DE2715711A1 - Topical compsn. for viral infections of skin and mucosa - contains heavy metal salt, esp. zinc sulphate, and opt. anti:metabolic virustatics - Google Patents

Topical compsn. for viral infections of skin and mucosa - contains heavy metal salt, esp. zinc sulphate, and opt. anti:metabolic virustatics

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Publication number
DE2715711A1
DE2715711A1 DE19772715711 DE2715711A DE2715711A1 DE 2715711 A1 DE2715711 A1 DE 2715711A1 DE 19772715711 DE19772715711 DE 19772715711 DE 2715711 A DE2715711 A DE 2715711A DE 2715711 A1 DE2715711 A1 DE 2715711A1
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DE
Germany
Prior art keywords
skin
esp
compsn
metal salt
heavy metal
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.)
Withdrawn
Application number
DE19772715711
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German (de)
Inventor
Ernst Mauz
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.)
Robugen GmbH
Original Assignee
Robugen GmbH
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 Robugen GmbH filed Critical Robugen GmbH
Priority to DE19772715711 priority Critical patent/DE2715711A1/en
Publication of DE2715711A1 publication Critical patent/DE2715711A1/en
Withdrawn legal-status Critical Current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
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/245—Bismuth; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/30—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/34—Copper; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/38—Silver; Compounds thereof

Abstract

Pharmaceutical compsn. for topical application for treating virus diseases of the skin and mucous membranes contains (a) a virustatic cpd. of the antimetabolite type, and (b) an Ag, Bi, Cu or Zn salt, in a conventional carrier plus usual additives. The compsn. is esp. formulated as a gel and the pref. active ingredients are ZnSO4 and beta-5-ethyl-2'-deoxyuridine. Used partic. for treating herpes infections. The metal salts are effective against RNA and DNA viruses; do not induce development of resistant strains; are not teratogenic or mutagenic and do not delay regeneration of affected tissue. They also intensify and extend the activity of (I) allowing smaller doses to be used.

Description

Topisch anwendbares Arzneimittel zur Behandlung von Virus-Topically applicable drug for the treatment of viral

erkrankungen der Haut und der Schleimhaut Die Erfindung betrifft topisch anwendbare Arzneimittel zur Behandlung von Viruserkrankungen der Haut und der Schleimhaut auf der Basis eines Schwermetallsalzes und eines antimetabolisch wirkenden Virostatikums.Skin and Mucosal Diseases The invention relates topically Applicable drugs for the treatment of viral diseases of the skin and mucous membranes based on a heavy metal salt and an antimetabolic virostat.

Es ist bekannt, die Lösungen bestimmter Schwermetallsalze für antiseptische Zwecke zu verwenden. Kupferslfat und Zinksulfat wurden früher häufig auch als Brech- oder Atzmittel verwendet. Von einigen Schwermetallsalzen ist außerdem bekannt, daß sie adstringierende Wirkung haben.It is known to use certain heavy metal salts for antiseptic solutions Purposes to use. Copper sulfate and zinc sulfate were often used in the past as or caustic used. It is also known of some heavy metal salts that they have an astringent effect.

Außerdem ist bekannt, daß lokale Erkranken durch Herpesviren mit virostatisch wirksanen Antimetabolltcn bekäpft werden können, die in der Vermehrungsphase ang eifen. s hat sich jedoch herausgestellt, daß einige dieter Chemotherapeutika verschiedene ernste Nachteile besitzen, zum Beispiel können sie die Regeneration des betroffenen Gewebes verzögern; wirken sie zum Teil im Tierversuch teratogen und mutagen; bilden sich resistente Herpesstämme aus und sind sie nicht gegen RNS-Viren wirksam. und innehalb der DNS-Gruppe ist ihre Wirksamkeit bei lokaler Anwendung auf Herpesviren beschränkt.It is also known that local diseases caused by herpes viruses with virostatic effective Antimetabolltcn can be combated, which ang tire. However, some of the chemotherapeutic agents have been found to be different have serious drawbacks, for example they can promote regeneration of the affected Delay tissue; Some of them have a teratogenic and mutagenic effect in animal experiments; form resistant herpes strains and are not effective against RNA viruses. and within the DNS group is its effectiveness when applied locally to herpes viruses limited.

