ES2487633T3 - Métodos y composiciones para prevenir o tratar condiciones oftálmicas - Google Patents

Métodos y composiciones para prevenir o tratar condiciones oftálmicas Download PDF

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Publication number
ES2487633T3
ES2487633T3 ES10812524.6T ES10812524T ES2487633T3 ES 2487633 T3 ES2487633 T3 ES 2487633T3 ES 10812524 T ES10812524 T ES 10812524T ES 2487633 T3 ES2487633 T3 ES 2487633T3
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arg
dmt
phe
lys
tyr
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Liping Liu
Shibo Tang
Xiaoling Liang
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Stealth Peptides International Inc
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Stealth Peptides International Inc
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/06—Tripeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/07—Tetrapeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/12—Ophthalmic agents for cataracts
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/08—Tripeptides
    • C07K5/0815—Tripeptides with the first amino acid being basic
    • C07K5/0817—Tripeptides with the first amino acid being basic the first amino acid being Arg
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C07K5/1002—Tetrapeptides with the first amino acid being neutral
    • C07K5/1016—Tetrapeptides with the first amino acid being neutral and aromatic or cycloaliphatic

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

Abstract

Un péptido representado por la fórmula D-Arg-2'6'-Dmt-Lys-Phe-NH2 o Phe-D-Arg- Phe-Lys-NH2 para utilizar en el tratamiento o prevención de una condición oftalmológica en donde la condición oftalmológica se selecciona del grupo que consiste de: retinitis pigmentosa, neovascularización coroidea, y retinopatía inducida por el oxígeno.

