WO1994027436A1 - Conservateurs presentant une efficacite antimicrobienne amelioree - Google Patents

Conservateurs presentant une efficacite antimicrobienne amelioree Download PDF

Info

Publication number
WO1994027436A1
WO1994027436A1 PCT/US1994/005693 US9405693W WO9427436A1 WO 1994027436 A1 WO1994027436 A1 WO 1994027436A1 US 9405693 W US9405693 W US 9405693W WO 9427436 A1 WO9427436 A1 WO 9427436A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
quaternary ammonium
group
paraben
antimicrobial
Prior art date
Application number
PCT/US1994/005693
Other languages
English (en)
Inventor
Benedict T. Decicco
James Kevin Keeven
Original Assignee
Decicco Benedict T
James Kevin Keeven
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 Decicco Benedict T, James Kevin Keeven filed Critical Decicco Benedict T
Publication of WO1994027436A1 publication Critical patent/WO1994027436A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/41—Amines
    • A61K8/416—Quaternary ammonium compounds
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N33/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds
    • A01N33/02—Amines; Quaternary ammonium compounds
    • A01N33/12—Quaternary ammonium compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/37—Esters of carboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L12/00—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor
    • A61L12/08—Methods or apparatus for disinfecting or sterilising contact lenses; Accessories therefor using chemical substances
    • A61L12/14—Organic compounds not covered by groups A61L12/10 or A61L12/12
    • A61L12/143—Quaternary ammonium compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/005—Antimicrobial preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/51—Chelating agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/52—Stabilizers
    • A61K2800/524—Preservatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/59—Mixtures