Der Erfindung liegt daher die Aufgabe zugrunde, ein Arzneimittel bereitzustellen, das die obengenannten Nachteile nicht hat.The invention is therefore based on the object of providing a medicament which does not have the disadvantages mentioned above.

Überraschenderweise wurde gefunden, daß die Ionen bzw.Surprisingly, it was found that the ions or

Salze bestimmter Schwermetalle gegen Viren lokal wirksam sind, ohne die obenerwähnten Nachteile zu besitzen. Geeignete Schwermetalle sind Silber, Wismut, Kupfer, besonders ceeignet ist Zink. Man verwendet sie in Form ihrer Salze mit pharmazeutisch verträglichen anorganischen und organischen Säuren. Beispiele für geeignete Anionen sind die Sulfate, Nitrate, Phosphate, Hydrogenphosphate, Car onate, Halogenide, Acetate, Tartrate, Salicylate oder Phenolsulfonate etc.Salts of certain heavy metals are effective locally against viruses without having the disadvantages mentioned above. Suitable heavy metals are silver, bismuth, Copper, zinc is particularly suitable. They are used in the form of their salts with pharmaceuticals compatible inorganic and organic acids. Examples of suitable anions are the sulfates, nitrates, phosphates, hydrogen phosphates, carbonates, halides, Acetates, tartrates, salicylates or phenolsulfonates etc.

Als besonders wirksam und vorteilhaft hat sich Zinksulfat erwiesen. Die Metallsalze werden vorzugsweise zu einem Gel verarbeitet und topisch angewendet.Zinc sulfate has proven to be particularly effective and advantageous proven. The metal salts are preferably made into a gel and applied topically.

Das erfindungsgemäße Arzneimittel zur topischen Behandlung von Viruserkrankungen der Haut und der Schleimhaut besteht daher aus einem üblichen, zu einem Ccl verarbeitbaren Arzneimittelträger, der gegebenenfalls übliche Konservierungsmittel, Stabilisatoren und übliche Arzneimittelzusätze enthalten kann und einem erfindungsgemäßen Metallsalz, insbesondere Zinksulfat. Die Wirkstoffkonzentration, d.h. die Metallsalzkonzentration, des Arzneimittels beträgt im allgemeinen 0,1 bis 3 %, vorzugsweise 0,1 bis 1 t.The medicament according to the invention for the topical treatment of viral diseases the skin and the mucous membrane therefore consists of a conventional one that can be processed into a Ccl Pharmaceutical excipients, any usual preservatives, stabilizers and can contain conventional pharmaceutical additives and a metal salt according to the invention, especially zinc sulfate. The active ingredient concentration, i.e. the metal salt concentration, of the drug is generally 0.1 to 3%, preferably 0.1 to 1%.

Ein geeignetes Verdickungsmittel bzw. ein geeigneter Arzneimittelträger ist eine besonders aufbereitete Methylcellulose, Methylhydroxyäthylcellulose, erhältlich unter der Bezeichnung Tylose MH 4000 Pl (Tylose ist ein der Firma Hoechst geschütztes Warenzeichen). Als Konservierungsmittel kann ebenfalls jedes pharmazeutisch geeignete Konservierungsmittel verwendet werden, sehr brauchba; ist Natrium-äthylmercurithiosalicylat, das in üblicher Konzentration verwendet wird.A suitable thickener or drug carrier A specially prepared methyl cellulose, methyl hydroxyethyl cellulose, is available under the name Tylose MH 4000 Pl (Tylose is a registered trademark of Hoechst Trademark). Any pharmaceutically suitable preservative can likewise be used Preservatives used are very usefulba; is sodium ethyl mercurithio salicylate, which is used in the usual concentration.

