Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Phosphorus containing other than solely as part of an...
Patent
1996-03-08
2000-09-12
Krass, Frederick
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Phosphorus containing other than solely as part of an...
514261, 514262, 424450, A61K 3152, A61K 3166, A61K 3170, A61K 4726
Patent
active
061178578
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to a pharmaceutical composition comprising an antiviral compound selected from the group consisting of foscarnet, acyclovir, valaciclovir, penciclovir and famciclovir, which is suitable for topical, but also for parenteral administration. The composition can be used in the prophylactic and curative treatment of infections caused by herpesviruses and other viruses on which said antiviral compound has an effect.
BACKGROUND OF THE INVENTION
Herpesvirus infections in humans can be induced by six known human herpesviruses, the most common being herpes simplex virus and varicella-zoster virus. There are also many animal herpesviruses.
Herpes simplex viruses can be divided into two serotypes, type 1 (HSV-1) and type 2 (HSV-2), the clinical manifestations of which range from benign self-limiting oral-facial and genital infections to potentially life threatening conditions like encephalitis and generalized neonatal infections.
Oral-facial HSV infections are primarily caused by HSV-1. Following a primary infection in childhood the virus becomes latent in the sensory nerve cells, most often the trigeminal ganglion, for the rest of the invididual's life. The virus can subsequently be reactivated at different times. Following a reactivation in the nerve cell, the virus is transported through the nerves to the skin and subsequently develops a recurrent oral-facial HSV infection more commonly known as a cold sore. About half of the patients experience prodromal symptoms such as pain, burning or itching at the site of the subsequent eruption. The condition is generally rapidly self-limiting and a typical episode will heal in around 10 days from the first symptoms. Viral replication in the lip is initiated early and maximal virus load is obtained 24 hours following onset of the recurrence. The virus concentration is then dramatically reduced and virus can not be isolated 70-80 hours after onset in the typical patient.
The clinical presentation of genital HSV infections is similar to the oral-facial infections with a couple of important exceptions. Genital HSV infections are most often caused by HSV-2 and following a primary infection the virus will latently infect sensory or autonomic ganglions. Reactivation will produce the local recurrent lesions that are characteristic of the herpes infection on or near the genitals.
Varicella-zoster virus (VZV) is also a member of the herpesvirus group. The primary infection is known to cause chickenpox. Like HSV, VZV becomes latent following the primary infection and can like HSV be reactivated as herpes zoster later on in life. Zoster usually results in skin rash and intensive acute pain. In 30% of the patients, the pain can be prolonged and continue for weeks or months after the rash has cleared up.
Cytomegalovirus (CMV), Epstein-Barr virus (EBV) and human herpesvirus 6 (HHV-6 ) are the other known human herpesviruses.
Primary CMV infection in the normal host is usually not accompanied by symptoms, but occasionally symptoms of CMV mononucleosis may appear. In the blood, CMV resides mainly in the polymorphonuclear leucocytes, but monocytes and occasionally T lymphocytes may harbor CMV in a form as yet unidentified.
Most human EBV infections start in the oropharyngeal epithelium. Early in the course of primary infection EBV infects B lymphocytes. EBV does not usually replicate productively in B lymphocytes but instead establishes latent infection.
HIV is a retrovirus which infects and destroys lymphocytes bearing the CD4 cell marker, causing progressive immunodeficiency. Foscarnet inhibits the reverse transcriptase of HIV and shows antiviral activity against the replication of HIV in vitro.
There are a number of antiviral agents which are active against the human herpesviruses. However, so far there has only been limited clinical success in the treatment of recurrent herpesvirus infections in immunocompetent patients.
Foscarnet, the hexahydrate of the trisodium salt of phosphonoformic acid (sodium phosphonoformate hexahydrate),
REFERENCES:
Palmer, S. et al.: Intracellular Activiation and Cytotoxicity of Three Different Combinations of 3'-Azido-3'-deoxythymidine and 2', 3'-Dideoxythymidine, AIDS Research and Human Retroviruses, vol. 11, No. 10, 1995.
Foley: Permeability of liposomes composed of binary mixtures of MGDG and DGDG, Biochem et Biophys Acta 939 (1988).
Biosynthesis and function of plant lipids, et. Tomson et al., 1983, Sprague, S. et al.: Bilayer and non-bilayer configurations of mixtures of isolated chloroplast membrane lipids.
Jocham, U.E.: LOAD--Liposomen topisch appliziert, Pharmaceutische Zeitung Nr 33, Aug. 13, 1992.
Schreier, H.: Liposomes and niosomes as topical drug carriers: dermal and transdermal drug delivery, Journal of Controlled Release 30 (1994), 1-15.
Bakker-Woudenberg, I.A.J.M. et al.: Increased Efficacy of Ganciclovir and Foscarnet Inhibition of Cytomegalovirus Replication in Vitro by Encapsulation in Liposomes, Scand J Infect Dis. Suppl. 74: 54-57, 1991.
Spruance, S.L.: Topical therapy of Mucotaneous Herpesvirus Infections, International Antiviral News, Jun. 1994.
Abele, G. et al.: Antiviral activity against VZV and HSV type 1 and type 2 of the (+) and (-) enantiomers of (r,S)-9-[4-hydroxymethyl)butyl]guanine, in comparison to other closely related acyclic nucleosides, Antiviral Chemistry and Chemotherapy (1991) 2(3), 163-169.
Merk Index 10th ed #4135, 1984.
Bakker-Woudenberg et al, Scand J. Infect. Dis, Suppl 74 pp. 54-57, 1991.
Carlsson Anders Nils-Erik
Herslof Bengt Goran
Lundquist Stefan Karl
Nilsson Goran Nils Gunnar
Astra Aktiebolag
Krass Frederick
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