WO1981001102A1 - Medicine for the treatment of viral infections of the eye and other organs - Google Patents

Medicine for the treatment of viral infections of the eye and other organs Download PDF

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Publication number
WO1981001102A1
WO1981001102A1 PCT/DE1979/000123 DE7900123W WO8101102A1 WO 1981001102 A1 WO1981001102 A1 WO 1981001102A1 DE 7900123 W DE7900123 W DE 7900123W WO 8101102 A1 WO8101102 A1 WO 8101102A1
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Prior art keywords
treatment
viral
viral infections
eye
bacterial
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Application number
PCT/DE1979/000123
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German (de)
French (fr)
Inventor
A Romano
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A Romano
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 A Romano filed Critical A Romano
Priority to PCT/DE1979/000123 priority Critical patent/WO1981001102A1/en
Priority to EP79901504A priority patent/EP0039325A1/en
Priority to DD79216966A priority patent/DD147005A5/en
Priority to IT28000/79A priority patent/IT1126570B/en
Publication of WO1981001102A1 publication Critical patent/WO1981001102A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0048—Eye, e.g. artificial tears

Definitions

  • the invention relates to an agent for the treatment of viral infections of the eye and other organs.
  • Antiviral substances such as interferon have been used to treat viral infections of the eye (Emödi et al., 1974, Jordan, 1974). An improvement in the viral infections was generally achieved, but in many cases a recurrence of an acute viral infection could not be prevented.
  • the aim of the invention is an agent for the treatment of viral infections of the eye and other organs, both for preventive treatment and for the treatment of acute infections, such as those e.g. can be caused by the herpes simplex virus or the adenovirus, which enables effective prophylactic treatment and rapid and very effective control of acute viral infections.
  • the invention proposes an agent for the treatment of viral infections of the eye and other organs from antiviral substance, adjuvants and vehicle, which is characterized in that it also contains, if necessary in the form of a separate preparation, a known antibiotic or several known antibiotics.
  • the agent of the invention enables effective and rapid control of viral infections. It has been found in the context of the invention that there is a very close connection between a bacterial infection and a viral disease, ie that a viral disease is always a bacterial infection or a viral disease is accompanied by such a bacterial infection.
  • bacterial enzymes are present in the focus of the disease. These bacterial enzymes, such as hyaluronidase, impair or prevent the formation of antiviral interferon in the cell, which enables the virus to penetrate and spread.
  • a bacterial infection can be determined in addition to a viral infection and thus the beginning of a viral disease using the following method:
  • the method consists of staining a glucose aminoglycan substrate with toluidine blue (an orthochromatic color) and then decolourising it, thereby obtaining a halo (lightened area) at the reaction site between the substrate and the decomposing enzyme.
  • glucosaminoglycan substrate e.g. Chondroitin sulfate
  • hyaluronidic acid in concentrations of 0.001 °. to 0.11.
  • control plates are prepared:
  • PBS Phoshate Buffer Saline
  • Microplates the Hank material with agarose and the substrate and in addition the standard enzymes hyaluronidase (auferg dertestes) (1 mg / ml or solutions according to a standard card, at one place on the plate.
  • hyaluronidase erythyluronidase
  • a filter paper such as a disc, e.g. the strip for de: or the usual disc for an antibiogram micro capillary tubes.
  • a filter paper such as a disc, e.g. the strip for de: or the usual disc for an antibiogram micro capillary tubes.
  • Components of the agent 1. For local treatment (drops or ointment),
  • Antibiotics Gentamycin sulfate or
  • antibiotics are used for ophthalmic treatment.
  • the amounts used correspond to the usual, but still need to be effective (bak ⁇ terizide minimum effect). In general, the amounts used vary between 3 mcg / ml and 100 mcg / ml.
  • Neomycin sulfate in particular supports the interferon and facilitates its penetration.
  • Metals such as silver, copper, mercury and iodine.
  • Zinc Oxide 0.5% in saline is given.
  • N-acetylcysteine another form of the cysteine group, is also recommended as an interferon stabilizer.
  • Human fibroblastic interferon for local application in a dosage of 1x10 ref units / ml 2 to 6x / day for at least 7 days. It is a saline solution of phosphate buffer (pH 7), which also contains a solution of human albumin (0.3%).
  • Poly I C (polylysine-CA cellulose), dissolved in phosphate buffer (pH 7) in a dosage of 1000 mcg / ml, is stored in a cooling system, for local application 100 to 200 units / 0.1 cm 3 6 to Administered 8x / day for at least 7 days (total therapeutic dose of 5000 to 30000 mcg). A total therapeutic dose of 30 mcg / 70 kg body weight is administered for intravenous use (that is 4000 to 6000 units in 24 hours).
  • the neutralizers listed above should be used a few minutes before the administration of Poly I: C in order to achieve depolarization of the tissue. This depolarization prepares the intrusion of interferon.
  • N-Acetylcysteindextran 0.05 ml / drop.
  • Steroids for local use 0.05% to 0.5% to 1%, 4x / day, for general use 5 to 50 mg / day.
  • the method is required to detect the onset of a viral disease and to begin effective treatment.

