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WO1996006603A1 - Agents antibacteriens contenant un compose ammonium quaternaire renfermant un poly(oxyde d'alkylene) - Google Patents

Agents antibacteriens contenant un compose ammonium quaternaire renfermant un poly(oxyde d'alkylene) Download PDF

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Publication number
WO1996006603A1
WO1996006603A1 PCT/US1995/009724 US9509724W WO9606603A1 WO 1996006603 A1 WO1996006603 A1 WO 1996006603A1 US 9509724 W US9509724 W US 9509724W WO 9606603 A1 WO9606603 A1 WO 9606603A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
alkyl
substituted
formulation
aromatics
Prior art date
Application number
PCT/US1995/009724
Other languages
English (en)
Inventor
Joonsup Park
Joseph J. Falcetta
Original Assignee
Alcon Laboratories, Inc.
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 Alcon Laboratories, Inc. filed Critical Alcon Laboratories, Inc.
Priority to AU31551/95A priority Critical patent/AU3155195A/en
Publication of WO1996006603A1 publication Critical patent/WO1996006603A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/48—Medical, disinfecting agents, disinfecting, antibacterial, germicidal or antimicrobial compositions
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C217/06—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted
    • C07C217/08—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to an acyclic carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C233/00—Carboxylic acid amides
    • C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C233/16—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
    • C07C233/17—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
    • C07C233/18—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D1/00—Detergent compositions based essentially on surface-active compounds; Use of these compounds as a detergent
    • C11D1/38—Cationic compounds
    • C11D1/62—Quaternary ammonium compounds
    • C—CHEMISTRY; METALLURGY
    • C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/0005—Other compounding ingredients characterised by their effect
    • C11D3/0078—Compositions for cleaning contact lenses, spectacles or lenses