Definitions

  • the invention is generally related to preservatives used in solutions such as nasal sprays, eye and contact lens solutions, shampoos, liquid cold formulations, and other health care products. More particularly, the invention is directed to particular combinations of compounds which have synergistic antimicrobial activity and enhanced speed of kill.
  • Quaternary ammonium compounds such as benzalkonium chloride (BAK) and cetyl pyridinium chloride (CPC) have been used for many years as preservatives.
  • BAK benzalkonium chloride
  • CPC cetyl pyridinium chloride
  • U.S. Patents 2,694,663 and 2,666,010 to Stayner describe the use of quaternary ammonium compounds as germicidal and microbicidal agents
  • U.S. Patent 2,295,505 to Shelton discloses the use of cetyl quaternary ammonium compounds for controlling microorganisms.
  • BAK and CPC continue to be the antimicrobial agents of choice in a wide variety of solutions.
  • Patent 4,474,748 describe a disinfectant solution and a medication, respectively, and both patents note that BAK and CPC can be employed in solution as antimicrobial agents.
  • a significant problem with BAK and CPC is that they can be very irritating to eyes or other tissues when used in a solution at concentrations greater than 0.01% by weight of the solution.
  • BAK and CPC are ineffective against some microorganisms when employed at lower concentrations (e.g., less than 50 ppm), often leading to product contamination.
  • prior art formulations which employ BAK and CPC have an inherent trade-off between irritability and effectiveness.
  • preservatives such as ethylenediaminetetraacetic acid (EDTA) , benzyl alcohol (BA) , thimerosal, chlorhexidine gluconate (CHG) , and polyaminopropyl biguanide (PAPB) , also cause irritation problems.
  • EDTA ethylenediaminetetraacetic acid
  • BA benzyl alcohol
  • CHG chlorhexidine gluconate
  • PAPB polyaminopropyl biguanide
  • compositions with highly irritable preservatives have difficulty in gaining market acceptance, they also pose significant health problems.
  • Many investigators in the contact lens field have suggested using alternatives to BAK because of irritation to the patient's eye.
  • Nasal sprays, liquid cold formulations, shampoos, and other health care products would also suffer from irritability problems.
  • a preservative system's ability to pass the U.S. Pharmacopeia (USP) Preservative Effectiveness Test does not guarantee that the product will remain free of contamination, and such contamination is common with some products that have passed the USP test. In-use testing and the use of "tough" product isolates should be employed to help ensure that a preservative system will be effective under real world conditions.
  • USP U.S. Pharmacopeia
  • the quaternary ammonium compounds contemplated by this invention include BAK and CPC as well as other related quaternary ammonium compounds including substituted benzalkonium compounds such as alkyldimethylethylbenzylammonium chloride or heteroaro atic ammonium salts, twin chain quats like dioctyl dimethyl ammonium bromide, bisquaternary ammonium salts such as triclobisonium chloride, polymeric quaternary ammonium compounds such as polyquaternium, and tri-quaternary phosphate esters such as monoquat PTC, etc. Combinations of two or more of the quaternary ammonium compounds could also be employed in the preservative systems of this invention.
  • the compounds used in combination with quaternary ammonium compounds include methyl paraben and other parabens such as ethyl, propyl and butyl paraben, alcohols such as benzyl alcohol and phenylethyl alcohol, and hydrophobic chelators such as phenanthroline and its derivatives such as methyl, nitro, and chlorophenanthroline, thenoyltrifluoroacetone, hydroxyquinoline and derivatives, bipyridine, picolinic acid, and dipicolinic acid.
  • paraben and other parabens such as ethyl, propyl and butyl paraben
  • alcohols such as benzyl alcohol and phenylethyl alcohol
  • hydrophobic chelators such as phenanthroline and its derivatives such as methyl, nitro, and chlorophenanthroline, thenoyltrifluoroacetone, hydroxyquinoline and derivatives, bipyridine, picolinic acid, and dipicolinic acid.
  • the preservative systems were tested against Staphylococcus aureus 6538, which is a standard tester strain approved for preservative efficacy testing by the USP and British Pharmacopeia (BP) .
  • the preservative systems were also tested against Pseudo onas cepacia 25416 and Serratia marcescens 48, which are rigorous or "tough" environmental organisms.