Description

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E10812524
30-07-2014
TABLA 5. Análogos de péptidos con Actividad Mu-Opioide
Posición del Aminoácido 1
Posición del Aminoácido 2 Posición del Aminoácido 3 Posición del Aminoácido 4 Modificación terminal C
Tyr
D-Arg Phe Lys NH2
Tyr
D-Arg Phe Orn NH2
Tyr
D-Arg Phe Dab NH2
Tyr
D-Arg Phe Dap NH2
2’6’Dmt
D-Arg Phe Lys NH2
2’6’Dmt
D-Arg Phe Lys-NH(CH2)2-NH-dns NH2
2’6’Dmt
D-Arg Phe Lys-NH(CH2)2-NH-atn NH2
2’6’Dmt
D-Arg Phe dnsLys NH2
2’6’Dmt
D-Cit Phe Lys NH2
2’6’Dmt
D-Cit Phe Ahp NH2
2’6’Dmt
D-Arg Phe Orn NH2
2’6’Dmt
D-Arg Phe Dab NH2
2’6’Dmt
D-Arg Phe Dap NH2
2’6’Dmt
D-Arg Phe Ahp(ácido 2aminoheptanoico) NH2
Bio-2’6’Dmt
D-Arg Phe Lys NH2
3’5’Dmt
D-Arg Phe Lys NH2
3’5’Dmt
D-Arg Phe Orn NH2
3’5’Dmt
D-Arg Phe Dab NH2
3’5’Dmt
D-Arg Phe Dap NH2
Tyr
D-Arg Tyr Lys NH2
Tyr
D-Arg Tyr Orn NH2
Tyr
D-Arg Tyr Dab NH2
Tyr
D-Arg Tyr Dap NH2
2’6’Dmt
D-Arg Tyr Lys NH2
2’6’Dmt
D-Arg Tyr Orn NH2
2’6’Dmt
D-Arg Tyr Dab NH2
16
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2’6’Dmt
D-Arg Tyr Dap NH2
2’6’Dmt
D-Arg 2’6’Dmt Lys NH2
2’6’Dmt
D-Arg 2’6’Dmt Orn NH2
2’6’Dmt
D-Arg 2’6’Dmt Dab NH2
2’6’Dmt
D-Arg 2’6’Dmt Dap NH2
3’5’Dmt
D-Arg 3’5’Dmt Arg NH2
3’5’Dmt
D-Arg 3’5’Dmt Lys NH2
3’5’Dmt
D-Arg 3’5’Dmt Orn NH2
3’5’Dmt
D-Arg 3’5’Dmt Dab NH2
Tyr
D-Lys Phe Dap NH2
Tyr
D-Lys Phe Arg NH2
Tyr
D-Lys Phe Lys NH2
Tyr
D-Lys Phe Orn NH2
2’6’Dmt
D-Lys Phe Dab NH2
2’6’Dmt
D-Lys Phe Dap NH2
2’6’Dmt
D-Lys Phe Arg NH2
2’6’Dmt
D-Lys Phe Lys NH2
3’5’Dmt
D-Lys Phe Orn NH2
3’5’Dmt
D-Lys Phe Dab NH2
3’5’Dmt
D-Lys Phe Dap NH2
3’5’Dmt
D-Lys Phe Arg NH2
Tyr
D-Lys Tyr Lys NH2
Tyr
D-Lys Tyr Orn NH2
Tyr
D-Lys Tyr Dab NH2
Tyr
D-Lys Tyr Dap NH2
2’6’Dmt
D-Lys Tvr Lys NH2
2’6’Dmt
D-Lys Tyr Orn NH2
2’6’Dmt
D-Lys Tyr Dab NH2
2’6’Dmt
D-Lys Tyr Dap NH2
17
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2’6’Dmt
D-Lys 2’6’Dmt Lys NH2
2’6’Dmt
D-Lys 2’6’Dmt Orn NH2
2’6’Dmt
D-Lys 2’6’Dmt Dab NH2
2’6’Dmt
D-Lys 2’6’Dmt Dap NH2
2’6’Dmt
D-Arg Phe dnsDap NH2
2’6’Dmt
D-Arg Phe atnDap NH2
3’5’Dmt
D-Lys 3’5’Dmt Lys NH2
3’5’Dmt
D-Lys 3’5’Dmt Orn NH2
3’5’Dmt
D-Lys 3’5’Dmt Dab NH2
3’5’Dmt
D-Lys 3’5’Dmt Dap NH2
Tyr
D-Lys Phe Arg NH2
Tyr
D-Orn Phe Arg NH2
Tyr
D-Dab Phe Arg NH2
Tyr
D-Dap Phe Arg NH2
2’6’Dmt
D-Arg Phe Arg NH2
2’6’Dmt
D-Lvs Phe Arg NH2
2’6’Dmt
D-Orn Phe Arg NH2
2’6’Dmt
D-Dab Phe Arg NH2
3’5’Dmt
D-Dap Phe Arg NH2
3’5’Dmt
D-Arg Phe Arg NH2
3’5’Dmt
D-Lys Phe Arg NH2
3’5’Dmt
D-Orn Phe Arg NH2
Tyr
D-Lys Tyr Arg NH2
Tyr
D-Orn Tyr Arg NH2
Tyr
D-Dab Tyr Arg NH2
Tyr
D-Dap Tyr Arg NH2
2’6’Dmt
D-Arg 2’6’Dmt Arg NH2
2’6’Dmt
D-Lys 2’6’Dmt Arg NH2
2’6’Dmt
D-Orn 2’6’Dmt Arg NH2
18
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2’6’Dmt
D-Dab 2’6’Dmt Arg NH2
3’5’Dmt
D-Dap 3’5’Dmt Arg NH2
3’5’Dmt
D-Arg 3’5’Dmt Arg NH2
3’5’Dmt
D-Lys 3’5’Dmt Arg NH2
3’5’Dmt
D-Orn 3’5’Dmt Arg NH2
Mmt
D-Arg Phe Lys NH2
Mmt
D-Arg Phe Orn NH2
Mmt
D-Arg Phe Dab NH2
Mmt
D-Arg Phe Dap NH2
Tmt
D-Arg Phe Lys NH2
Tmt
D-Arg Phe Orn NH2
Tmt
D-Arg Phe Dab NH2
Tmt
D-Arg Phe Dap NH2
Hmt
D-Arg Phe Lys NH2
Hmt
D-Arg Phe Orn NH2
Hmt
D-Arg Phe Dab NH2
Hmt
D-Arg Phe Dap NH2