Definitions

  • This invention is directed to ophthalmic compositions comprising quaternary ammonium compounds containing a polyalkylene oxide moiety. Some of the compounds are new. These polymeric compounds are useful as antimicrobial agents. The invention is also directed to exact molecular weight quaternary ammonium compounds containing a polyalkylene oxide moiety.
  • the antimicrobial activity of quaternary ammonium compounds is known; see for example, Petrocci, et al., Dev. Ind. Micro., 20, Chapter 1 (1978); Petrocci, Disinfection, Sterilization aid Preservation, Third Edition, Chapter 14 (1983); Hugo, et al., Principles and Practices of Disinfection, Preservation and Sterilizotion, Chapter 2 (1982).
  • U.S. Patent No. 4,567,302 and EP 214,850 disclose quaternary ammonium compounds which contain polyalkylene oxide units; however, neither disclose the compounds of the present invention.
  • U. S. Patent No. 4,110,263 discloses biquatemary ammonium compounds useful in cleansing compositions in combination with a detergent. The compounds are useful for shampoos, skin cleansers, baby and bubble baths.
  • WO 91/09522 discloses ophthalmic compositions useful in the care of contact lenses. The compositions contain a quaternary ammonium substituted matrix material selected from proteinaceous materials, carbohydrate materials, or mixtures thereof. Unlike the compounds used in the present invention, the quaternary ammonium groups are
  • EP 0153 435 A1 discloses hair care compositions containing diquatemary nitrogen polyethylene glycol derivatives.
  • CA 110(3), 23322K discloses the preparation of certain pentane diammonium debiomides as antimicrobial agents.
  • Polymeric disinfectants in general, have shown weak antifungal activity although they exhibit remarkable antimicrobial activity against other organisms.
  • This invention discloses the use of particular polymeric disinfecting agents which have a broad spectrum of antimicrobial activity, including antifungal activity. Summary of the Invention This invention is directed to contact lens care formulations and ophthalmic formulations comprising certain quaternary ammonium compounds containing a polyalkylene oxide moiety.
  • the compounds are antimicrobials and are useful as disinfecting agents and preservatives.
  • the invention is also directed to methods for using the compounds to disinfect contact lenses and preserve contact lens care solutions and ophthalmic formulations.
  • Detailed Description of Preferred Embodiments The ophthalmic formulations of this invention contain quaternary ammonium compounds containing a polyalkylene oxide moiety of the following
  • R 2 and R 3 are the same, or different, and are selected from the group: C 1 -C 20 alkyl, benzyl and substituted benzyls, aromatics and substituted aromatics and cycloalkyl and substituted cycloalkyls;
  • Q and E are the same, or different, and are selected from the group: H, C 1 -C 20 alkyl, C 2 -C 6 alkene, benzyl and substituted benzyls, aromatics and substituted aromatics, cycloalkyl and substituted cycloalkyls; heteroatom containing long alkyl chain, silane and siloxane; but, either Q and/or E must contain an alkyl structure of at least a C 5 alkyl, but not more than a C 20 alkyl moiety;
  • Z has the following structure:
  • R and R' are different and can be H, methyl or ethyl
  • n 1-4
  • Preferred compounds within the above defined structure have the following formulas:
  • the compounds are formulated into disinfecting and storage solutions for all types of contact lenses.
  • the formulations can also be used as preserved saline solutions for rinsing and as an in the eye drop to rehydrate a lens and/or to soothe the eye.
  • the compounds are also useful as preservatives in ophthalmic formulations other than lens care solutions, such as, ophthalmic pharmaceutical formulations.
  • the compounds are present in the formulations at concentrations of about 0.0001 to 1.0 weight percent (wt. %), preferably 0.0001 to 0.1 wt. %, and most preferably about 0.0005 to 0.01 wt. %
  • the compositions may contain other ingredients known to those skilled in the art of contact lens care solutions and/or ophthalmic pharmaceutical formulations.
  • the compounds of the present invention overcome some problems associated with prior antimicrobial compounds, such as benzalkonium chloride (BAC). Specifically, the use of BAC has the potential for inducing a toxic response, particularly after long term use. Without intending to be bound by any theory it is believed that the polyalkylene oxide moieties of the quaternary ammonium compounds of the present invention are responsible for the compounds producing a relatively low toxic response in ophthalmic applications. It is also believed that the polyalkylene moieties decrease the interaction of the quaternary ammonium group of the compounds with other compounds of the ophthalmic formulations or the environment to which the ophthalmic formulation is applied.
  • BAC benzalkonium chloride
  • the electron donor properties of the polyalkylene oxide moiety interact with the quaternary ammonium group (an electron acceptor group) thereby decreasing the interaction of the quaternary ammonium group with other compounds.
  • the polyalkylene oxide containing polymers have been used to reduce the interaction of polymers with biomaterials. The following data shows that the above compounds are active even in the presence of the sodium salt of polystyrene sulfonate while marked reduction in antimicrobial activity was observed from BAC under the same experimental conditions.
  • the above formulations also contain the sodium salt of polystyrene sulfonate.
  • Two general schemes were employed to synthesize the compounds of the present invention.
  • the monoquat compounds [A] were prepared starting from an aromatic substituted polyethylene oxide. An excellent starting compound was found to be p - nonylphenol polyethylene oxide. This compound was obtained as surfonic N-120 and N- 60.
  • the SURFONIC ® N series of compounds, available from Texaco, are reaction products or adducts of nonylphenol and ethylene oxides. This was reacted with thionyl chloride and then converted to a tertiary amine and then the quaternary ammonium compound according to the following general scheme.
  • diquat compounds such as [B] and [C] were prepared starting with hydroxy terminated polyalkylene oxides in the following general scheme of reactions.
  • the degree of polymerization is an expression of the number of structural units in a given polymer molecule. This number actually represents the average degree of polymerization as all the molecules will not have the same n.
  • This invention is also directed to the use of polymers with an exact molecular weight, that is, no distribution of molecular weight. New procedures for making the exact molecular weight polymers are set forth below.
  • octaethylene glycol was synthesized by following the procedure reported in J. Org. Chem., 57, 6678, (1992) (Erik M. D. Keegstra, et al.): trityl chloride was reacted with excess diethylene glycol to make a monotritylated diethylene glycol intermediate (yield: 87%) followed by reaction of two equivalents of the monotritylated compound with one equivalent of tetraethylene glycol di-p -tosylate to form the ditritylated octaethylene glycol intermediate (yield: 95%) which was then converted to octaethylene glycol by hydro genolysis with hydrogen and palladium on charcoal catalyst (purity: 97.2%, by GC yield: 90%).