  • P. cepacia and S. marcescens represent the most potent challenge to preserved formulations and, in recent years, have been common causes of product contamination. Hence, effective preservatives will need to kill these organisms even though they are not currently required for standardized testing.
  • An "adapted" bacterium is one that has been grown in the presence of low levels of an antimicrobial agent and can survive in solutions containing the antimicrobial agent at levels that would kill unadapted bacteria of the same strain.
  • the ability to kill "adapted" S. marcescens demonstrates the superior efficacy of the preservative systems contemplated by this invention.
  • the preservative system for contact lenses have a three log kill of the test microorganism within six hours and that no viable microorganisms be present after twenty four hours contact with the preservative.
  • the U.S. also has a regulatory trend towards more rapid killing.
  • the lowest BAK concentration generally used in current contact lens solutions is 40 ppm. Products containing this level of BAK can be contaminated by tough Pseudomonas species and S. marcescens . Many eye care solutions use as much as 100 ppm BAK to increase antimicrobial activity; however, this level of BAK causes eye irritation.
  • Methyl paraben (MP) is a preservative that is commonly used in cosmetics and food products at concentrations ranging from 0.1 to 1.0%. Methyl paraben is not currently used in contact lens solutions.
  • Tables 1 through 5 provide test data which demonstrate the antimicrobial effectiveness of a preservative system which includes a combination of MP and BAK in aqueous solutions of phosphate buffered saline (PBS, 0.025M potassium phosphate, 0.7% wt/wt NaCl) at near neutral pH conditions ranging from pH 6 to pH 8.
  • PBS phosphate buffered saline
  • BAK benzalkonium chloride
  • OxlO 3 1 .
  • OxlO 4 1.3X10 2 ⁇ 10 lday 7.
  • Table 1 shows that solutions containing BAK alone, at concentrations as high as 20 ppm, were not effective in killing the tough P. cepacia microorganism. Solutions having only MP at higher concentrations (0.1%) were effective against P. cepacia ; however, the speed of kill with these solutions was unacceptable. Specifically, it took one to three days to achieve a three log reduction in viable microorganisms with MP alone, whereas it
  • Table 1 shows that solutions containing a combination of BAK and MP had an enhanced, synergistic killing capacity. Note particularly that in solution at pH 7, a three log reduction in viable P. cepacia occurred after six hours when the solution had as little as 0.05% MP and 10 ppm BAK. At both pH 6 and pH 8, a three log reduction occurred after six hours in a solution containing 0.1 % MP and as little as 5 ppm BAK.
  • Table 2 shows that the MP and BAK combination was highly effective at killing S. aureus .
  • Tables 3 and 4 show that adding EDTA to the preservative combination of MP and BAK has only a very limited effect on microorganism killing activity. However, EDTA is often added to preservative combinations because of its known effectiveness against P. aeruginosa . Comparing Tables 1 and 3, it can be seen that a three log kill of P. cepacia after six hours exposure was achieved with solutions containing 0.05% MP and 10 ppm BAK, with and without 0.1% EDTA. In addition, it is noted from Table 3 that a combination of 0.1% wt/wt EDTA and even 20 ppm BAK, without any MP, was ineffective against the tough P. cepacia bacterium.
  • preservative for P. cepacia is an important measure of the preservative's effectiveness. Furthermore, Table 2 demonstrates that solutions with low levels of BAK, without EDTA or MP, are capable of killing S. aureus at an effective rate.
  • the "adapted" S. marcescens strains reported in Table 5 were produced by growth of the bacteria in a 10% dilution of 0.1%MP + 0.1% EDTA + 20 ppm BAK in 1 g/1 trypticase soy broth (TSB) .
  • Table 5 demonstrates that preservative systems containing a combination of MP and BAK and EDTA are highly effective against both adapted and unadapted strains of S. marcescens .
  • As little as 5 ppm BAK were required in the preservative system to achieve a three log kill of the adapted and unadapted S. marcescens within six hours. Neither 0.1% methyl paraben nor 20 ppm BAK showed any significant effect when used alone.
  • Tables 1 through 5 demonstrate that the combination of MP and BAK provides for a preservative system with a synergistically enhanced killing capacity. While Tables 1 through 5 show test results for formulations having a pH between pH6 and pH 8, similar results would be expected within the pH range of pH 5 to pH 9.