Mmt
D-Lys Phe Lys NH2
Mmt
D-Lys Phe Orn NH2
Mmt
D-Lys Phe Dab NH2
Mmt
D-Lys Phe Dap NH2
Mmt
D-Lys Phe Arg NH2
Tmt
D-Lys Phe Lys NH2
Tmt
D-Lys Phe Orn NH2
Tmt
D-Lys Phe Dab NH2
Tmt
D-Lys Phe Dap NH2
Tmt
D-Lys Phe Arg NH2
Hmt
D-Lys Phe Lys NH2
Hmt
D-Lys Phe Orn NH2
19
E10812524
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Hmt
D-Lys Phe Dab NH2
Hmt
D-Lys Phe Dap NH2
Hmt
D-Lys Phe Arg NH2
Mmt
D-Lys Phe Arg NH2
Mmt
D-Orn Phe Arg NH2
Mmt
D-Dab Phe Arg NH2
Mmt
D-Dap Phe Arg NH2
Mmt
D-Arg Phe Arg NH2
Tmt
D-Lys Phe Arg NH2
Tmt
D-Orn Phe Arg NH2
Tmt
D-Dab Phe Arg NH2
Tmt
D-Dap Phe Arg NH2
Tmt
D-Arg Phe Arg NH2
Hmt
D-Lys Phe Arg NH2
Hmt
D-Orn Phe Arg NH2
Hmt
D-Dab Phe Arg NH2
Hmt
D-Dap Phe Arg NH2
Hmt
D-Arg Phe Arg NH2
Dab = diaminobutírico Dap = ácido diaminopropiónico Dmt = dimetiltirosina Mmt = 2’-metiltirosina Tmt = N, 2’,6’-trimetiltirosina Hmt = 2’-hidroxi,6’-metiltirosina dnsDap = ácido β-dansil-L-α, β -diaminopropiónico atnDap = ácido β-antraniloil-L-α, β-diaminopropiónico Bio = biotina
Ejemplos de otros péptidos catiónicos aromáticos que no activan los receptores mu-opioides incluyen, pero no se limitan a, los péptidos catiónicos aromáticos mostrados en la Tabla 6.
20
E10812524
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TABLA 6. Análogos de péptidos Carentes de Actividad Mu-Opioide
Posición del Aminoácido 1
Posición del Aminoácido 2 Posición del Aminoácido 3 Posición del Aminoácido 4 Modificación del Terminal C
D-Arg
Dmt Lys Phe NH2
D-Arg
Dmt Phe Lys NH2
D-Arg
Phe Lys Dmt NH2
D-Arg
Phe Dmt Lys NH2
D-Arg
Lys Dmt Phe NH2
D-Arg
Lys Phe Dmt NH2
Phe
Lys Dmt D-Arg NH2
Phe
Lys D-Arg Dmt NH2
Phe
D-Arg Phe Lys NH2
Phe
D-Arg Dmt Lys NH2
Phe
D-Arg Lys Dmt NH2
Phe
Dmt D-Arg Lys NH2
Phe
Dmt Lys D-Arg NH2
Lys
Phe D-Arg Dmt NH2
Lys
Phe Dmt D-Arg NH2
Lys
Dmt D-Arg Phe NH2
Lys
Dmt Phe D-Arg NH2
Lys
D-Arg Phe Dmt NH2
Lys
D-Arg Dmt Phe NH2
D-Arg
Dmt D-Arg Phe NH2
D-Arg
Dmt D-Arg Dmt NH2
D-Arg
Dmt D-Arg Tyr NH2
D-Arg
Dmt D-Arg Trp NH2
Trp
D-Arg Phe Lys NH2
Trp
D-Arg Tyr Lys NH2
Trp
D-Arg Trp Lys NH2
Trp
D-Arg Dmt Lys NH2
21
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E10812524
30-07-2014
TABLA 8. Horario Terapéutico -Modelo HFD/STZ
Duración
Objetivo Grupos Diabéticos (A,B,C,D,E,F) Grupo Control (G)
1ª Semana
Aclimatación Alimentación Normal de Rata
2ª -7ª Semana
Manipulación de la Dieta Dieta Alta en Grasa Alimentación Normal de Rata
Final de 7ª Semana
Inyección STZ STZ 30 mg/kg, i.p., una vez Solución reguladora de citrato
8ª -27 Semana
Inducción de Diabetes Dieta alta en grasa hasta la semana 21, luego se cambia a alimentación normal de rata Alimentación Normal de Rata
Semana 28 -37
Tratamiento Peptídico Tratamiento Peptídico (ver Tabla 7) Grupo G: 2 mL/kg, s.c.
Semana 38
Muestras de sangre y orina recolectadas a las 24h, y órganos vitales recolectados
TABLA 9. Grupos de Tratamiento -Modelo STZ
Grupo
Número de Ratas Modelo Tratamiento Dosificación y Ruta
A
11 Diabetes SS-31 10 mg/kg s.c
B
11 Diabetes SS-20 10 mg/kg s.c.
C
10 Diabetes Solución salina Vol. igual s.c.
D
10 Normal Solución salina Vol. igual s.c.