Bezüglich des Wirkungsmechanismus des erfindungsgemäßen Arzneimittels nimmt man an, daß die Metallionen mit den.With regard to the mechanism of action of the medicament according to the invention one assumes that the metal ions with the.

SH-Gruppen der Hüllenproteine der Viren reagieren, wobei das Eiweiß des Mantels koaguliert wird und so der Virus schwer geschädigt oder getötet wird. Während Viren gegenüber den üblichen Virostatika oft resistente Stämme bilden, ist eine Resistenzbildung gegen den Angriff der erfindungsgemäßen Metallsalze, insbesondere gegen Zinksalze, unwahrscheinlich.SH groups of the envelope proteins of the viruses react, with the protein of the coat becomes coagulated, seriously damaging or killing the virus. While viruses often form resistant strains to the usual antivirals, is a resistance to attack by the metal salts according to the invention, in particular against zinc salts, unlikely.

Aufgrund ihres besonderen Wirkungsmechanismus wirken die erfindungsgemäSs Arzneimittel sowohl gegen DNS- als auch gegen RNS-Viren.Due to their special mechanism of action, the invention work Medicines for both DNA and RNA viruses.

Wässrige Lösungen der obengenannten Metallsalze sind weniger gut geeignet, da die Konzentration an Metallsalzen so hoch sein müßte, daß nicht nur die Virusproteine, sondern auch das gesunde Gewebe zu stark verätzt würde.Aqueous solutions of the above-mentioned metal salts are less suitable because the concentration of metal salts would have to be so high that not only the virus proteins, but also the healthy tissue would be too severely corroded.

Bei den erfindungsgemäßen Gel-Zubereitungen hingegen kann die Konzentration des Metallsalzes so gewählt werden, daß es zu einer Schädigung der Viren kommt, eine Verätzung des Gewebes jedoch weitgehend vermieden wird.In the case of the gel preparations according to the invention, on the other hand, the concentration can of the metal salt are chosen in such a way that the viruses are damaged, however, corrosion of the tissue is largely avoided.

Wird eines der obengenannten Metallsalze einem Virostatikum auf Antimetabolitbasis zugesetzt, so tritt eine doppelte therapeutische Wirkung ein. Der Antimetabolit verändert die DNS- bzw. RNS-Doppelspirale, während das Metallsalz die Proteinhülle des Virus angreift. Es wird dadurch eine Verstärkung des Virostatikums erreicht. Man kann daher mit niederen Dosierungen auskommen und die Wirkungsbreite wird größer.If one of the above metal salts becomes an antimetabolite-based antiviral agent added, a double therapeutic effect occurs. The antimetabolite changes the DNA or RNA double spiral, while the metal salt changes the protein shell of the virus attacks. Thereby a strengthening of the virostat is achieved. You can therefore get by with lower doses and the range of effects is greater.

Erfindungsgemäß fand man, daß die Kombination eines der oben genannten Metallsalze mit ß-5-Athyl-2'-deoxyuridin und die Anwendung dieser Kombination in Form eines Geles der oben geschilderten Art ein besonders vorteilhaftes und wirksames topisch anwendbares Arzneimittel zur Behandlung von Viruserkrankungen der Haut und der Schleimhaut ergibt. Besonders vorteilhaft ist die Wirkstoffkombination Zinksulfat/ß-5-Äthyl-2'-deoxyuridin. In Arzneimitteln dieser Art beträgt die Konzentration an Metallsalz, insbesondere an Zinksulfat, vorteilhaft 0,1 bis 1 % und die Konzentration an B-5-Athyl-2'-deoxyuridin 0,015 bis 0,5 % , vorteilhaft 0,08 bis 0,3 t.According to the invention it was found that the combination of any of the above Metal salts with ß-5-ethyl-2'-deoxyuridine and the application of this combination in In the form of a gel of the type described above, a particularly advantageous and effective one topically applicable medicinal product for the treatment of viral diseases of the skin and the mucous membrane results. The active ingredient combination zinc sulfate / ß-5-ethyl-2'-deoxyuridine is particularly advantageous. In drugs of this type, the concentration of metal salt, in particular of zinc sulfate, advantageously 0.1 to 1% and the concentration of B-5-ethyl-2'-deoxyuridine 0.015 to 0.5%, advantageously 0.08 to 0.3 t.