  • TTFA is a hydrophobic chelating compound. Prior to this invention, no preservative activity was known to exist for TTFA. Table 6 shows that there is a synergistic killing activity against a variety of microorganisms when TTFA is used in combination with BAK. The bacteria and fungi tested against this combination include A. niger 19606, S. aureus 14
  • S. marcescens 48 P. cepacia 25416, P. aerugri-nosa 9027, and C. albicans 10231.
  • S. aureus; A. niger, P. aeruginosa, and C. albicans are standard USP and BP preservative efficacy test microorganisms.
  • S. marcescens and P. cepacia are bacteria which are difficult to kill and are the source of contamination in many health care products.
  • Table 6 demonstrates a synergy in terms of killing capacity and speed of kill when TTFA is used in combination with BAK against a wide variety of microorganisms, both bacteria and fungi. Note particularly the sixth section of Table 6 where solutions inoculated with 10* colony forming units of the two tough to kill bacteria, P. cepacia and S . marcescens , experienced much more than a three log kill within six hours time, and where solutions 15a
  • Phenanthroline like TTFA, is a hydrophobic chelator compound. Table 7 demonstrates that when phenanthroline is used alone, or when the quaternary ammonium salts BAK or CPC are used alone, they are ineffective against P. cepacia 25416; however, preservative systems having a combination of phenanthroline and BAK or CPC are very effective.
  • Table 7 shows that when 0.1% phenanthroline is used with as little as 10 ppm BAK or as little as 5 ppm CPC, a three log kill is achieved within six hours for a PBS solution inoculated with 10* cfu of P. cepacia .
  • Benzyl alcohol has been used as a preservative in health care products such as contact lens solutions.
  • One commercial contact lens solution currently uses 0.1% benzyl alcohol; however, 0.1% benzyl alcohol has virtually no antimicrobial effect against P. cepacia after three days exposure, even in the presence of 0.1% EDTA (see Table 8 below).
  • Table 8 also shows that when a quaternary ammonium compound such as benzalkonium chloride is used at 10 or 20 ppm, with 0.1% EDTA, little if any killing of P. cepacia occurs in three days, but when benzyl alcohol, EDTA and 20 ppm BAK are used together, more than a three log kill occurs in one day and a complete kill is observed in three days.
  • Phenylethyl alcohol has not been used as a preservative in health care products such as contact lens solutions.
  • An effect similar to benzyl alcohol is shown in Table 8 with phenylethyl alcohol, except that the killing effect of the combination is even greater.
  • Table 8 shows that when alcohols such as a benzyl and phenylethyl 18
  • alcohol are used in combination with low concentrations of quaternary ammonium compounds such as BAK, they can provide effective preservative activity.
  • Tables 1-8 demonstrate a synergistic killing activity when a quaternary ammonium compound is used in combination with a paraben, hydrophobic chelator, or alcohol compound.
  • Test data have been presented for combinations which include either BAK and CPC; however, other related quaternary ammonium compounds and combinations of two or more quaternary ammonium compounds could be used in combination with the paraben, hyrdophobic chelator, or alcohol compound.
  • Suitable alternative quaternary ammonium compounds to BAK and CPC include substituted benzalkonium compounds such as alkyldimethylethylbenzylammonium chloride or heteroatomic ammonium salts, twin chain quats like dioctyl dimethyl ammonium bromide, 19
  • the concentration of the quaternary ammonium compound can vary depending on the compound chosen. For example, some of the polyquats may be effective in the combined preservative system at levels as low as 1-4 ppm, while some monoquats may need to be present in the combined preservative system at levels of 100 ppm or greater. Preliminary data suggest that when Monoquat PTC at a concentration of 100 ppm is combined with methyl paraben, the combined preservative system has a synergistic killing capability for P. cepacia . The synergistic microorganism killing activity achieved when used in combination with a paraben, hydrophobic chelator, or alcohol compound allows lower concentrations of the quaternary ammonium compound to be used, thereby reducing user irritation and health risks.
  • Tables 1-5 demonstrate the efficacy of methyl paraben in the preservative combinations, and it should be understood similar results could be achieved with other parabens such as ethyl, propyl and butyl parabens.
  • Table 6 demonstrates the efficacy of TTFA and Table 7 demonstrates the efficacy of phenanthroline in the preservative combinations.