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  • Health & Medical Sciences (AREA)
  • Ophthalmology & Optometry (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The medicine for the treatment of viral infections of the eye and other organs made of antiviral substance, adjuvants and vehicles, further contains one or a plurality of known antibiotics, optionally in a separate preparation. The bacterial infections present besides viral infections may then be fought against by means of the antibiotic, thus preventing the formation of bacterial enzymes, such as hyaluronidase, which inhibit the formation of interferon in the cell. The presence of a bacterial infection before and/or during a viral infection may be revealed by the presence of bacterial enzymes before and during the viral desease.

Description

Mittel zur Behandlung von Virusinfektionen des Auges und anderer OrganeAgents for the treatment of viral infections of the eye and other organs
Die Erfindung betrifft ein Mittel zur Behandlung von Virusinfektionen des Auges und anderer Organe.The invention relates to an agent for the treatment of viral infections of the eye and other organs.
Zur Behandlung von Virusinfektionen des Auges wurden bisher schon antivi¬rale Substanzen wie Interferon verwendet (Emödi u.a., 1974, Jordan, 1974). Es wurde damit im allgemeinen eine Besserung der Virusinfektionen erreicht, doch konnte vielfach ein erneutes Auftreten einer akuten VirusInfektion nicht verhindert werden.Antiviral substances such as interferon have been used to treat viral infections of the eye (Emödi et al., 1974, Jordan, 1974). An improvement in the viral infections was generally achieved, but in many cases a recurrence of an acute viral infection could not be prevented.
Ziel der Erfindung ist ein Mittel zur Behandlung von Virusinfektionen des Auges und anderer Organe, und zwar sowohl zur vorbeugenden Behandlung als auch zur Behandlung akuter Infektionen, wie sie z.B. durch den Herpes sim¬plex-Virus oder den Adenovirus hervorgerufen werden, welches eine wirksame prophylaktische Behandlung und eine rasche und sehr wirksame Bekämpfung akuter Virusinfektionen ermöglicht.The aim of the invention is an agent for the treatment of viral infections of the eye and other organs, both for preventive treatment and for the treatment of acute infections, such as those e.g. can be caused by the herpes simplex virus or the adenovirus, which enables effective prophylactic treatment and rapid and very effective control of acute viral infections.
Die Erfindung schlägt ein Mittel zur Behandlung von Virusinfektionen des Auges und anderer Organe aus antiviraler Substanz, Adjuvanzien und Vehicu¬la vor, das dadurch gekennzeichnet ist, daß es außerdem, gegebenenfalls in Form einer gesonderten Zubereitung, ein bekanntes Antibiotikum oder mehrere bekannte Antibiotika enthält.The invention proposes an agent for the treatment of viral infections of the eye and other organs from antiviral substance, adjuvants and vehicle, which is characterized in that it also contains, if necessary in the form of a separate preparation, a known antibiotic or several known antibiotics.
Das Mittel der Erfindung eimöglicht eine wirksame und rasche Bekämpfung von Virusinfektionen. Es wurde nämlich im Rahmen der Erfindung festgestellt, daß ein sehr enger Zusammenhang zwischen einer bakteriellen Infektion und einer Viruserkrankung besteht, d.h. , daß einer Viruserkrankung immer eine bakterielle Infektion vorangeht oder eine Viruserkrankung von einer solchen bakteriellen Infektion begleitet wird. Vor und während einer Viruser krankung sind bakterielle Enzyme beim Krankheitsherd vorhanden. Diese bak teriellen Enzyme, wie die Hyaluronidase, beeinträchtigen bzw. hindern eine Bildung von antiviralem Interferon in der Zelle, wodurch ein Eindringen und ein Ausbreiten des Virus ermöglicht wird.The agent of the invention enables effective and rapid control of viral infections. It has been found in the context of the invention that there is a very close connection between a bacterial infection and a viral disease, ie that a viral disease is always a bacterial infection or a viral disease is accompanied by such a bacterial infection. Before and during a viral disease, bacterial enzymes are present in the focus of the disease. These bacterial enzymes, such as hyaluronidase, impair or prevent the formation of antiviral interferon in the cell, which enables the virus to penetrate and spread.