Die nachfolgenden Beispiele sollen die Erfindung weiter erläutern.The following examples are intended to explain the invention further.

Beispiel 1 2,5 g Tylose MH 4000 p werden unter kräftigem Rühren mit 50 ml entmineralisiertem Wasser zu einem Ccl verarbeitet. Example 1 2.5 g of Tylose MH 4000 p are with vigorous stirring 50 ml of demineralized water processed into a Ccl.

Dann wird die Lösung von 1,0 g ZnSO4-7H2O und 2 mg Thimerosal (Natrium-äthyl-mercurithiosalicylat) in 50 ml entmineralisiertem Wasser zugegeben und nochmals durchgerührt.Then the solution of 1.0 g of ZnSO4-7H2O and 2 mg of thimerosal (sodium ethyl mercurithiosalicylate) added in 50 ml of demineralized water and stirred again.

Man erhält ein stabiles, gebrauchsfertiges Cel, das zum Beispiel bei der lokalen Behandlung von He^peseri;rar};ungen im Mundrand-, Lippen- oder Augenbereich in kürzester Zeit alle Krankheitserscheinungen beseitigt.A stable, ready-to-use cel is obtained, which can be used, for example, in the local treatment of he ^ peseri; rar}; ungen in the area of the mouth, lips or eyes eliminates all symptoms of illness in the shortest possible time.

Beispiel 2 2,5 g eines üblichen Verdickungsmittels, z.B. Methylcellulose, werden unter kräftigem Rühren - wie in Beispiel 1 - mit 50 ml entmineralisiertem Wasser zu einem Ccl verarbeitet. Example 2 2.5 g of a common thickening agent, e.g. methyl cellulose, are with vigorous stirring - as in Example 1 - with 50 ml of demineralized Water processed into a Ccl.

Dann wird die Lösung von 1,0 g ZnSO4 7H2O, 2 mg Thimerosal und 0,15 g B-5-Äthyl-2'-deoxyuridin in 50 ml entmineralisiertem Wasser zugegeben und nochmals durchgerührt. Man erhält ein stabiles Gel, das bei lokaler Anwendung gegen Herpeserkrankungen z.B. im Lippenbereich noch rascher als das Mittel des Beispiels 1 alle Krankheitserscheinungen beseitigt.Then the solution of 1.0 g of ZnSO4 7H2O, 2 mg of thimerosal and 0.15 g of B-5-ethyl-2'-deoxyuridine in 50 ml of demineralized water are added and again stirred. A stable gel is obtained which, when applied locally, against herpes diseases e.g. in the lip area even faster than the remedy in Example 1, all symptoms of the disease eliminated.

Claims (4)

