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

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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)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (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)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Hematology (AREA)
  • Biophysics (AREA)
  • Obesity (AREA)
  • Genetics & Genomics (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) 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) SG173112A1 (es)
TN (1) TN2011000354A1 (es)
WO (1) WO2010088294A1 (es)

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