376234B (en) 2005-02-01 2012-11-11 Msd Oss Bv Conjugates of a polypeptide and an oligosaccharide
US20060247154A1 (en) 2005-02-24 2006-11-02 Lifescan, Inc. Concanavalin a, methods of expressing, purifying and characterizing concanavalina, and sensors including the same
US20070207498A1 (en) 2005-02-24 2007-09-06 Lifescan, Inc. Design and construction of dimeric concanavalin a mutants
WO2006102762A1 (en) 2005-04-01 2006-10-05 Mcmaster University Glucose responsive microgels
KR101487027B1 (ko) 2005-09-30 2015-01-28 미카나 테라퓨틱스, 인크. 치환된 피라졸 화합물
JP2009511544A (ja) 2005-10-10 2009-03-19 ナームローゼ・フエンノートチヤツプ・オルガノン 抗血栓化合物
US7517856B2 (en) 2005-10-11 2009-04-14 Ben-Gurion University Of The Negev Research And Development Authority Bioconjugates comprising sulfated polysaccharides and their uses
US7687608B2 (en) 2005-10-19 2010-03-30 Smartcells, Inc. Methods for reducing the mitogenicity of lectin compositions
DE602007009496D1 (de) 2006-02-27 2010-11-11 Novo Nordisk As Insulinderivate
EP2043689A4 (en) 2006-07-24 2013-08-07 Univ Duke ACTIVE ADMINISTRATION WITH STIMULUS-REPONSIVE BIOPOLYMERS
US8299015B2 (en) 2006-07-25 2012-10-30 Lipoxen Technologies Limited Derivatisation of granulocyte colony-stimulating factor
FR2904315B1 (fr) 2006-07-26 2012-12-14 Centre Nat Rech Scient Composes pyridaziniques et pyrroliques, procedes d'obtention et applications
US7515060B2 (en) 2006-10-17 2009-04-07 Smiths Medical Md, Inc. Insulin pump for the visually impaired
US20080172028A1 (en) 2006-10-17 2008-07-17 Blomquist Michael L Insulin pump having selectable insulin absorption models
CN101273961A (zh) 2007-03-30 2008-10-01 中国人民解放军总医院 葡萄糖敏感水凝胶
US20090053167A1 (en) 2007-05-14 2009-02-26 Neose Technologies, Inc. C-, S- and N-glycosylation of peptides
US20090005726A1 (en) 2007-06-27 2009-01-01 Steven Paul Jones Insulin Pump Having Expected Bolus Interval and an Early Bolus Interval
WO2009033588A2 (en) 2007-09-11 2009-03-19 F. Hoffmann-La-Roche Ag Self-controlled insulin delivery system
WO2009059450A1 (en) 2007-11-05 2009-05-14 Shanghai Jiaotong University Peptide ligand directed drug delivery
GB2446247B (en) 2007-11-27 2008-12-17 Robert Joseph Wagener Homeostatic insulin pump
CA2711503A1 (en) 2008-01-08 2009-07-16 Biogenerix Ag Glycoconjugation of polypeptides using oligosaccharyltransferases
US20090177154A1 (en) 2008-01-08 2009-07-09 Michael Blomquist Insulin pump with convenience features
US20090177142A1 (en) 2008-01-09 2009-07-09 Smiths Medical Md, Inc Insulin pump with add-on modules
RU2381238C2 (ru) 2008-01-31 2010-02-10 Ордена Трудового Красного Знамени Институт нефтехимического синтеза им. А.В. Топчиева Российской академии наук (статус государственного учреждения) Способ получения глюкозочувствительных полимерных гидрогелей
RU2495131C2 (ru) 2008-02-19 2013-10-10 Байокон Лимитид Способ получения рекомбинантного инсулина гларгина
EP2141620B1 (de) 2008-07-01 2018-10-31 Roche Diabetes Care GmbH Insulinpumpe und Verfahren zur Steuerung einer Benutzerschnittstelle einer Insulinpumpe
WO2010088300A1 (en) * 2009-01-28 2010-08-05 Smartcells, Inc. Crystalline insulin-conjugates
BRPI1007457A2 (pt) * 2009-01-28 2015-08-25 Smartcells Inc Conjungado, formulação de liberação prolongada, e, sistema de distribuição de bomba.
