EP1420808A1 - Traitement de la tuberculose au moyen de composes immunomodulateurs - Google Patents

Traitement de la tuberculose au moyen de composes immunomodulateurs

Info

Publication number
EP1420808A1
EP1420808A1 EP01271057A EP01271057A EP1420808A1 EP 1420808 A1 EP1420808 A1 EP 1420808A1 EP 01271057 A EP01271057 A EP 01271057A EP 01271057 A EP01271057 A EP 01271057A EP 1420808 A1 EP1420808 A1 EP 1420808A1
Authority
EP
European Patent Office
Prior art keywords
tryptophan
scv
tuberculosis
group
therapy
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
EP01271057A
Other languages
German (de)
English (en)
Other versions
EP1420808A4 (fr
Inventor
Alexander A. Kolobov
Andrey S. Simbirtsev
Tat'yana I. Vinogradova
Natal'ya V. Zabolotnyh
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sciclone Pharmaceuticals LLC
Original Assignee
Sciclone Pharmaceuticals LLC
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 Sciclone Pharmaceuticals LLC filed Critical Sciclone Pharmaceuticals LLC
Priority to EP09000806A priority Critical patent/EP2078525A3/fr
Publication of EP1420808A1 publication Critical patent/EP1420808A1/fr
Publication of EP1420808A4 publication Critical patent/EP1420808A4/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • 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
    • A61K38/05—Dipeptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A61P31/06—Antibacterial agents for tuberculosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators

Definitions

  • the present invention relates generally to a method for treating tuberculosis in
  • mammals including mammals such as humans.
  • Tuberculosis is a chronic, infectious disease that is caused by infection with tubercle
  • Tuberculosis strikes people of all ages but is more common among the
  • the disease can afflict animals, including
  • Mycobacterium tuberculosis is the
  • Known therapies in the art include isoniazid (isonicotinic acid hydrazide), rifampicin
  • pyrazinamide PZA
  • kanamycin ethambutol
  • streptomycin ethambutol
  • capreomicin amicacin
  • Isomazid is still a front-line therapy against tuberculosis and modem short-
  • tuberculosis can generally be controlled using extended antibiotic therapy, this treatment is
  • mammal e.g., human
  • n 1 or 2
  • R is hydrogen, acyl, alkyl or a peptide fragment
  • X is an
  • Spleen cell proliferation data is presented. Restoration of the mitogen (Con A and LPS) induced response in SCV-07 treated animals occurs sooner than the isoniazid treated animals.
  • proliferative response with LPS in Group 6 (1 ig/kg, 10 injections ip) and with Con A in Groups 6 and 7 (1 ig/kg, 10 injections ip and 0.1 ig/kg ip) did not differ from uninfected mice. Meanwhile, in Group 3 the isoniazid control group, the proliferative response remained low.
  • Spleen cells and thymic cells were isolated as described above.
  • thymic cells were diluted to 10 7 /ml in RPMI-1640 with 2mM L-glutamine, 80 ig/ml gentamycin and 4% heat-inactivated fetal calf serum (Sigma, St. Louis, MO).
  • Spleen cells were diluted to 3 x 10 6 /ml in RPMI-1640 with 2mM L-glutamine, 80 ig/ml gentamycin and 20% inactivated fetal calf serum.
  • 0.5 ig/ml Concanavalin A Con A, Sigma, St. Louis, MO was used to stimulate thymic cell proliferation.
  • SCV-07 treatment particularly in Groups 6 and 7 (1.0 ig/kg, 10 injections and 0.1 ig/kg ip), significantly improved macrophage killing.
  • Peritoneal cell suspensions in Eagle media were centrifuged at 1200 rpm. The media was decanted, cells were washed in 0.9% saline solution and resuspended in 0.1% NBT HBSS solution at pH 7.2. These reactions occurred in 96-well plates. The counted cells were placed in the wells in a volume of 100 il and incubated at 37 °C in humidified CO 2 for 1 h. After incubation, the supernatant was decanted, plates were dried at room temperature and cells were fixed in 70% methanol. In a solution of 2 M potassium hydroxide and 140 il DMSO, diformazane was added. Using a plate reader, plates were read at 640 nm and results were expressed as the extinction coefficient (related to cell number in the sample).
  • spleen cells were diluted to a concentration of 10 7 /ml with 10% fetal calf serum, 2mM L-glutamine and 80 ig/ml gentamycin.
  • a 100 il cell suspension was added to each well of a 96-well culture plate and cytokine production was induced by Con A at a final concentration of 2.5ig/ml.
  • a control well included RPMI-1640.
  • cells were incubated at 37 ° C and humidified in 5% CO 2 . Following incubation, 150 il of supernatant was removed from each well and stored at -70° C.
  • IL-4 and INF- ⁇ assays in Con A-stimulated spleen cell supernatants were also performed using Quantikine TM ELIZA kits R & D Systems, Minneapolis, MN) in accordance with kit instructions. Plates were coated with monoclonal antibodies to either IL-4 or IFN- ⁇ and blocked. Standards and samples were subsequently added. The cells were incubated for 2 h and washed, following with the addition of a colorimetric substrate. After 30 minutes, the reaction was terminated and plates were read at 450 nm using a plate reader (Multiscan TM 3550, BioRad, Japan).
  • INF- ⁇ and IL-4 concentrations in blood serum After 10 days of SCV-07 therapy, IFN- ⁇ levels increased in Groups 4, 5, 6 and 7 (10 and 1 ig/kg ip, 5 injections; 1 ig/kg ip, 10 injections; and 0.1 ig/kg ip) while IL-4 levels decreased in the same groups. These changes also similarly occurred after 17 days of SCV-07 therapy.
  • SCV-07 treatment during isoniazid tuberculosis therapy influences the severity of the disease and the strength of the immune response.
  • SCV-07 provided in 5 daily ip injections at a dose of 0.1 ig/kg significantly decreases both the lung weight index and the lung damage index.
  • M. bovis growth in spleen culture also decreases in these mice as well as mice treated with 10 daily injections at a dose of 1.0 ig/kg and mice treated with 5 daily injections of 0.01 ig/kg.
  • SCV-07 stimulation of macrophage function occurs, but an improvement of ingesting and killing ability which had been decreased by tuberculosis infection and isoniazid therapy occurs.
  • Production of cytokines increases with the treatment of SCV-07.
  • Production of IL-2 by spleen cells decreases from infection with tuberculosis; however, a significantly less reduction 4 days after SCV-07 treatment occurs in certain groups. After 24 days of treatment, production of IL-2 in other groups is restored to the uninfected animal level.