  • Table 8 demonstrates the efficacy of alcohols such as phenylethyl and benzyl alcohol in the preservative combinations.
  • chlorophenanthroline can be used in combination with the quaternary ammonium compound within the practice of this invention.
  • the preservative systems of this invention can be used in aqueous solutions such as contact lens solutions and other eye care products, nasal sprays, mouth washes, medical lavage fluids and disinfectants, shampoos, cold medicines, as well as other saline injectible medicines. These types of health care products typically have a neutral or near neutral pH (e.g., pH 5-pH 9). As can be seen from Tables 1-8, the preservative systems of the present invention are contemplated for use in solutions having a pH ranging from pH 5 to pH 9. While the preservative systems were mainly tested against bacteria, it should be understood that they would be effective against molds and yeasts as demonstrated in Table 6.
  • a contact lens solution or eye care formulation including: water; sodium chloride; buffering agents such as sodium and potassium phosphate; viscosity increasing agents such as polyvinyl alcohol; wetting agents;
  • a quaternary ammonium compound selected from the group consisting of BAK, CPC, other related quaternary ammonium compounds including substituted benzalkonium compounds such as alkyldimethylethylbenzylammonium chloride or heteroaromatic ammonium salts, twin chain quats like dioctyl dimethyl ammonium bromide, bisquaternary ammonium salts such as triclobisonium chloride, polymeric quaternary ammonium compounds such as polyquaternium, and tri-quaternary phosphate esters such as Monoquat PTC, etc.; and, alternatively
  • a paraben selected from the group consisting of methyl, ethyl, propyl and butyl parabens,
  • a nasal spray including: water; a therapeutically acceptable amount, e.g., 1-
  • a bronchodilator (albuterol, beclomethasone dipropionate, chromolyn sodium, etc.), an analgesic, an antiinflammatory (e.g., ipratropium, atropine methonitrate, exogenous opioid agonists, alpha adrenergic agonists, antihistamines including chlorpheniramine, prostaglandin blockers and antagonists, leukotriene blockers and antagonists, parasympathetic blockers and antagonists, interleukin blockers and antagonists, and nonsteroidal antiinflammatory agents including naproxen and ibuprophen) , antiviral (e.g., inteferons, interferon inducers, capsid binding agents, benzoimidazoles, 1'-methyl spiro(adamantane-2,3-pyrrolidine)maleate, isatin thiosemicarbazone, fusidic acid, substituted trizainoindoles, 2,
  • steroid e.g., triamcinolone, etc.
  • a quaternary ammonium compound selected from the group consisting of BAK, CPC, other related quaternary ammonium compounds including substituted benzalkonium compounds such as alkyldimethylethylbenzylammonium chloride or heteroaromatic ammonium salts, twin chain quats like dioctyl dimethyl ammonium bromide, bisquaternary ammonium salts such as triclobisonium chloride, polymeric quaternary ammonium compounds such as polyquaternium, and tri-quaternary phosphate esters such as Monoquat PTC, etc.; and alternatively
  • a paraben selected from the group consisting of methyl, ethyl, propyl and butyl parabens,
  • concentration range of the quaternary ammonium compound can be 24
  • a cough or cold formulation including: water; expectorants including guaifenesin, antihistamines including chlorpheniramine and triprolidine hydrochloride, cough suppressants including dextromethorphan hydrobromide, analgesics including acetaminophen, decongestants including phenylpropanolamine hydrochloride and pseudoephedrine hydrochloride, 1-50 ppm of a quaternary ammonium compound selected from the group consisting of BAK, CPC, other related quaternary ammonium compounds including substituted benzalkonium compounds such as alkyldimethylethylbenzylammonium chloride or heteroaromatic ammonium salts, twin chain quats like dioctyl dimethyl ammonium bromide, bisquaternary ammonium salts such as triclobisonium chloride, polymeric quaternary ammonium compounds such as polyquaternium, and tri-quaternary phosphate esters such as Mono
  • a paraben selected from the group consisting of methyl, ethyl, propyl and butyl parabens,
  • a hydrophobic chelator selected from the group consisting of phenanthroline and its derivatives methyl and chlorophenanthroline, thenoyltrifluoroacetone, hydroxyquinoline, bypyridine, picolinic acid, and dipicolinic acid, the solution having a pH ranging between pH 5 and pH 9.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Birds (AREA)
  • Emergency Medicine (AREA)
  • Agronomy & Crop Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dermatology (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