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Wood Science & Technology (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention concerne des compositions ophtalmiques de composés ammonium quaternaire contenant un groupe poly(oxyde d'alkylène), utiles comme agents antibactériens. On décrit également des procédés pour utiliser ces compositions. En outre, on décrit des polymères sans répartition du poids moléculaire.
PCT/US1995/009724 1994-08-26 1995-08-02 Agents antibacteriens contenant un compose ammonium quaternaire renfermant un poly(oxyde d'alkylene) WO1996006603A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU31551/95A AU3155195A (en) 1994-08-26 1995-08-02 Polyalkylene oxide containing quaternary ammonium antimicrobial agents

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US29664094A 1994-08-26 1994-08-26
US08/296,640 1994-08-26

Publications (1)

Publication Number Publication Date
WO1996006603A1 true WO1996006603A1 (fr) 1996-03-07

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1995/009724 WO1996006603A1 (fr) 1994-08-26 1995-08-02 Agents antibacteriens contenant un compose ammonium quaternaire renfermant un poly(oxyde d'alkylene)

Country Status (2)

Country Link
AU (1) AU3155195A (fr)
WO (1) WO1996006603A1 (fr)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000007634A1 (fr) * 1998-08-06 2000-02-17 Ndt, Inc. Lentilles de contact et solutions ophtalmiques
WO2002064715A3 (fr) * 2001-02-13 2002-10-03 Bausch & Lomb Procede et solution de nettoyage et de desinfection a concentration elevee en osmolytes pour verres de contact
JP2004345953A (ja) * 2003-01-16 2004-12-09 Hiroki Koma 抗菌活性を有する新規な第四級アンモニウム塩化合物およびその製造方法
WO2010128270A3 (fr) * 2009-05-08 2011-03-31 Halliburton Energy Services, Inc. Fluides de traitement servant à réduire des blocs formés par l'eau, l'huile et/ou des condensats gazeux, et procédés associés
US8093352B2 (en) 2008-08-05 2012-01-10 Alcon Research, Ltd. Polyalkylene oxide polyquaternary ammonium biocides
US8669212B2 (en) 2009-09-03 2014-03-11 Halliburton Energy Services, Inc. Fluorosurfactants and treatment fluids for reduction of water blocks, oil blocks, and/or gas condensates and associated methods
US9308264B2 (en) 2000-11-08 2016-04-12 Fxs Ventures, Llc Ophthalmic contact lens solutions containing forms of vitamin B
US9492582B2 (en) 2000-11-08 2016-11-15 Fxs Ventures, Llc Ophthalmic and contact lens solutions containing simple saccharides as preservative enhancers
US9492581B2 (en) 2000-11-08 2016-11-15 Fxs Ventures, Llc Ophthalmic and contact lens solutions containing simple saccharides as preservative enhancers

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4110263A (en) * 1977-06-17 1978-08-29 Johnson & Johnson Baby Products Company Mild cleansing compositions containing alkyleneoxylated bisquaternary ammonium compounds
US4567302A (en) * 1984-07-20 1986-01-28 Angus Chemical Polymeric quaternary ammonium salts possessing antimicrobial activity and methods for preparation and use thereof
WO1991009522A1 (fr) * 1990-01-05 1991-07-11 Allergan, Inc. Compositions ophtalmiques et leurs procedes de conservation et d'utilisation
US5242684A (en) * 1991-10-25 1993-09-07 Isp Investments Inc. Antimicrobial, low toxicity, non-irritating composition comprising a blend of bis-quaternary ammonium compounds coprecipitated with a copolymer of vinylpyrrolidone and an acrylamido or vinyl quaternary ammonium monomer