Im Laboratorium kann eine bakterielle Infektion neben einer Virusinfektio und dadurch der Beginn einer Viruserkrankung nach folgender Methode festge stellt werden:In the laboratory, a bacterial infection can be determined in addition to a viral infection and thus the beginning of a viral disease using the following method:
Die Methode besteht aus dem Anfärben eines Glucos-aminoglycansubstrats mit Toluidinblau (einer orthochromatischen Farbe) und dem darauffolgenden Entfärben, um dadurch einen Halo (aufgehellter Hof) an der Reaktionsstelle zwischen Substrat und dem dies zersetzenden Enzyms zu erhalten.The method consists of staining a glucose aminoglycan substrate with toluidine blue (an orthochromatic color) and then decolourising it, thereby obtaining a halo (lightened area) at the reaction site between the substrate and the decomposing enzyme.
Technische Einzelheiten:Technical details:
Kleine Platten von Mikrogewebekiilturen werden mit folgenden Substanzen angefüllt:Small plates of micro tissue cooling are filled with the following substances:
2 bis 3 cm3von einem Puffer (pH 7 - 8,1) des konzentrierten Materials nach Hank mit kleinsten Mengen Penicillin-Streptσmycin-Mycostati enthält;Contains 2 to 3 cm 3 of a buffer (pH 7-8.1) of the concentrated material according to Hank with the smallest amounts of penicillin-streptσmycin-mycostati;
Agarose 11 in Kochsalzlösung;Agarose 11 in saline;
ein Glucosaminoglycansubstrat, wie z.B. Chondroitinsulfat, in Konzen tration von 0,01%, 0,05% und 0,11 oder Hyaluronidsäure in Konzentrationen von 0,001°. bis 0,11.a glucosaminoglycan substrate, e.g. Chondroitin sulfate, in concentrations of 0.01%, 0.05% and 0.11 or hyaluronidic acid in concentrations of 0.001 °. to 0.11.
Außer den obigen Mikroplatten werden folgende Kontrollplatten vorbereitet:In addition to the microplates above, the following control plates are prepared:
Mikroplatten, die nur Material nach Hank mit 1. Agarose ohne Substra enthalten, oder Mikroplatten, die eine Phoshate-Puffer-Kochsalzlösung (PBS) mit 1. Agarose ohne Substrat enthalten.Microplates containing only Hank 1st Agarose material without substrate or microplates containing Phoshate Buffer Saline (PBS) containing 1st Agarose without substrate.
Mikroplatten, die Material nach Hank mit Agarose und das Substrat und zusätzlich die Standardenzyme Hyaluronidase (aufgear dertestes) (1 mg/ml oder Lösungen nach einer Standardska ten, und zwar an einer Stelle der Platte. An eine andere für Vergleichszwecke, bakterielles Enzym von Tränen in a nach einer Standardskala gebracht.Microplates, the Hank material with agarose and the substrate and in addition the standard enzymes hyaluronidase (auferg dertestes) (1 mg / ml or solutions according to a standard card, at one place on the plate. To another for comparison purposes, bacterial enzyme of tears in a brought on a standard scale.
Mikroplatten, die ausser Agarose und Substrat auch Enz_ tor, wie Heparin, 0,05% oder Dextransulfat in verschier nungen und Lösungen, enthalten.Microplates containing agarose and substrate as well as enz_ tor, such as heparin, 0.05% or dextran sulfate in various solutions and solutions.
Alle Mikroplatten sollen hermetisch verschlossen in e: aufbewahrt werden.All microplates should be kept hermetically sealed in e :.
Technische Methoden für die Gewinnung des Enzyms aus versd" sehen Flüssigkeiten und Geweben, Tränen, Blut, Samen, Corn< und Bakterienkulturen von Infektionsstellen.Technical methods for the extraction of the enzyme from versd "see fluids and tissues, tears, blood, semen, Corn <and bacteria cultures of infection sites.