Conservateur comprenant un niveau non irritant d'un composé d'ammonium quaternaire, tel que chlorure de benzalkonium ou chlorure de cétylpyridinium et soit un parabène, un chélatant hydrophobe, soit un composé alcoolique. La combinaison des deux composés permet d'atteindre une efficacité de destruction synergique contre des bactéries de contrôle, des bactéries persistantes et des bactéries adaptées, ainsi que contre des levures et des moisissures. Ladite combinaison permet également d'améliorer la rapidité de destruction.
PCT/US1994/005693 1993-05-20 1994-05-20 Conservateurs presentant une efficacite antimicrobienne amelioree WO1994027436A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US6447093A 1993-05-20 1993-05-20
US08/064,470 1993-05-20

Publications (1)

Publication Number Publication Date
WO1994027436A1 true WO1994027436A1 (fr) 1994-12-08

Family

ID=22056218

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1994/005693 WO1994027436A1 (fr) 1993-05-20 1994-05-20 Conservateurs presentant une efficacite antimicrobienne amelioree

Country Status (1)

Country Link
WO (1) WO1994027436A1 (fr)

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2757402A1 (fr) * 1996-12-24 1998-06-26 Oreal Systeme conservateur et son utilisation dans une composition cosmetique ou pharmaceutique
US5972358A (en) * 1998-01-20 1999-10-26 Ethicon, Inc. Low tack lotion, gels and creams
US5997893A (en) * 1998-01-20 1999-12-07 Ethicon, Inc. Alcohol based anti-microbial compositions with cosmetic appearance
US6022551A (en) * 1998-01-20 2000-02-08 Ethicon, Inc. Antimicrobial composition
EP1080715A2 (fr) * 1999-08-05 2001-03-07 Bode Chemie GmbH & Co. Combinaison de principes actifs et compositions pour le soin des pieds le contenant
US6248343B1 (en) 1998-01-20 2001-06-19 Ethicon, Inc. Therapeutic antimicrobial compositions
WO2002069710A1 (fr) * 2001-03-01 2002-09-12 Lonza, Inc. Melanges conservateurs contenant des composes ammomium quaternaires
WO2004000373A1 (fr) * 2002-06-22 2003-12-31 Ecolab Inc. Concentre aqueux pour la desinfection de surfaces
WO2005097960A1 (fr) * 2004-04-07 2005-10-20 Advanced Medical Optics, Inc. Chlorure de cetylpyridinium utilise en tant qu'agent antimicrobien dans des compositions ophtalmiques
WO2005112907A2 (fr) * 2004-05-14 2005-12-01 Lifetech Usa, Inc. Agents non toxiques permettant de detruire e. coli et d'autres micro-organismes posant des problemes
WO2009047584A1 (fr) * 2007-10-11 2009-04-16 Hatchtech Pty. Ltd. Compositions de combinaison et procédés d'utilisation de celles-ci pour lutter contre une infestation
WO2016098965A1 (fr) * 2014-12-15 2016-06-23 코오롱생명과학 주식회사 Composition antiseptique et son utilisation
CN106119028A (zh) * 2016-07-05 2016-11-16 吴俊娟 一种三黄芎参酒
WO2018083675A1 (fr) * 2016-11-07 2018-05-11 Jubilant Life Sciences Limited Compositions antimicrobiennes synergiques
CN110290703A (zh) * 2016-12-16 2019-09-27 弗特鲁斯控股有限责任公司 季胺制剂及其用途
EP3496540A4 (fr) * 2016-08-11 2020-07-15 Ecolab USA Inc. Interaction entre des composés quaternaires antimicrobiens et des tensioactifs anioniques
US11406103B2 (en) 2016-03-01 2022-08-09 Ecolab Usa Inc. Sanitizing rinse based on quat-anionic surfactant synergy

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2694663A (en) * 1950-09-05 1954-11-16 California Research Corp Synergistic microbicidal compositions
US4474748A (en) * 1979-09-26 1984-10-02 Johnson & Johnson Medicaments potentiated with phenyl alkanols

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2694663A (en) * 1950-09-05 1954-11-16 California Research Corp Synergistic microbicidal compositions
US4474748A (en) * 1979-09-26 1984-10-02 Johnson & Johnson Medicaments potentiated with phenyl alkanols

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, Volume 113, No. 10, issued 03 September 1990, MORITA et al., "Ophthalmic Solution Containing Benzalkonium Chloride, P-Hydrobenzoate Esters, and Chelating Agents", Abstract No. 113:84881a. *
CHEMICAL ABSTRACTS, Volume 76, No. 15, issued 10 April 1972, RICHARDS et al., "Phenylethanol Enhancement of Preservatives Used in Ophthalmic Preparations", Abstract No. 81660j. *
CHEMICAL ABSTRACTS, Volume 80, No. 13, issued 01 April 1974, RICHARDS et al., "Enhancement of Benzalkonium Chloride and Chlorhexidine Acetate Activity Against Pseudomonas Aeruginosa by Aromatic Alcohols", Abstract No. 66969f. *
WINDHOLZ et al., "The Merck Index", Published 1983, by MERCK & CO,, INC., (RAHWAY, N.J., U.S.A.), Tenth Edition, see pages 706 and 707, Abstract No. 4765. *

