WO1998003176A1 - Traitement de peritonite infectieuse feline a l'aide d'un agent anti-viral - Google Patents

Traitement de peritonite infectieuse feline a l'aide d'un agent anti-viral Download PDF

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Publication number
WO1998003176A1
WO1998003176A1 PCT/EP1997/003882 EP9703882W WO9803176A1 WO 1998003176 A1 WO1998003176 A1 WO 1998003176A1 EP 9703882 W EP9703882 W EP 9703882W WO 9803176 A1 WO9803176 A1 WO 9803176A1
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WO
WIPO (PCT)
Prior art keywords
treatment
compound
formula
pharmaceutically acceptable
fip
Prior art date
Application number
PCT/EP1997/003882
Other languages
English (en)
Inventor
Uschi Postl
Original Assignee
Smithkline Beecham Plc
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 Plc filed Critical Smithkline Beecham Plc
Priority to AU37687/97A priority Critical patent/AU3768797A/en
Publication of WO1998003176A1 publication Critical patent/WO1998003176A1/fr

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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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52—Purines, e.g. adenine
    • A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
    • 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
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/21—Interferons [IFN]

Definitions

  • This invention relates to treatment of medical conditions associated with infection with feline infectious peritonitis (FIP), and to the use of compounds in the preparation of a medicament for use in the treatment of such conditions.
  • FIP feline infectious peritonitis
  • 'treatment' includes prophylaxis as appropriate.
  • EP-A- 141927 (Beecham Group p.l.c.) discloses penciclovir, the compound of formula (A):
  • penciclovir and salts, phosphate esters and acyl derivatives thereof, as antiviral agents.
  • the sodium salt hydrate of penciclovir is disclosed in EP-A-216459 (Beecham Group p.l.c). Penciclovir and its antiviral activity is also disclosed in Abstract P.V11-5 p.193 of 'Abstracts of Nth Int. Congress of Microbiology', Manchester, England 7-13
  • the compounds of formulae (A) and (B) and salts and de ⁇ vatives thereof have been desc ⁇ bed as potentially effective in the treatment of infections caused by herpesviruses, such as herpes simplex type 1 , herpes simplex type 2, vancella-zoster, Epstein-Barr viruses, and cytomegalovirus Famciclovir, sold in the United Kingdom and the United States of America under the trademark, F ⁇ MVIR, is used for treating herpes zoster (shingles) and genital herpes.
  • Feline infectious pentonms (FIP) is a disease caused by a coronavirus infection. Many different strains of coronavirus are capable of infecting cats, but most do not produce senous disease.
  • FlP-producing strains are distinguished by their ability to invade and grow in certain white blood cells
  • the infected cells transpon the virus throughout the cat's body.
  • An intense inflammatory reaction occurs in the ussues where these virus-infected cells locate. It is this interaction between the body's own immune system and the virus that is responsible for the disease.
  • Infected cats shed coronavirus in their saliva and feaces Most cats become infected by inhaling or ingesting the virus, either by direct contact with an infected cat, or by contact with virus-contaminated surfaces like clothing, bedding, feeding bowls, or toys.
  • lethal FIP lethal FIP
  • effusive FIP effusive FIP
  • noneffusive FIP noneffusive FIP
  • combinations of both The most characteristic sign of effusive FIP is the accumulation of fluid within the abdomen and/or chest. When fluid accumulation becomes excessive, it may become difficult for the cat to breathe normally.
  • FIP Fluorouracil
  • the basic aim of therapy is to provide supportive care and to alleviate the self-destroying inflammatory response of the disease.
  • Some ⁇ eatments may induce short-term remissions in a small percentage of patients.
  • a combination of corticosteroids, cytotoxic drugs, and antibiotics with maintenance of nutrient and fluid intake may be helpful in some cases
  • the present invention provides a method of treatment of FIP infection in humans, which method compnses the administration to the human in need of such treatment, an effective amount of a compound of formula (A):
  • acyl denva ⁇ ve' is used herein to include any de ⁇ vative of the compounds of formula (A) in which one or more acyl groups are present. Such derivauves are included as bioprecursors of the compounds of formula (A) in addition to those derivatives which are per se biologically active
  • the compound of formula (A) may be in one of the forms disclosed in EP-A-216459 (Beecham Group p.l.c).
  • a particular compound of formula (B) of interest ts 9-(4-acetoxy-3-acetoxymethylbut- l-yl)-2-am ⁇ nopunne, known as famciclovir (FCV), the well-absorbed oral form of penciclovir (PCV).
  • FCV famciclovir
  • PCV penciclovir
  • the compound of formula (A), bioprecursors, salts and de ⁇ vatives may be prepared as described in the aforementioned European Patent references.
  • the compound, in pa ⁇ icular, famciclovir may be administered by the oral route to humans and may be compounded in the form of syrup, tablets or capsule.
  • any pharmaceutical earner 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 flavou ⁇ ng or colou ⁇ ng agents may be added to form syrups.
  • 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 stenle vehicle.
  • a surfactant or wetting agent is included in the composition to facilitate uniform distribution of the compound of the invention.
  • Preferred parenteral formulations include aqueous formulations using sterile water or normal saline, at a pH of around 7.4 or greater, in particular, containing penciclovir sodium salt hydrate.
  • 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 seventy of the infection and the weight of the mammal.
  • a suitable dosage unit might contain from 50mg to 5g of active ingredient, such as lOOmg to 2g, for example 100 to 500 or 1500mg. 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 or, more usually, 10 to 20 mg/kg per day.
  • the dosage unit may be 25mg, 30mg, 40mg, 50mg, 60mg, 70mg, 75mg, 80mg, lOOmg, 125mg, 250 mg, 500 mg.
  • the present invention also provides the use of a compound of formula (A) or a bioprecursor. or a pharmaceutically acceptable salt, phosphate ester and/or acyl derivative of either of the foregoing, in the preparation of a medicament for use in the treatment of FIP 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 FIP infection, which comprises an effective amount of a compound of formula (A) or a bioprecursor, or a pharmaceutically acceptable salt, phosphate ester and/or acyl derivative of either of the foregoing, and a pharmaceutically acceptable carrier.
  • a pharmaceutical composition for use in the treatment of FIP infection which comprises an effective amount of a compound of formula (A) or a bioprecursor, or a pharmaceutically acceptable salt, phosphate ester and/or acyl derivative of either of the foregoing, and a pharmaceutically acceptable carrier.
  • Such compositions may be prepared in the manner as hereinafter described.
  • the compound of formula (A) and its prodrugs show a synergistic antiviral effect in conjunction with interferons; and treatment using combination products comprising these two components for sequential or concomitant administration, by the same or different routes, are therefore within the ambit of the present invention.
  • Such products are described in EP-A-271270 (Beecham Group p.l.c).
  • Combinations with other immunomodulatory compounds, such as other cytokines or cytokine inducers, or other compounds that stimulate or suppress the immune response are also within the ambit of this invention.
  • the cat 'Paula' aged 18.5 months was diagnosed with FIP and showed symptoms of effusive FIP, has been treated with 1/4 of a 250mg tablet of famciclovir twice a day without interruption. After one day of treatment the condition improved and this improvement was maintained. After 3 months of treatment, tests for small amount of coronavirus antibodies in the serum showed that the titre value i.e. the highest serum dilution that still produced a positive reaction small amount of coronavirus antibodies in the serum, had decreased from 1 :300 to 1 : 1600. After 8 months of treatment the cat is still in good condition.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Zoology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Cette invention concerne l'utilisation d'un composé correspondant à la formule (A) ou d'un bio-précurseur de celui-ci ou, encore, d'un sel, d'un ester de phosphate et/ou d'un dérivé acyle de l'un ces derniers qui soit acceptable sur le plan pharmaceutique. Ces éléments sont utilisés dans la fabrication d'un médicament permettant de traiter et de prévenir des infections de type péritonite infectieuse féline (PIF).
PCT/EP1997/003882 1996-07-18 1997-07-16 Traitement de peritonite infectieuse feline a l'aide d'un agent anti-viral WO1998003176A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU37687/97A AU3768797A (en) 1996-07-18 1997-07-16 Treatment of feline infections peritonitis by an antiviral