WO2010088268A1 (en) * 2009-01-28 2010-08-05 Smartcells, Inc. Exogenously triggered controlled release materials and uses thereof
WO2010088286A1 (en) * 2009-01-28 2010-08-05 Smartcells, Inc. Synthetic conjugates and uses thereof
WO2010088276A2 (en) * 2009-01-28 2010-08-05 Smartcells, Inc. Polynucleotide aptamer-based cross -linked materials and uses thereof
EP2391215A4 (en) * 2009-01-28 2013-10-30 Smartcells Inc BINDING CENTER MODIFIED LECTINS AND THEIR USE
WO2010107520A1 (en) * 2009-03-20 2010-09-23 Smartcells, Inc. Soluble non-depot insulin conjugates and uses thereof
US9095623B2 (en) * 2009-03-20 2015-08-04 Smartcells, Inc. Terminally-functionalized conjugates and uses thereof
US8623345B2 (en) * 2009-03-20 2014-01-07 Smartcells Terminally-functionalized conjugates and uses thereof
EP2448962B1 (en) 2009-06-30 2016-10-19 Novo Nordisk A/S Insulin derivatives
EP2598522A4 (en) * 2010-07-28 2014-11-12 Smartcells Inc RECOMBINANT LKTINE, BINDING POINT MODIFIED LECTIN AND APPLICATIONS THEREOF
AU2011282983A1 (en) * 2010-07-28 2013-02-21 Smartcells, Inc. Drug-ligand conjugates, synthesis thereof, and intermediates thereto
JP2013535467A (ja) * 2010-07-28 2013-09-12 スマートセルズ・インコーポレイテツド 組換えにより発現されたインスリンポリペプチドおよびその使用
KR20160065930A (ko) * 2013-10-04 2016-06-09 머크 샤프 앤드 돔 코포레이션 글루코스-반응성 인슐린 접합체
US20180110863A1 (en) * 2015-04-08 2018-04-26 Merck Sharp & Dohme Corp. Glucose-responsive insulin conjugates
US9899205B2 (en) * 2016-05-25 2018-02-20 Kla-Tencor Corporation System and method for inhibiting VUV radiative emission of a laser-sustained plasma source

Also Published As

Publication number Publication date
US20140274888A1 (en) 2014-09-18
AU2010208313A8 (en) 2015-12-17
MA33064B1 (fr) 2012-02-01
US10398781B2 (en) 2019-09-03
EA027757B1 (ru) 2017-08-31
US9265838B2 (en) 2016-02-23
BRPI1007457A2 (pt) 2015-08-25
AU2015202871B2 (en) 2017-08-17
KR20110104081A (ko) 2011-09-21
SG2014006597A (en) 2014-04-28
JP2014139215A (ja) 2014-07-31
AU2015202871A1 (en) 2015-06-18
NZ594248A (en) 2015-03-27
JP2012516341A (ja) 2012-07-19
JP5834103B2 (ja) 2015-12-16
AU2010208313B2 (en) 2015-07-23
JP2016065072A (ja) 2016-04-28
CA2932926C (en) 2018-12-18
CA2932926A1 (en) 2010-08-05
TN2011000354A1 (en) 2013-03-27
US20110301083A1 (en) 2011-12-08
SG173112A1 (en) 2011-08-29
JP6040301B2 (ja) 2016-12-07
CN102365025A (zh) 2012-02-29
AU2015202872A1 (en) 2015-06-18
AU2015202872B2 (en) 2017-05-25
NI201100150A (es) 2011-11-09
PE20120583A1 (es) 2012-05-19
EP2391218A1 (en) 2011-12-07
CA2750262C (en) 2016-08-09
US20160193351A1 (en) 2016-07-07
CO6400173A2 (es) 2012-03-15
GT201100208A (es) 2014-02-10
WO2010088294A1 (en) 2010-08-05
IL214099A0 (en) 2011-08-31
EP2391218A4 (en) 2015-05-13
SG193837A1 (en) 2013-10-30
CN105753965A (zh) 2016-07-13
US9050370B2 (en) 2015-06-09
AU2010208313A1 (en) 2011-09-01
US9579391B2 (en) 2017-02-28
ES2791683T3 (es) 2020-11-05
EP2391218B1 (en) 2020-03-18