Patentansprüche 1. Topisch anwendbares Arzneimittel zur Behandlung 5 r Viruserkrankungen der Haut und der Schlelmhaut, dadurch gekennzeichnet, daß es ein Virosüatikum auf An; cabolitbasis und ein Silber-, Wismuth-, Kupfer- oder Zinksalz in einem üblichen Arzneimittelträger neben üblischen Zusätzen enthält. Claims 1. Topically applicable medicament for treatment 5 r viral diseases of the skin and the mucous membrane, characterized in that it a Virosüatikum on; cabolite and a silver, bismuth, copper or Contains zinc salt in a common excipient in addition to common additives. 2. Arzneimittel nach Anspruch 1 in Form eines Geles.2. Medicament according to claim 1 in the form of a gel. 3. Arzneimittel nach Anspruch 1, gekennzeichnot durch die Wirkstoffkombination Zinksulfat/ß-5-Äthyl-2'-deoxyuridin.3. Medicament according to claim 1, gekennzeichnot by the active ingredient combination Zinc sulfate / ß-5-ethyl-2'-deoxyuridine. 4. Topisch anwendbares Arzneimittel zur Behandlung von Viruserkrankungen der Haut und der Schleimhaut, bestehend aus einem in Gelform vorliegenden lochen Arzneimittelträger, Zinksulfat und einem üblichen Arzneimittel-Konservierungsmittel.4. Topically applicable drug for the treatment of viral diseases the skin and the mucous membrane, consisting of a hole in gel form Excipient, zinc sulfate and a common drug preservative.
DE19772715711 1977-04-07 1977-04-07 Topical compsn. for viral infections of skin and mucosa - contains heavy metal salt, esp. zinc sulphate, and opt. anti:metabolic virustatics Withdrawn DE2715711A1 (en)

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Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0045282A2 (en) * 1980-07-30 1982-02-03 Ciba-Geigy Ag Antiherpes lipstick and its use in treating lips and other face parts attacked by herpes hominis
US4465666A (en) * 1977-06-17 1984-08-14 Ciba-Geigy Corporation New pharmaceutical preparations
EP0206692A2 (en) * 1985-06-14 1986-12-30 Ed. Geistlich Söhne Ag Für Chemische Industrie Topically administrable pharmaceutical compositions
US4661354A (en) * 1984-06-21 1987-04-28 Finnerty Edmund F Topical treatment of herpes simplex with a zinc sulfate-camphor water solution
EP0287204A2 (en) * 1987-02-25 1988-10-19 The Trustees of Columbia University in the City of New York Silver sulfadiazine useful for inhibiting the transmission of the aids virus
FR2740335A1 (en) * 1995-10-26 1997-04-30 Oreal USE OF SALT OF LANTHANIDE, LITHIUM, TIN, ZINC, MANGANESE OR YTTRIUM AS ANTAGONIST OF SUBSTANCE P
FR2751544A1 (en) * 1996-07-23 1998-01-30 Jacob Michel Henri Jean Compositions containing copper or zinc sulphate
WO2001028338A2 (en) * 1999-10-19 2001-04-26 The Procter & Gamble Company Antimicrobial compositions comprising a benzoic acid analog and a metal salt
WO2001028340A2 (en) * 1999-10-19 2001-04-26 The Procter & Gamble Company Antimicrobial compositions comprising a dicarboxylic acid and a metal salt
WO2001028339A2 (en) * 1999-10-19 2001-04-26 The Procter & Gamble Company Antimicrobial compositions comprising a biologically active organic acid
WO2001028337A3 (en) * 1999-10-19 2001-10-18 Procter & Gamble Antiviral compositions for tissue paper

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3065139A (en) * 1953-11-12 1962-11-20 Astra Ab Anti-infectant topical preparations
DE2517413A1 (en) * 1974-05-02 1975-11-13 Draco Ab Dermatological agents contg. zinc salts or complexes - for treating e.g. acne or seborrhoea
DE2545194A1 (en) * 1974-10-28 1976-04-29 Morelle METAL COMPOUNDS AND THEIR USES TO TREAT METAL DEFECTS
DE2529033A1 (en) * 1975-06-28 1977-01-20 Robugen Gmbh Oral medicament to combat dermatoses caused by zinc insufficiency - contains ion exchanger bonded zinc to effect delayed release in and prevent irritation of the gastro-intestinal tracts