Das Gewinnen des Materials wird mit einem Filterpap: einer solchen Scheibe, wie z.B. dem Streifen für de: oder der gebräuchlichen Scheibe für ein Antibiogram Mikrokapillarröhren durchgeführt. Jedes gewonnene I- einige oder alle Mikroplatten gebracht und bei Raur Minuten inkubiert. Nachher werden die Filterpapier ben von den Mikroplatten genommen und der AnfärburThe extraction of the material is carried out with a filter paper: such a disc, e.g. the strip for de: or the usual disc for an antibiogram micro capillary tubes. Each I obtained some or all of the microplates brought and incubated at Raur minutes. Afterwards, the filter paper is removed from the microplates and the heating device
Färbungstechnik:Coloring technique:
2 cm3Toluidinblau, 0,11 werden gleichmäßig auf j streut, 5 Minuten dort gehalten und danach mit 7' waschen.2 cm 3 of toluidine blue, 0.11 are sprinkled evenly on j, held there for 5 minutes and then washed with 7 '.
Das Mittel der Erfindung und seine Anwendung wird in c spiel erläutert.The means of the invention and its application is explained in c game.
Beispielexample
Komponenten des Mittels : 1. Zur lokalen Behandlung (Tropfen oder Salbe) ,Components of the agent: 1. For local treatment (drops or ointment),
Antibiotika: Gentamycinsulfat oderAntibiotics: Gentamycin sulfate or
Chloramphenicol oderChloramphenicol or
Cephalotinnatrium (Cephalin) oderCephalotin sodium (cephalin) or
Terramycin oder andere weitere Antibiotika, die dem Antibiogramm nach verwendbar sind.Terramycin or other antibiotics that can be used according to the antibiogram.
Diese Antibiotika werden wegen ihrer direkten antiviralen Wirkung zur ophtalmischen Behandlung eingesetzt. Die angewendeten Mengen entsprechen den üblichen, müssen aber noch wirksam sein können (bak¬ terizide Mindestwirkung) . Im allgemeinen schwanken die angewendeten Mengen zwischen 3 mcg/ml und 100 mcg/ml.Because of their direct antiviral effect, these antibiotics are used for ophthalmic treatment. The amounts used correspond to the usual, but still need to be effective (bak ¬ terizide minimum effect). In general, the amounts used vary between 3 mcg / ml and 100 mcg / ml.
Es wird außerdem die zusätzliche Verwendung von Polymixin B-Sulfate mit/oder Neomycinsulfate in einer Konzentration von 0,25% bis 0,50% empfohlen, und zwar nicht nur wegen der antibakteriellen Wirkung die ser beiden Antibiotika, sondern hauptsächlich wegen derer Fähigkeit, die bakteriellen Enzyme zu neutralisieren. Besonders Neomycinsulfat unterstützt das Interferon und erleichtert das Eindringen desselben.The additional use of polymixin B sulfates with / or neomycin sulfates in a concentration of 0.25% to 0.50% is recommended, not only because of the antibacterial effect of these two antibiotics, but mainly because of their ability to neutralize bacterial enzymes. Neomycin sulfate in particular supports the interferon and facilitates its penetration.
2. Neutralisatoren für bakterielle Enzyme.2. Neutralizers for bacterial enzymes.
a. Polymixin B-Sulfat, Neomycinsulfat,a. Polymixin B sulfate, neomycin sulfate,
Metalle, wie Silber, Kupfer, Quecksilber, ferner Jod. Als Beispiel wird Zinksulfat 0,5% in Kochsalzlösung angegeben.Metals such as silver, copper, mercury and iodine. As an example, zinc sulfate 0.5% in saline is given.
b. Heparinsulfat 0,05%, lokal oder subconjunctival, wie auch allgemein, DEΑE (Diäthhylaminozellulosedextran) in Dosen von 400 mcg/ml/Tag lokal allgemein zur Unterstützung der Inerferoneindringung.b. Heparin sulfate 0.05%, local or subconjunctival, as well as in general, DEΑE (diethylamino cellulose dextran) in doses of 400 mcg / ml / day locally in general to support the inferferone penetration.
c. Eßbare Säure, 0,1 bis 1%, in Kochsalzlösung (pH 7). (Sie ist nicht gleichzeitig mit Metallen zu verwenden) ,c. Edible acid, 0.1 to 1%, in saline (pH 7). (It cannot be used simultaneously with metals),
L-Cystein (freie Base), 1,2% bis 3%, aliphatische Alkohole, die Sulfate enthalten,L-cysteine (free base), 1.2% to 3%, aliphatic alcohols containing sulfates,
N-Acetylcystein (eine weitere Form der Cysteingruppe, wird auch als Interferonstabilisator empfohlen) .N-acetylcysteine (another form of the cysteine group, is also recommended as an interferon stabilizer).