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9615111.3 1996-07-18
GBGB9615111.3A GB9615111D0 (en) 1996-07-18 1996-07-18 Pharmaceuticals

Publications (1)

Publication Number Publication Date
WO1998003176A1 true WO1998003176A1 (fr) 1998-01-29

Family

ID=10797131

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1997/003882 WO1998003176A1 (fr) 1996-07-18 1997-07-16 Traitement de peritonite infectieuse feline a l'aide d'un agent anti-viral

Country Status (3)

Country Link
AU (1) AU3768797A (fr)
GB (1) GB9615111D0 (fr)
WO (1) WO1998003176A1 (fr)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0271270A2 (fr) * 1986-12-02 1988-06-15 Beecham Group Plc Produits pharmaceutiques

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0271270A2 (fr) * 1986-12-02 1988-06-15 Beecham Group Plc Produits pharmaceutiques

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
ASHTON ET AL.: "Antiviral activity of famciclovir and acyclovir in mice infected intraperitoneally with herpes simplex virus type 1 SC16", J. ANTIMICROB. CHEMOTHER., vol. 34, 1994, pages 287 - 290, XP002044863 *
GOLDTHORPE ET AL.: "Effects of penciclovir and famciclovir in a murine model of encephalitis induced by intranasal inoculation of herpes simplex virus type 1.", ANTIVIRAL CHEM. CHEMOTHER., vol. 3, no. 1, 1992, pages 37 - 47, XP002044811 *
MACY, D. W.: "Use of Antiviral Agents in Cats", FELINE PRACTICE, vol. 23, no. 5, 1995, pages 25 - 26, XP002046518 *
SUTTON ET AL.: "Activity of famciclovir and penciclovir in HSV-infected animals: a review.", ANTIVIRAL CHEM. CHEMOTHER., vol. 4, no. 1, 1993, pages 37 - 46, XP002044809 *
SUTTON ET AL.: "Comparative Activity of Penciclovir and Acyclovir in Mice Infected Intraperitoneally with Herpes Simplex Virus Type SC16", ANTIMICROB. AGENTS CHEMOTHER., vol. 37, no. 4, 1993, pages 642 - 645, XP002044810 *

Also Published As

Publication number Publication date
AU3768797A (en) 1998-02-10
GB9615111D0 (en) 1996-09-04

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