Cited By (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2757402A1 (fr) * 1996-12-24 1998-06-26 Oreal Systeme conservateur et son utilisation dans une composition cosmetique ou pharmaceutique
EP0850634A1 (fr) * 1996-12-24 1998-07-01 L'oreal Système conservateur et son utilisation dans une composition cosmétique ou pharmaceutique
US6063388A (en) * 1996-12-24 2000-05-16 L'oreal Preserving system and its use in a cosmetic or pharmaceutical composition
US5972358A (en) * 1998-01-20 1999-10-26 Ethicon, Inc. Low tack lotion, gels and creams
US5997893A (en) * 1998-01-20 1999-12-07 Ethicon, Inc. Alcohol based anti-microbial compositions with cosmetic appearance
US6022551A (en) * 1998-01-20 2000-02-08 Ethicon, Inc. Antimicrobial composition
US6080416A (en) * 1998-01-20 2000-06-27 Ethicon, Inc. Low tack lotion, gels and creams
US6248343B1 (en) 1998-01-20 2001-06-19 Ethicon, Inc. Therapeutic antimicrobial compositions
EP1080715A2 (fr) * 1999-08-05 2001-03-07 Bode Chemie GmbH & Co. Combinaison de principes actifs et compositions pour le soin des pieds le contenant
EP1080715A3 (fr) * 1999-08-05 2002-04-10 Bode Chemie GmbH & Co. Combinaison de principes actifs et compositions pour le soin des pieds le contenant
EP1769678A2 (fr) * 2001-03-01 2007-04-04 Lonza, Inc. Mélanges conservateurs contenant des composés d'ammonium quaternaire
WO2002069710A1 (fr) * 2001-03-01 2002-09-12 Lonza, Inc. Melanges conservateurs contenant des composes ammomium quaternaires
EP1769678A3 (fr) * 2001-03-01 2007-05-16 Lonza, Inc. Mélanges conservateurs contenant des composés d'ammonium quaternaire
US7342044B2 (en) 2001-03-01 2008-03-11 Lonza Inc. Preservative blends containing quaternary ammonium compounds
WO2004000373A1 (fr) * 2002-06-22 2003-12-31 Ecolab Inc. Concentre aqueux pour la desinfection de surfaces
US7160846B2 (en) 2002-06-22 2007-01-09 Ecolab Inc. Aqueous concentrate for the disinfection of surfaces
ES2323827A1 (es) * 2004-04-07 2009-07-24 Advanced Medical Optics, Inc. Cloruro de cetilpiridinio como agente antimicrobiano en composiciones oftalmicas.
WO2005097960A1 (fr) * 2004-04-07 2005-10-20 Advanced Medical Optics, Inc. Chlorure de cetylpyridinium utilise en tant qu'agent antimicrobien dans des compositions ophtalmiques
CN1942571B (zh) * 2004-04-07 2012-02-15 雅培医疗光学公司 氯化十六烷基吡啶鎓在眼药组合物中作为抗菌剂
US7578996B2 (en) 2004-04-07 2009-08-25 Advanced Medical Optics, Inc. Cetylpyridinium chloride as an antimicrobial agent in ophthalmic compositions
US8268337B2 (en) 2004-05-14 2012-09-18 Wheeler Jack A Nontoxic killer of E. coli and other problem microorganisms
WO2005112907A3 (fr) * 2004-05-14 2006-04-13 Lifetech Usa Inc Agents non toxiques permettant de detruire e. coli et d'autres micro-organismes posant des problemes
WO2005112907A2 (fr) * 2004-05-14 2005-12-01 Lifetech Usa, Inc. Agents non toxiques permettant de detruire e. coli et d'autres micro-organismes posant des problemes
WO2009047584A1 (fr) * 2007-10-11 2009-04-16 Hatchtech Pty. Ltd. Compositions de combinaison et procédés d'utilisation de celles-ci pour lutter contre une infestation
WO2016098965A1 (fr) * 2014-12-15 2016-06-23 코오롱생명과학 주식회사 Composition antiseptique et son utilisation
US11406103B2 (en) 2016-03-01 2022-08-09 Ecolab Usa Inc. Sanitizing rinse based on quat-anionic surfactant synergy
CN106119028A (zh) * 2016-07-05 2016-11-16 吴俊娟 一种三黄芎参酒
US11044907B2 (en) 2016-08-11 2021-06-29 Ecolab Usa Inc. Interaction between antimicrobial quaternary compounds and anionic surfactants
US11839209B2 (en) 2016-08-11 2023-12-12 Ecolab Usa Inc. Interaction between antimicrobial quaternary compounds and anionic surfactants
EP3496540A4 (fr) * 2016-08-11 2020-07-15 Ecolab USA Inc. Interaction entre des composés quaternaires antimicrobiens et des tensioactifs anioniques
CN110113942A (zh) * 2016-11-07 2019-08-09 朱比兰特生命科学有限公司 协同抗微生物组合物
WO2018083675A1 (fr) * 2016-11-07 2018-05-11 Jubilant Life Sciences Limited Compositions antimicrobiennes synergiques
EP3554233A4 (fr) * 2016-12-16 2020-07-22 Vertellus Holdings LLC Formulations d'amine quaternaire et leurs utilisations
CN110290703A (zh) * 2016-12-16 2019-09-27 弗特鲁斯控股有限责任公司 季胺制剂及其用途
US11825842B2 (en) 2016-12-16 2023-11-28 Aurorium Holdings Llc Quaternary amine formulations and uses thereof