3. Interferon und/oder Initiatoren dafür.3. Interferon and / or initiators for it.
a. Menschliches fibroblastisches Interferon für lokale Anwendung in einer Dosierung von 1x10 ref Einheiten/ml 2 bis 6x/Tag während wenigstens 7 Tagen. Es ist eine Kochsalzlösung von Phosphatpuffer (pH 7) , die auch eine Lösung von menschlichem Albumin (0,3%) enthält.a. Human fibroblastic interferon for local application in a dosage of 1x10 ref units / ml 2 to 6x / day for at least 7 days. It is a saline solution of phosphate buffer (pH 7), which also contains a solution of human albumin (0.3%).
b. Menschliches leukocytisches Interferon für lokale Anwendung in einer DDoossiieenruπng von 1x10 ref Einheiten/ml 2 bis 6x/Tag während wenigstens 7 Tagenb. Human leukocytic interferon for local application in a DDoossiieenruπng of 1x10 ref units / ml 2 to 6x / day for at least 7 days
Beide Substanzen sollen in plastischen Kapillarröhrchen von 0,5 bis 1 ml (= 1 bis 2 Tropfen) für eine einmalige Anwendung in einer Kühlanlage aufbewahrt werden.Both substances should be stored in plastic capillary tubes of 0.5 to 1 ml (= 1 to 2 drops) for a single application in a cooling system.
c. Poly I:C (Polylysin-CA-Zellulose), gelöst in Phosphatpuffer (pH 7) in einer Dosierung von 1000 mcg/ml, wird in einer Kühlanlage aufbewahrt, für lokale Anwendung werden 100 bis 200 Einheiten /0,1 cm36 bis 8x/Tag wenigstens während 7 Tagen verabreicht, (Therapeutische Gesamtdosis von 5000 bis 30000 mcg) . Für die intravenöse Anwendung wird eine therapeutische Gesamtdosis von 30 mcg/70 kg Körpergewicht verabreicht (das sind 4000 bis 6000 Einheiten in 24 Stunden) . Die oben angegebenen Neutralisatoren sind wenige Minuten vor der Verabreichung von Poly I:C anzuwenden, um dadurch eine Depolarisierung des Gewebes zu erreichen. Diese Depolarisierung bereitet das Eindringen von Interferon vor.c. Poly I: C (polylysine-CA cellulose), dissolved in phosphate buffer (pH 7) in a dosage of 1000 mcg / ml, is stored in a cooling system, for local application 100 to 200 units / 0.1 cm 3 6 to Administered 8x / day for at least 7 days (total therapeutic dose of 5000 to 30000 mcg). A total therapeutic dose of 30 mcg / 70 kg body weight is administered for intravenous use (that is 4000 to 6000 units in 24 hours). The neutralizers listed above should be used a few minutes before the administration of Poly I: C in order to achieve depolarization of the tissue. This depolarization prepares the intrusion of interferon.
4. Interferon-Stabilisatoren4. Interferon stabilizers
a. N-Acetylcysteindextran, 0,05 ml/Tropfen.a. N-Acetylcysteindextran, 0.05 ml / drop.
b. Dextran in allen seinen Formen. c. Polyvinylpyrrolidon (Polyvinylpirididon) .b. Dextran in all its forms. c. Polyvinyl pyrrolidone (polyvinyl pyrididone).
5. Zusätzlich zu den vorstehenden Interferon-Stabilisatoren können die fol genden Substanzen bei Infektionen angewendet werden:5. In addition to the above interferon stabilizers, the following substances can be used in infections:
a. Steroide für die lokale Anwendung 0,05% bis 0,5% bis 1%, 4x/Tag, für die allgemeine Anwendung 5 bis 50 mg/Tag.a. Steroids for local use 0.05% to 0.5% to 1%, 4x / day, for general use 5 to 50 mg / day.
b. Indomed als Antiprostaglandimaterial 1% bei lokaler Anwendung, 10 mg bei parenteraler Anwendung.b. Indomed as an antiprostaglandic material 1% when used locally, 10 mg when used parenterally.
c. I.D.TJ. oder Trifluorothymidin in kleinen Mengen, das den Steroiden entgegenwirkt und eine mögliche Reaktivierung des Virus verhindert.c. I.D.TJ. or trifluorothymidine in small amounts, which counteracts the steroids and prevents possible reactivation of the virus.
6. Methode im Laboratorium zur Entdeckung einer bakteriellen Infektion, während eine solche Virale schon existiert.6. Method in the laboratory for the detection of a bacterial infection while such a viral already exists.
a. Die Methode ist erforderlich, um den Anfang einer viralen Krankheit zu erfassen und um eine wirksame Behandlung anzufangen. a. The method is required to detect the onset of a viral disease and to begin effective treatment.