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4110263A (en) * 1977-06-17 1978-08-29 Johnson & Johnson Baby Products Company Mild cleansing compositions containing alkyleneoxylated bisquaternary ammonium compounds
US4567302A (en) * 1984-07-20 1986-01-28 Angus Chemical Polymeric quaternary ammonium salts possessing antimicrobial activity and methods for preparation and use thereof
WO1991009522A1 (fr) * 1990-01-05 1991-07-11 Allergan, Inc. Compositions ophtalmiques et leurs procedes de conservation et d'utilisation
US5242684A (en) * 1991-10-25 1993-09-07 Isp Investments Inc. Antimicrobial, low toxicity, non-irritating composition comprising a blend of bis-quaternary ammonium compounds coprecipitated with a copolymer of vinylpyrrolidone and an acrylamido or vinyl quaternary ammonium monomer

Cited By (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1336415A3 (fr) * 1998-08-06 2004-07-28 NDT, Inc. Lentilles de contact et solutions ophtalmiques
WO2000007634A1 (fr) * 1998-08-06 2000-02-17 Ndt, Inc. Lentilles de contact et solutions ophtalmiques
US6790816B2 (en) 1999-09-24 2004-09-14 Bausch & Lomb Incorporated High osmolyte cleaning and disinfection method and solution for contact lenses
US9308264B2 (en) 2000-11-08 2016-04-12 Fxs Ventures, Llc Ophthalmic contact lens solutions containing forms of vitamin B
US10595532B2 (en) 2000-11-08 2020-03-24 Fxs Ventures, Llc Ophthalmic contact lens solutions containing forms of vitamin B
US10064410B2 (en) 2000-11-08 2018-09-04 Fxs Ventures, Llc Ophthalmic contact lens solutions containing forms of vitamin B
US9585394B2 (en) 2000-11-08 2017-03-07 Fxs Ventures, Llc Ophthalmic contact lens solutions containing forms of vitamin B
US9492581B2 (en) 2000-11-08 2016-11-15 Fxs Ventures, Llc Ophthalmic and contact lens solutions containing simple saccharides as preservative enhancers
US9492582B2 (en) 2000-11-08 2016-11-15 Fxs Ventures, Llc Ophthalmic and contact lens solutions containing simple saccharides as preservative enhancers
WO2002064715A3 (fr) * 2001-02-13 2002-10-03 Bausch & Lomb Procede et solution de nettoyage et de desinfection a concentration elevee en osmolytes pour verres de contact
JP2004345953A (ja) * 2003-01-16 2004-12-09 Hiroki Koma 抗菌活性を有する新規な第四級アンモニウム塩化合物およびその製造方法
US8093352B2 (en) 2008-08-05 2012-01-10 Alcon Research, Ltd. Polyalkylene oxide polyquaternary ammonium biocides
US8101556B2 (en) 2009-05-08 2012-01-24 Halliburton Energy Services, Inc. Treatment fluids for reduction of water blocks, oil blocks, and/or gas condensates and associated methods
WO2010128270A3 (fr) * 2009-05-08 2011-03-31 Halliburton Energy Services, Inc. Fluides de traitement servant à réduire des blocs formés par l'eau, l'huile et/ou des condensats gazeux, et procédés associés
US8772204B2 (en) 2009-09-03 2014-07-08 Halliburton Energy Services, Inc. Fluorosurfactants and treatment fluids for reduction of water blocks, oil blocks, and/or gas condensates and associated methods
US8669212B2 (en) 2009-09-03 2014-03-11 Halliburton Energy Services, Inc. Fluorosurfactants and treatment fluids for reduction of water blocks, oil blocks, and/or gas condensates and associated methods

Also Published As

Publication number Publication date
AU3155195A (en) 1996-03-22

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