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WO1996014847A1 - Utilisation d'acides phosphonoacetiques ou phosphonoformiques contre le virus de l'herpes -7 humain (hhv-7) - Google Patents

Utilisation d'acides phosphonoacetiques ou phosphonoformiques contre le virus de l'herpes -7 humain (hhv-7) Download PDF

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Publication number
WO1996014847A1
WO1996014847A1 PCT/EP1995/004445 EP9504445W WO9614847A1 WO 1996014847 A1 WO1996014847 A1 WO 1996014847A1 EP 9504445 W EP9504445 W EP 9504445W WO 9614847 A1 WO9614847 A1 WO 9614847A1
Authority
WO
WIPO (PCT)
Prior art keywords
hhv
treatment
infection
phosphonoacetic
activity against
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.)
Ceased
Application number
PCT/EP1995/004445
Other languages
English (en)
Inventor
Raymond F. Schinazi
Paul M. Feorino
Richard Anthony Vere Hodge
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.)
SmithKline Beecham Ltd
Original Assignee
SmithKline Beecham Ltd
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 SmithKline Beecham Ltd filed Critical SmithKline Beecham Ltd
Priority to EP95937066A priority Critical patent/EP0790828A1/fr
Priority to JP8515727A priority patent/JPH10509704A/ja
Publication of WO1996014847A1 publication Critical patent/WO1996014847A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/662—Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
    • 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
    • A61P31/12—Antivirals
    • 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
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A61P31/22—Antivirals for DNA viruses for herpes viruses

Definitions

  • This invention relates to treatment of infection caused by human herpesvirus 7 (HHV-7), and to the use of compounds in the preparation of a medicament for use in the treatment of such conditions.
  • HHV-7 human herpesvirus 7
  • Phosphonoacetic Acid PAA
  • PFA phosphonoformic acid
  • PFA foscarnet
  • PHA Phosphonoacetic Acid
  • PFA phosphonoformic acid
  • HHV-7 Human herpesvirus 7 (HHV-7) is a recently discovered member of the family Herpesviridae. The virus was first isolated in 1989 from the peripheral blood lymphocytes (PBL) of a healthy individual that were being cultured under conditions that lead to T-cell activation.
  • PBL peripheral blood lymphocytes
  • HHV-7 has been isolated from the saliva of as many as 75% of healthy adults. Antibodies to HHV-7 can be detected in serum specimens from approximately 90% of the normal population and seroconversion usually occurs during childhood after the age of 2. It is possible that HHV-7 may play a role in the activation of human immunodeficiency virus (HIV-1).
  • the present invention provides a method of treatment of HHV-7 infection in humans, which method comprises the administration to the human in need of such treatment, an effective amount of a pyrophosphate analogue having activity against herpesviruses.
  • the compound may be administered in the form of a bioprecursor or pharmaceutically acceptable salt.
  • fluid unit dose forms are prepared containing the compound and a sterile vehicle.
  • the compound depending on the vehicle and the concentration, can be either suspended or dissolved.
  • Parenteral solutions are normally prepared by dissolving the compound in a vehicle and filter sterilising before filling into a suitable vial or ampoule and sealing.
  • adjuvants such as a local anaesthetic, preservatives and buffering agents are also dissolved in the vehicle.
  • the composition can be frozen after filling into the vial and the water removed under vacuum.
  • Parenteral suspensions are prepared in substantially the same manner except that the compound is suspended in the vehicle instead of being dissolved and sterilised by exposure to ethylene oxide before suspending in the sterile vehicle.
  • a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the compound of the invention.
  • the compound may be administered by the oral route to humans and may be compounded in the form of syrup, tablets or capsule.
  • any pharmaceutical carrier suitable for formulating such solid compositions may be used, for example magnesium stearate, starch, lactose, glucose, rice, flour and chalk.
  • the compound may also be in the form of an ingestible capsule, for example of gelatin, to contain the compound, or in the form of a syrup, a solution or a suspension.
  • Suitable liquid pharmaceutical carriers include ethyl alcohol, glycerine, saline and water to which flavouring or colouring agents may be added to form syrups.
  • compositions will usually be accompanied by written or printed directions for use in the medical treatment concerned.
  • An amount effective to treat the virus infection depends on the nature and severity of the infection and the weight of the mammal.
  • a suitable dosage unit might contain from 50mg to lg of active ingredient, for example 100 to 500mg. Such doses may be administered 1 to 4 times a day or more usually 2 or 3 times a day.
  • the effective dose of compound will, in general, be in the range of from 0.2 to 40mg per kilogram of body weight per day.
  • the usual dosage for foscarnet in treatment of cytomegalovirus infections are as indicated on the British product data sheet, beginning with a 30 minute infusion of 20 mg/kg body weight.
  • the present invention also provides the use of a pyrophosphate analogue having activity against herpesviruses in the preparation of a medicament for use in the treatment of HHV-7 infection. Such treatment may be carried out in the manner as hereinbefore described.
  • the present invention further provides a pharmaceutical composition for use in the treatment of HHV-7 infection, which comprises an effective amount of a pyrophosphate analogue having activity against herpesviruses, and a pharmaceutically acceptable carrier.
  • a pharmaceutical composition for use in the treatment of HHV-7 infection which comprises an effective amount of a pyrophosphate analogue having activity against herpesviruses, and a pharmaceutically acceptable carrier.
  • Such compositions may be prepared in the manner as hereinafter described.
  • Human mononuclear cells were isolated from umbilical cord blood and inoculated in triplicate with the test virus. One hour later, duplicate dilutions of the compound were added, resulting in 0, 5, 10, 50, or 100 ⁇ M final concentrations. After 3 - 6 days, cellls were removed and tested for the presence of virus by indirect immunofluorescence (IFA) using type specific monoclonal antibodies. Three fields of 100 cells each were read from each sample.
  • IFA indirect immunofluorescence
  • a Dilutions of the compounds were added 1 hr after viral inoculation of human cord blood.
  • the % infected cells was measured by anti-complement immunofluorescence (ACIF).
  • ACIF anti-complement immunofluorescence
  • AU numbers are averages of results of cord blood from 3 donors and triplicate readings were performed on each sample. Each reading represents actual counting of 3 fields.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Virology (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

