ES2527608T3 - Composición farmacéutica que contiene un vehículo de oxígeno estable a temperatura elevada - Google Patents

Composición farmacéutica que contiene un vehículo de oxígeno estable a temperatura elevada Download PDF

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ES2527608T3
ES2527608T3 ES11746429.7T ES11746429T ES2527608T3 ES 2527608 T3 ES2527608 T3 ES 2527608T3 ES 11746429 T ES11746429 T ES 11746429T ES 2527608 T3 ES2527608 T3 ES 2527608T3
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hemoglobin
low
erythrocytes
remove
solution
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Bing Lou Wong
Sui Yi Kwok
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FIRST GAIN INTERNAT Ltd
FIRST GAIN INTERNATIONAL Ltd
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FIRST GAIN INTERNAT Ltd
FIRST GAIN INTERNATIONAL Ltd
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Priority claimed from US13/013,847 external-priority patent/US8742073B2/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/41Porphyrin- or corrin-ring-containing peptides
    • A61K38/42Haemoglobins; Myoglobins
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/795Porphyrin- or corrin-ring-containing peptides
    • C07K14/805Haemoglobins; Myoglobins
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/12Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00General protective or antinoxious agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/06Antianaemics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00Drugs for disorders of the blood or the extracellular fluid
    • A61P7/08Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Urology & Nephrology (AREA)
  • Heart & Thoracic Surgery (AREA)
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  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

Método para la preparación de una composición farmacéutica que contiene un vehículo de oxígeno altamente purificada y estable a temperatura elevada, incluyendo la composición farmacéutica que contiene un vehículo de oxígeno hemoglobina tetramérica reticulada no polimérica, y comprendiendo el método las etapas siguientes: a) proporcionar sangre completa de mamífero que incluye al menos eritrocitos y plasma; b) separar los eritrocitos del plasma en la sangre completa de mamífero; c) filtrar los eritrocitos que se separaron del plasma para obtener una fracción de eritrocitos filtrados; d) lavar la fracción de eritrocitos filtrados para eliminar las impurezas proteínicas plasmáticas, dando como resultado eritrocitos lavados; e) disgregar los eritrocitos lavados mediante una lisis hipotónica controlada durante un tiempo suficiente para lisar los eritrocitos sin lisar los leucocitos en un aparato de citólisis instantánea a un caudal de 50-1000 litro/h para crear una disolución que comprende un lisado de eritrocitos disgregados; f) llevar a cabo una filtración para eliminar al menos una porción del retenido de desecho del lisado; g) extraer una primera disolución de hemoglobina del lisado; h) llevar a cabo un primer procedimiento de ultrafiltración utilizando un filtro de ultrafiltración configurado para eliminar las impurezas que presentan un peso molecular mayor que la hemoglobina tetramérica para eliminar además cualquier virus y retenido de desecho residual de la primera disolución de hemoglobina para obtener una segunda disolución de hemoglobina; i) llevar a cabo una cromatografía en columna de flujo continuo sobre la segunda disolución de hemoglobina para eliminar los fosfolípidos, las impurezas proteínicas y la hemoglobina dimérica y para formar una disolución de hemoglobina exenta de fosfolípidos, baja en impurezas proteínicas y baja en dímeros; j) llevar a cabo un segundo procedimiento de ultrafiltración sobre la disolución de hemoglobina exenta de fosfolípidos, baja en impurezas proteínicas y baja en dímeros utilizando un filtro configurado para eliminar las impurezas, dando como resultado una disolución de hemoglobina purificada concentrada exenta de fosfolípidos, baja en impurezas proteínicas y baja en dímeros; k) bloquear los grupos sulfhidrilo de las moléculas de hemoglobina en la disolución de hemoglobina purificada concentrada exenta de fosfolípidos baja en impurezas proteínicas y baja en dímeros mediante un reactivo de sulfhidrilo en un entorno completamente oxigenado de manera que las moléculas de hemoglobina presenten cada una al menos un resto de cisteína que incluye un grupo protector de tiol de manera que las moléculas de hemoglobina no puedan unirse al factor relajante derivado del endotelio en el sitio de cisteína; l) reticular la hemoglobina tiol protegida mediante fumarato de bis-3,5-dibromosalicilo (DBSF) con una relación molar de la hemoglobina tiol protegida a DBSF mayor que 1:2,5 a menor que 1:5,0 en un entorno desoxigenado para formar hemoglobina tetramérica reticulada estable a temperatura elevada sin la formación de hemoglobina polimérica, de manera que el peso molecular de la hemoglobina tetramérica reticulada resultante es 60-70 kDa y consiste esencialmente en hemoglobina tetramérica reticulada no polimérica; m) intercambiar un tampón fisiológico adecuado por la hemoglobina tetramérica reticulada; n) eliminar cualquier hemoglobina tetramérica no reticulada residual y cualesquiera sustancias químicas residuales mediante lavado; o) añadir N-acetilcisteína a una concentración de 0,2-0,4% a la hemoglobina tetramérica reticulada para mantener un nivel de metahemoglobina inferior a 5%; y p) añadir la hemoglobina tetramérica reticulada baja en dímeros, exenta de fosfolípidos, tiol protegida, estable a temperatura elevada hasta una temperatura de 80ºC, libre de hemoglobina polimérica, a un vehículo farmacéuticamente aceptable

Description

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Claims (1)

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ES11746429.7T 2010-05-27 2011-04-15 Composición farmacéutica que contiene un vehículo de oxígeno estable a temperatura elevada Active ES2527608T3 (es)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US348764P 2002-01-14
US34876410P 2010-05-27 2010-05-27
US13/013,847 US8742073B2 (en) 2010-05-27 2011-01-26 Method for the preparation of a high-temperature stable oxygen-carrier-containing pharmaceutical composition and the use thereof
US201113013847 2011-01-26
US201113083639 2011-04-11
US13/083,639 US7989593B1 (en) 2010-05-27 2011-04-11 Method for the preparation of a high-temperature stable oxygen-carrier-containing pharmaceutical composition and the use thereof
PCT/US2011/032594 WO2011149602A1 (en) 2010-05-27 2011-04-15 High-temperature stable oxygen-carrier-containing pharmaceutical composition

Publications (1)

Publication Number Publication Date
ES2527608T3 true ES2527608T3 (es) 2015-01-27

Family

ID=44314337

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Application Number Title Priority Date Filing Date
ES11746429.7T Active ES2527608T3 (es) 2010-05-27 2011-04-15 Composición farmacéutica que contiene un vehículo de oxígeno estable a temperatura elevada

Country Status (20)

Country Link
US (1) US7989593B1 (es)
EP (1) EP2411025B1 (es)
JP (1) JP5261806B2 (es)
KR (1) KR101185437B1 (es)
CN (2) CN102405051B (es)
AR (1) AR081222A1 (es)
AU (1) AU2011221433B2 (es)
CA (1) CA2752943C (es)
CY (1) CY1115986T1 (es)
DK (1) DK2411025T3 (es)
ES (1) ES2527608T3 (es)
NZ (1) NZ594915A (es)
PL (1) PL2411025T3 (es)
PT (1) PT2411025E (es)
RU (1) RU2475252C1 (es)
SA (1) SA111320476B1 (es)
SG (1) SG182237A1 (es)
TW (1) TWI377947B (es)
WO (1) WO2011149602A1 (es)
ZA (1) ZA201208726B (es)

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