DOP2011000244A (es) 2011-10-15
JP5508438B2 (ja) 2014-05-28
MX2011007929A (es) 2011-08-17
US20180064824A1 (en) 2018-03-08
KR20140012219A (ko) 2014-01-29
EA201170986A1 (ru) 2012-03-30
KR101635689B1 (ko) 2016-07-01
US20150265717A1 (en) 2015-09-24
CA2750262A1 (en) 2010-08-05
CR20110408A (es) 2011-12-08

Similar Documents

Publication Publication Date Title
ECSP11011240A (es) Conjugados de insulina cristalina
Ma et al. Photovoltaically top-performing perovskite crystal facets
Jeitschko The crystal structure of Fe2AlB2
UY29060A1 (es) Solución para infusión de dihidropteridinonas estabilizada para el almacenamiento
MX346145B (es) Composición de sistema de suministro de arnsi in vivo basado en péptidos.
He et al. Perovskite spin light-emitting diodes with simultaneously high electroluminescence dissymmetry and high external quantum efficiency
CN107556966B (zh) 紫外光吸收胶与柔性oled显示面板及其制作方法
BR112012018116A2 (pt) "hormônios do crescimento com eficácia in vivo prolongada"
Li et al. Effects of polymorphic DNA on the fluorescent properties of silver nanoclusters
Zhang et al. Thickness-controlled wafer-scale single-crystalline MAPbBr3 films epitaxially grown on CsPbBr3 substrates by the droplet-evaporated crystallization method
Jia et al. Upconversion luminescence from Ln3+ (Ho3+, Pr3+) ion-doped BaCl2 particles via NIR light of sun excitation
MX2021009921A (es) Preformulacion de lipidos de liberacion sostenida y composicion farmacetica de liberacion sostenida inyectable en la forma de una solucion de lipidos que contiene a la misma.
Yuan et al. Purely organic optoelectronic materials with ultralong-lived excited states under ambient conditions
Zhang et al. Synergistic photoluminescence enhancement in nonaromatic amino acids and sugars via glycosylation
PE20140860A1 (es) Compuestos de pirazol como antagonistas de crth2
AR052090A1 (es) Procedimiento para manufacturar un sacarido cristalino eutectico polvo de hidrolizado de almidon hidrogenado y compuesto que contiene dicho sacarido cristalino eutectico
CN104649923B (zh) 1-氨基-12-羟基-3,4,9,10-苝四羧酸正丁酯及其合成方法
BR112014013906A2 (pt) ésteres de fosfato aromáticos como componentes de formulação agroquímica
MD4484B1 (ro) Forma cristalină VIII a agomelatinei, procedeu de preparare, utilizarea acesteia şi compoziţie farmaceutică care o conţine
Mondal et al. Excited-state proton transfer from pyranine to acetate in methanol
PE20131327A1 (es) Forma cristalina delta de la sal de arginina de perindoprilo, su procedimiento de preparacion, y las composiciones farmaceuticas que la contienen
JP5858274B2 (ja) 結晶化促進方法、結晶化解析方法、結晶の製造方法、結晶化装置の制御プログラム、記録媒体、及び結晶化装置
Fan et al. Facile Uniaxial Electrospinning Strategy To Embed CsPbBr3 Nanocrystals with Enhanced Water/Thermal Stabilities for Reversible Fluorescence Switches
CN104194770A (zh) 一种具有紫色发光性能的荧光材料及其制备方法
Stella et al. Phenylbutazone ionization kinetics