TABLA 10. Horario Terapéutico -Modelo STZ
Duración
Objetivo Grupos Diabéticos (A,B,C) Grupo Control (D)
1ª y 3ª Semana
Aclimatación Alimentación Normal de Rata
Final de 3ª Semana
Inyección STZ STZ 30 mg/kg, i.p., una vez Solución reguladora de citrato
4ª -18ª Semana
Inducción de Complicaciones Diabéticas Alimentación Normal de Rata
Semana 19 -19
Tratamiento Peptídico Tratamiento Peptídico (ver Tabla 9) Grupo D: 2 mL/kg, s.c.
Semana 29
Muestras de sangre y orina recolectadas a las 24h, y órganos vitales recolectados
33
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Claims (1)

  1. imagen1
ES10812524.6T 2009-08-24 2010-08-23 Métodos y composiciones para prevenir o tratar condiciones oftálmicas Active ES2487633T3 (es)

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US23644009P 2009-08-24 2009-08-24
US236440P 2009-08-24
US23774509P 2009-08-28 2009-08-28
US237745P 2009-08-28
US34847010P 2010-05-26 2010-05-26
US348470P 2010-05-26
PCT/US2010/046338 WO2011025734A1 (en) 2009-08-24 2010-08-23 Methods and compositions for preventing or treating ophthalmic conditions

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ES2487633T3 true ES2487633T3 (es) 2014-08-22

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Family Applications (3)

Application Number Title Priority Date Filing Date
ES20156769T Active ES2964555T3 (es) 2009-08-24 2010-08-23 Péptido para uso en la prevención o tratamiento de la degeneración macular
ES23194389T Active ES3036317T3 (en) 2009-08-24 2010-08-23 Peptide for use in preventing or treating macular degeneration
ES10812524.6T Active ES2487633T3 (es) 2009-08-24 2010-08-23 Métodos y composiciones para prevenir o tratar condiciones oftálmicas

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ES20156769T Active ES2964555T3 (es) 2009-08-24 2010-08-23 Péptido para uso en la prevención o tratamiento de la degeneración macular
ES23194389T Active ES3036317T3 (en) 2009-08-24 2010-08-23 Peptide for use in preventing or treating macular degeneration

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US (8) US8470784B2 (es)
EP (18) EP2962695A1 (es)
JP (8) JP6120399B2 (es)
CN (3) CN102625709A (es)
CA (1) CA2772094C (es)
DK (2) DK2470191T3 (es)
ES (3) ES2964555T3 (es)
FI (1) FI3708178T3 (es)
HK (4) HK1204958A1 (es)
HR (1) HRP20231277T1 (es)
HU (1) HUE064800T2 (es)
LT (1) LT3708178T (es)
PL (2) PL3708178T3 (es)
PT (2) PT3708178T (es)
SI (2) SI3708178T1 (es)
SM (1) SMT202300433T1 (es)
WO (1) WO2011025734A1 (es)

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