Similar Documents

Publication Publication Date Title
WO1994027436A1 (fr) Conservateurs presentant une efficacite antimicrobienne amelioree
US4836986A (en) Disinfecting and preserving systems and methods of use
US4758595A (en) Disinfecting and preserving systems and methods of use
JP2554237B2 (ja) コンタクトレンズの消毒保存用溶液
JP4856392B2 (ja) 防腐剤及びこれを含有する水性組成物
CA1236752A (fr) Composes et methode de desinfection
TWI498122B (zh) 含有硼酸鹽－多元醇複合物之水性藥學組成物
KR101738502B1 (ko) 보레이트-폴리올 복합체를 함유하는 수성 약학 조성물
KR20060135006A (ko) 아연 보존제 조성물 및 사용 방법
CN101678140A (zh) 用于隐形眼镜护理和防腐的药用组合物的磷脂组合物
CA2663817A1 (fr) Compositions pharmaceutiques aqueuses a conservation spontanee
EP0053451A2 (fr) Solution(polymérique) pour la désinfection et la conservation de lentilles de contact
WO2008052031A2 (fr) Dérivés de 2-pyrrolidone pour la conservation des compositions ophtalmiques, auriculaires et nasales
US4421665A (en) Contact lens cleaning composition containing lipid solvent and method of using
JP3407654B2 (ja) 眼科用組成物
JP4725699B2 (ja) 眼科用組成物及び眼科用組成物配合用防腐剤
JPH08133911A (ja) 抗菌組成物
WO2007088783A1 (fr) Collyre pour porteurs de verres de contact souples
JP2002316926A (ja) コンタクトレンズ用眼科用組成物及び眼刺激性の緩和方法
WO2005123148A1 (fr) Composition pour lentille de contact
JP5584336B2 (ja) 防腐剤及びこれを含有する水性組成物
NZ229706A (en) Ophthalmic solution containing dodecyl-dimethyl-(2-phenoxyethyl)-ammonium bromide as an antimicrobial agent; use in cleaning, disinfecting and conditioning contact lenses
JP5713034B2 (ja) 眼科用組成物、及び眼科製剤用防腐組成物
JP4524538B2 (ja) 眼科用組成物
MXPA99005481A (en) Use of low molecular weight amino alcohols in ophthalmic compositions

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): CA JP

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: CA