Medicinal composition for the treatment of certain neuroviruses

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...

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Details

514562, 514566, 514934, A61K 3119, A61K 31195

Patent

active

046893474

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE INVENTION

The present invention relates to a medicinal composition for the treatment of neuroviruses, specifically herpes Zoster and herpes (herpes Simplex).


BACKGROUND OF THE INVENTION

Certain pharmeceutical compositions are known to be effective against herpes Zoster; the antibiotic Rifamycin or the immune stimulating agent Isoprinosine (Lesourd B, Loude, J., Meunier, P., Doumerc, P., Moulias, R., Traitement du zona ZOSTER par Isoprinosine, La nouv. Presse Medicale, Jan. 23 1982, II, No. 3, p. 191) and other chemotherapeutic compounds such as idoxuridine (Juel Jensen B.E., Treatment of Zoster with Idoxuridine in Dimethylsulfoxide; Result of Two Blind Control Trials; Brit. Med. J. 1970 (4), pp 776-780; cytosine arabinoside (Pierle, l.N., Cytosine Arabinoside for Herpes Zoster, New Eng. J. Med., 1974,290, pp 404-410) and adenine arabinoside (Whitely, R.J. et al, Adenine Arabinoside Therapy for Herpes Zoster, New Eng. J. Med., 1976, 294, pp 1193-1199).
Isoprinoside has a slow curvature action upon Zoster eruption; its effect upon pain is practically insignificant. The other substances, idoxuridine, cytosine, arabinoside, and adenine arabinoside are contraindicated on account of side effects.
The antivirotic action of several classes of chelators has been ascertained as against a large spectrum of viruses (Perrin D.D. and Stunzi H., 1981 - Pharmac.Ther.22, 255) in in vitro studies or in animal studies; even certain compounds of the class of thiosemicarbazones were proved to be active in the prophylaxis of chicken pox in an epidemic in Madras. In our country. Gh.D.Grigorescu wrote (in 1955) that dimercapto-propanol (DMP; BAL) is effective against herpes Zoster and against some other viroses (1973); however, DMP is not indicated for human use to the fact that the therapeutic dose is higher than the toxic dose (L.Goodman, The Pharmacological Basis of Therapeutics,1980 Ed.L.Goodman, A.Gilman).
The detoxifying action of the ethylene diamino-tetracetic acid is well-known; this product is used as an antidote in poisonings with bi and trivalent metals; its mechanism of action is explained by a chelating process.
The chelating action of the ethylene diaminotetracetic acid and of its salts with various metal ions is dependent upon temperature, pH, and the specific activity of the chelating agent expressed by the stability constant of the resulting complex.
Its antiviral effect has only been proved in in vitro studies on some viral enzymes--the polymerases of viral nucleic acids and the neuraminidase of the A flu virus (Perrin D.D. and Stunzi H., 1981, Pharmac.Ther.22, 255)--whose activity was inhibited by the ethylenediaminotetracetic acids thus, viruses multiplication and their penetration into cells was prevented; however, this chelator has not been as yet used in antiviral human therapy.
The prior art does not mention pharmaceuticals or medicinal compositions meant for antiviral therapy with the ethylene diamino tetracetic acid as their active ingredient.


DISCLOSURE OF INVENTION

The composition as per the present invention, formulated as injectable solution, contains the calcium and sodium salt of ethylene diamino tetracetic acid, associated with calcium gluconate as a source of Ca.sup.2+ ions and an aminoacid (preferably cysteine) or a tripeptide (glutathion); the association ratio of the 3 ingredients is 8 . . . 12; 0.3 . . . 1; 0.05 . . . 0.2.
The advantages of the preparation as per the invention are the following: (Herpes Simplex).
the use of cysteine and the ethylene diamino tetracetic acid in the form of its double salt of calcium and sodium as chelating agents provides an anti-inflammatory and trophic and antiviral effect, ensures a rapid diffusion as well as a uniform distribution in the tissues. Since it is not metabolized in the organism, the product is rapidly eliminated (50% within the first hour from i.p. administration and 100% within 24 hours in rats). cysteine are toxity - free in the dosage prescribed for the above mentioned neurovirotic disorders.
See below 2 concrete examples

REFERENCES:
patent: 4390525 (1983-06-01), Yoshioka et al.
Chem. Abstracts, vol. 87, 1977, 148503h, Citation of Marcialis et al., Exientia, 1977 33(8), 1044-5.
Perrin et al., Pharmac. Ther. 22, pp. 255, 268, 281, 282, 286 and 289 (1981).

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