Abstract

On traite la tuberculose, chez des animaux, en administrant une quantité thérapeutiquement efficace d'un immunomodulateur représenté par la formule (A). Dans cette formule, n est 1 ou 2, R est hydrogène, acyle, alkyle ou un fragment de peptide et X est un amino acide aromatique ou hétérocyclique ou un dérivé de celui-ci. L'animal peut être un mammifère, et ce traitement peut aussi être administré à l'homme.
EP01271057A 2001-06-08 2001-12-20 Traitement de la tuberculose au moyen de composes immunomodulateurs Withdrawn EP1420808A4 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP09000806A EP2078525A3 (fr) 2001-06-08 2001-12-20 Traitement de la tuberculose au moyen de composés immunomodulateurs

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
RU2001115900/14A RU2229892C2 (ru) 2001-06-08 2001-06-08 Способ лечения туберкулеза легких
RU2001115900 2001-08-06
PCT/US2001/048560 WO2003013572A1 (fr) 2001-06-08 2001-12-20 Traitement de la tuberculose au moyen de composes immunomodulateurs

Related Child Applications (1)

Application Number Title Priority Date Filing Date
EP09000806A Division EP2078525A3 (fr) 2001-06-08 2001-12-20 Traitement de la tuberculose au moyen de composés immunomodulateurs

Publications (2)

Publication Number Publication Date
EP1420808A1 true EP1420808A1 (fr) 2004-05-26
EP1420808A4 EP1420808A4 (fr) 2006-06-07

Family

ID=20250617

Family Applications (2)

Application Number Title Priority Date Filing Date
EP09000806A Withdrawn EP2078525A3 (fr) 2001-06-08 2001-12-20 Traitement de la tuberculose au moyen de composés immunomodulateurs
EP01271057A Withdrawn EP1420808A4 (fr) 2001-06-08 2001-12-20 Traitement de la tuberculose au moyen de composes immunomodulateurs

Family Applications Before (1)

Application Number Title Priority Date Filing Date
EP09000806A Withdrawn EP2078525A3 (fr) 2001-06-08 2001-12-20 Traitement de la tuberculose au moyen de composés immunomodulateurs

Country Status (4)