On décrit l'utilisation d'un analogue du pyrophosphate, lequel possède une activité contre les virus de l'herpès, dans la fabrication d'un médicament utile dans le traitement (notamment la prophylaxie) de l'infection à HHV-7.
PCT/EP1995/004445 1994-11-11 1995-11-10 Utilisation d'acides phosphonoacetiques ou phosphonoformiques contre le virus de l'herpes -7 humain (hhv-7) Ceased WO1996014847A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP95937066A EP0790828A1 (fr) 1994-11-11 1995-11-10 Utilisation d'acides phosphonoacetiques ou phosphonoformiques contre le virus de l'herpes -7 humain (hhv-7)
JP8515727A JPH10509704A (ja) 1994-11-11 1995-11-10 ヒト・ヘルペスウイルス−７（ｈｈｖ−７）に対するホスホノ酢酸またはホスホノギ酸の使用

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9422781.6 1994-11-11
GB9422781A GB9422781D0 (en) 1994-11-11 1994-11-11 Pharmaceuticals

Publications (1)

Publication Number Publication Date
WO1996014847A1 true WO1996014847A1 (fr) 1996-05-23

Family

ID=10764242

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1995/004445 Ceased WO1996014847A1 (fr) 1994-11-11 1995-11-10 Utilisation d'acides phosphonoacetiques ou phosphonoformiques contre le virus de l'herpes -7 humain (hhv-7)

Country Status (4)

Country Link
EP (1) EP0790828A1 (fr)
JP (1) JPH10509704A (fr)
GB (1) GB9422781D0 (fr)
WO (1) WO1996014847A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2177788C2 (ru) * 1998-06-10 2002-01-10 Данилов Леонид Леонидович Средство для профилактики и лечения инфекционных заболеваний и коррекции патологических состояний живого организма
RU2542420C1 (ru) * 2014-03-13 2015-02-20 Общество С Ограниченной Ответственностью "Гамаветфарм" Лекарственное средство на основе полипренилфосфатов и бета-ситостерина и способ его получения

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
D.V. ABLASHI ET AL.: "Human herpesvirus-6 (HHV-6)", IN VIVO, vol. 5, no. 3, pages 193 - 199, XP000564259 *
P. SECCHIERO ET AL.: "Quantitative PCR for human herpesviruses 6 and 7", J. CLIN. MICROBIOL., vol. 33, no. 8, pages 2124 - 2130, XP000564243 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2177788C2 (ru) * 1998-06-10 2002-01-10 Данилов Леонид Леонидович Средство для профилактики и лечения инфекционных заболеваний и коррекции патологических состояний живого организма
RU2542420C1 (ru) * 2014-03-13 2015-02-20 Общество С Ограниченной Ответственностью "Гамаветфарм" Лекарственное средство на основе полипренилфосфатов и бета-ситостерина и способ его получения

Also Published As

Publication number Publication date
JPH10509704A (ja) 1998-09-22
EP0790828A1 (fr) 1997-08-27
GB9422781D0 (en) 1995-01-04

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