Claims

PatentanspruchClaim
Mittel zur Behandlung von Virusinfektionen des Auges und anderer Organe aus antiviraler Substanz, Adjuvanzien und Vehicula, dadurch gekennzeichnet, daß es außerdem, gegebenenfalls in einer gesonderten Zubereitung, ein bekanntes Antibiotikum oder mehrere bekannte Antibiotika enthält. Agent for the treatment of viral infections of the eye and other organs from antiviral substance, adjuvants and vehicles, characterized in that it also contains, if appropriate in a separate preparation, a known antibiotic or several known antibiotics.
PCT/DE1979/000123 1979-10-19 1979-10-19 Medicine for the treatment of viral infections of the eye and other organs WO1981001102A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
PCT/DE1979/000123 WO1981001102A1 (en) 1979-10-19 1979-10-19 Medicine for the treatment of viral infections of the eye and other organs
EP79901504A EP0039325A1 (en) 1979-10-19 1979-10-19 Medicine for the treatment of viral infections of the eye and other organs
DD79216966A DD147005A5 (en) 1979-10-19 1979-11-16 METHOD FOR DETECTING BACTERIAL INFECTIONS
IT28000/79A IT1126570B (en) 1979-10-19 1979-12-07 PRODUCT FOR THE TREATMENT OF VIRAL INFECTIONS OF THE EYE AND OTHER ORGANS

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Application Number Priority Date Filing Date Title
PCT/DE1979/000123 WO1981001102A1 (en) 1979-10-19 1979-10-19 Medicine for the treatment of viral infections of the eye and other organs
WODE79/00123 1979-10-19

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DD (1) DD147005A5 (en)
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CHEMICAL ABSTRACTS, Band 72, Nummer 9, 2. Marz 1970, (Columbus, Ohio US) A. BILLIAU et al.: "Induction of the interferon mechanism by singlestranded RNA; potentiation by polybasic substances", siehe Seite 236, Zusammenfassung Mr. 41333r, Proc.Soc. Exp.Biol.Med.1969, 132(2), 790-796 (Eng.) *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0080032A2 (en) * 1981-11-20 1983-06-01 Enzo Biochem, Inc. Pharmaceutical preparation for treating herpetic lesions
EP0080032A3 (en) * 1981-11-20 1985-11-13 Enzo Biochem, Inc. Pharmaceutical preparation for treating herpetic lesions

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IT7928000A0 (en) 1979-12-07
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EP0039325A1 (en) 1981-11-11

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