Country Link
EP (2) EP2078525A3 (fr)
JP (1) JP4837251B2 (fr)
RU (1) RU2229892C2 (fr)
WO (1) WO2003013572A1 (fr)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20070012522A (ko) * 2004-05-14 2007-01-25 사이클론 파아머슈티컬 인코오퍼레이티드 면역조절제 화합물로의 호흡기 바이러스 감염의 치료 및예방
WO2006116053A1 (fr) * 2005-04-22 2006-11-02 Sciclone Pharmaceuticals, Inc. Composes immunomodulateurs favorisant l'efficacite vaccinale
CN101657210A (zh) 2007-02-13 2010-02-24 希克龙制药公司 粘膜疾病引起的组织退化、损伤或损害的治疗或预防方法
BRPI0815772A2 (pt) * 2007-08-23 2014-09-30 Sciclone Pharmaceuticals Inc Tratamento de câncer de pulmão
RU2450820C2 (ru) * 2010-07-20 2012-05-20 Государственное учреждение "Научно-практический центр "Фтизиатрия" Министерства здравоохранения республики Саха (Якутия) Способ лечения деструктивного туберкулеза легких

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994020063A2 (fr) * 1993-03-04 1994-09-15 Cytoven International N.V. Tryptophane pharmaceutique contenant des compositions dipeptidiques et modes d'utilisation
WO1997019691A1 (fr) * 1995-11-28 1997-06-05 Wei, Edward, T. Composes immunomodulateurs contenant du gamma-l-glutamyl et procedes afferents
US5916878A (en) * 1995-11-28 1999-06-29 Edward T. Wei γ-glutamyl and β-aspartyl containing immunomodulator compounds and methods therewith
US6060452A (en) * 1996-03-13 2000-05-09 Cytran, Inc. Analogs of L-Glu-L-Trp having pharmacological activity

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4520196A (en) * 1983-08-18 1985-05-28 American Home Products Corporation α-Mercaptophenylacetic acid derivatives of imidazole-containing compounds and analogues thereof
US5212192A (en) * 1989-11-24 1993-05-18 Janssen Pharmaceutica N.V. Immunostimulating 6-aryl-5,6-dihydroimidazo[2,1-b]thiazole derivatives
WO1997021444A1 (fr) * 1995-12-14 1997-06-19 Mark Borisovich Balazovsky Activateur de production endogene de facteur hemopoietique et de cytokine, et procedes d'utilisation

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994020063A2 (fr) * 1993-03-04 1994-09-15 Cytoven International N.V. Tryptophane pharmaceutique contenant des compositions dipeptidiques et modes d'utilisation
WO1997019691A1 (fr) * 1995-11-28 1997-06-05 Wei, Edward, T. Composes immunomodulateurs contenant du gamma-l-glutamyl et procedes afferents
US5916878A (en) * 1995-11-28 1999-06-29 Edward T. Wei γ-glutamyl and β-aspartyl containing immunomodulator compounds and methods therewith
US6060452A (en) * 1996-03-13 2000-05-09 Cytran, Inc. Analogs of L-Glu-L-Trp having pharmacological activity

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US 1990 Database accession no. PREV199090100455 & BUCHAN G.S. ET AL: 'Tuberculosis in domesticated deer cervus-elaphus a large anumal model for tuberculosis' JOURNAL OF COMPARATIVE PATHOLOGY vol. 103, no. 1, 1990, pages 11 - 22 *
DATABASE CIN [Online] "Other Research News" XP002377620 retrieved from STN Database accession no. 29(11):11078F & BIOCENTURY, 8(10, PT. 2), P. B13. ISSN: 1097-7201; CODEN: BICEFS., 28 February 2000 (2000-02-28), *
DATABASE IMSDRUGNEWS [Online] R & D Focus Drug News; 22 January 2001 (2001-01-22), XP002377621 retrieved from STN Database accession no. AN = 2001:333 *
DATABASE IMSDRUGNEWS [Online] R & D Focus Drug News; 6 September 1999 (1999-09-06), XP002377619 retrieved from STN Database accession no. 1999:2565 *
NICOLAUS B.J.R.: 'symbiotic approach to drug design' DECISION MAKING IN DRUG RESEARCH 1983, pages 173 - 186, XP002197412 *
See also references of WO03013572A1 *

Also Published As

Publication number Publication date
EP1420808A4 (fr) 2006-06-07
RU2229892C2 (ru) 2004-06-10
EP2078525A3 (fr) 2010-09-08
EP2078525A2 (fr) 2009-07-15
WO2003013572A1 (fr) 2003-02-20
JP2004537579A (ja) 2004-12-16
JP4837251B2 (ja) 2011-12-14

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