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3065139A (en) * 1953-11-12 1962-11-20 Astra Ab Anti-infectant topical preparations
DE2517413A1 (en) * 1974-05-02 1975-11-13 Draco Ab Dermatological agents contg. zinc salts or complexes - for treating e.g. acne or seborrhoea
DE2545194A1 (en) * 1974-10-28 1976-04-29 Morelle METAL COMPOUNDS AND THEIR USES TO TREAT METAL DEFECTS
DE2529033A1 (en) * 1975-06-28 1977-01-20 Robugen Gmbh Oral medicament to combat dermatoses caused by zinc insufficiency - contains ion exchanger bonded zinc to effect delayed release in and prevent irritation of the gastro-intestinal tracts

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Biochem. Pharmacol. 24, 1975, S. 1073-1078 *
The Pharmacological Basis of Therapeutics, 4. Ed., The Macmillan Co., London, 1970, S. 967-969 *

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4465666A (en) * 1977-06-17 1984-08-14 Ciba-Geigy Corporation New pharmaceutical preparations
EP0045282A2 (en) * 1980-07-30 1982-02-03 Ciba-Geigy Ag Antiherpes lipstick and its use in treating lips and other face parts attacked by herpes hominis
EP0045282A3 (en) * 1980-07-30 1982-09-08 Ciba-Geigy Ag Antiherpes lipstick and its use in treating lips and other face parts attacked by herpes hominis
US4661354A (en) * 1984-06-21 1987-04-28 Finnerty Edmund F Topical treatment of herpes simplex with a zinc sulfate-camphor water solution
EP0206692A2 (en) * 1985-06-14 1986-12-30 Ed. Geistlich Söhne Ag Für Chemische Industrie Topically administrable pharmaceutical compositions
EP0206692A3 (en) * 1985-06-14 1988-07-27 Ed. Geistlich Söhne Ag Für Chemische Industrie Topically administrable pharmaceutical compositions
EP0287204A2 (en) * 1987-02-25 1988-10-19 The Trustees of Columbia University in the City of New York Silver sulfadiazine useful for inhibiting the transmission of the aids virus
EP0287204A3 (en) * 1987-02-25 1990-04-11 The Trustees of Columbia University in the City of New York Silver sulfadiazine useful for inhibiting the transmission of the aids virus
FR2740335A1 (en) * 1995-10-26 1997-04-30 Oreal USE OF SALT OF LANTHANIDE, LITHIUM, TIN, ZINC, MANGANESE OR YTTRIUM AS ANTAGONIST OF SUBSTANCE P
EP0770392A3 (en) * 1995-10-26 1997-05-07 L'oreal Use of salts of lanthanide, tin, zinc, manganese, yttrium, cobalt, strontium in a pharmaceutical composition
FR2751544A1 (en) * 1996-07-23 1998-01-30 Jacob Michel Henri Jean Compositions containing copper or zinc sulphate
WO2001028338A2 (en) * 1999-10-19 2001-04-26 The Procter & Gamble Company Antimicrobial compositions comprising a benzoic acid analog and a metal salt
WO2001028340A2 (en) * 1999-10-19 2001-04-26 The Procter & Gamble Company Antimicrobial compositions comprising a dicarboxylic acid and a metal salt
WO2001028339A2 (en) * 1999-10-19 2001-04-26 The Procter & Gamble Company Antimicrobial compositions comprising a biologically active organic acid
WO2001028338A3 (en) * 1999-10-19 2001-09-13 Procter & Gamble Antimicrobial compositions comprising a benzoic acid analog and a metal salt
WO2001028340A3 (en) * 1999-10-19 2001-09-13 Procter & Gamble Antimicrobial compositions comprising a dicarboxylic acid and a metal salt
WO2001028339A3 (en) * 1999-10-19 2001-09-13 Procter & Gamble Antimicrobial compositions comprising a biologically active organic acid
WO2001028337A3 (en) * 1999-10-19 2001-10-18 Procter & Gamble Antiviral compositions for tissue paper

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