ECSP11011240A - Conjugados de insulina cristalina - Google Patents
Conjugados de insulina cristalinaInfo
- 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
Links
Classifications
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- 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
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- 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
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- 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)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Diabetes (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Endocrinology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Genetics & Genomics (AREA)
- Biophysics (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.
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) | CN102365025A (es) |
AU (2) | AU2015202872B2 (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) | SG2014006597A (es) |
TN (1) | TN2011000354A1 (es) |
WO (1) | WO2010088294A1 (es) |
Families Citing this family (28)
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JP2012516340A (ja) | 2009-01-28 | 2012-07-19 | スマートセルズ・インコーポレイテツド | 合成コンジュゲートおよびその使用 |
CA2932926C (en) * | 2009-01-28 | 2018-12-18 | Smartcells, Inc. | Conjugate based systems for controlled drug delivery |
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 |
WO2012015691A2 (en) | 2010-07-28 | 2012-02-02 | Smartcells, Inc. | Recombinant lectins, binding-site modified lectins and uses thereof |
US20130131310A1 (en) * | 2010-07-28 | 2013-05-23 | John Kane | Drug-ligand conjugates, synthesis thereof, and intermediates thereto |
WO2012015692A2 (en) | 2010-07-28 | 2012-02-02 | Smartcells, Inc. | Recombinantly expressed insulin polypeptides and uses thereof |
WO2012015681A2 (en) | 2010-07-28 | 2012-02-02 | Smartcells, Inc. | Drug-ligand conjugates, synthesis thereof, and intermediates thereto |
US20130302825A1 (en) * | 2010-10-14 | 2013-11-14 | Merck | 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 |
CN104981455B (zh) * | 2012-11-28 | 2019-04-19 | 维多利亚林克有限公司 | 树枝状核心化合物 |
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CN105142660A (zh) * | 2013-01-22 | 2015-12-09 | 卡斯西部储备大学 | N末端截短的胰岛素类似物 |
AR097893A1 (es) * | 2013-10-04 | 2016-04-20 | Merck Sharp & Dohme | Conjugados de insulina sensibles a glucosa |
WO2016164288A1 (en) * | 2015-04-08 | 2016-10-13 | Merck Sharp & Dohme Corp. | Glucose-responsive insulin conjugates |
CN109562185A (zh) | 2016-06-02 | 2019-04-02 | 赛诺菲 | 药剂与能够结合葡萄糖感应蛋白的部分的新颖缀合物 |
EP3570874B1 (en) * | 2017-01-17 | 2023-03-08 | Wayne State University | Zwitterionic polymer-insulin compositions and related methods |
EP3600381A4 (en) * | 2017-03-23 | 2021-06-16 | Merck Sharp & Dohme Corp. | GLUCOSE-ACTIVE INSULIN WITH A THREE-VALUE SUGAR CLUSTER FOR THE TREATMENT OF DIABETES |
AU2017405304B2 (en) * | 2017-03-23 | 2022-03-03 | Victoria Link Limited | Heparan sulfate glycomimetic compounds and their pharmaceutical and cosmeceutical uses |
EP3717463A1 (en) | 2017-12-01 | 2020-10-07 | Sanofi | Novel conjugates of a pharmaceutical agent and a moiety capable of binding to a glucose sensing protein |
US11820805B2 (en) * | 2017-12-18 | 2023-11-21 | Merck Sharp & Dohme Llc | Conjugate based systems for controlled insulin delivery |
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 |
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 |
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