US3917850A - Biocidal synergistic compositions for surface and space disinfection - Google Patents

Biocidal synergistic compositions for surface and space disinfection Download PDF

Info

Publication number
US3917850A
US3917850A US367124A US36712473A US3917850A US 3917850 A US3917850 A US 3917850A US 367124 A US367124 A US 367124A US 36712473 A US36712473 A US 36712473A US 3917850 A US3917850 A US 3917850A
Authority
US
United States
Prior art keywords
composition
phenol
biocidal
pentanedial
weight
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.)
Expired - Lifetime
Application number
US367124A
Inventor
Raymond Marcel Gut Boucher
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.)
Wave Energy Systems Inc
Original Assignee
Wave Energy Systems 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 Wave Energy Systems Inc filed Critical Wave Energy Systems Inc
Priority to US367124A priority Critical patent/US3917850A/en
Application granted granted Critical
Publication of US3917850A publication Critical patent/US3917850A/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C11ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
    • C11DDETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
    • C11D3/00Other compounding ingredients of detergent compositions covered in group C11D1/00
    • C11D3/48Medical, disinfecting agents, disinfecting, antibacterial, germicidal or antimicrobial compositions
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01NPRESERVATION 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
    • A01N35/00Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical
    • A01N35/02Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having two bonds to hetero atoms with at the most one bond to halogen, e.g. aldehyde radical containing aliphatically bound aldehyde or keto groups, or thio analogues thereof; Derivatives thereof, e.g. acetals

Definitions

  • a new biocidal composition for surface and space disinfection comprising, an aldehyde and/or dialdehyde, and a phenol derivative in ,a solvent.
  • an anionic surface active agent is added to the composition.
  • the phenol derivative can be substituted or unsubstituted and homologs thereof of phenols, quinolinols and naphthols and their salts used alone or in mixtures.
  • the anionic surface active agent can be from the family of alkyl aryl sulfonates or diphenyl oxide sulfonates.
  • the solvent can be water, benzyl alcohol alkanol or mixtures thereof. Said composition is capable of being sprayed or used in an aerosol composition.
  • the present invention contemplates novel and unique biocidal compositions for surface and space disinfection which are fast acting, stable, having a long shelf life and capable of acting over a wide temperature and pH range. They are capable of being used as sprays or as aerosols released from pressurized containers. These new biocidal compositions can be usedeither for surface disinfection of medical, dental or surgical instruments and household objects or for space disinfection as aerosol cleanser-disinfectants.
  • Another object of the present invention is to provide a new biocidal composition which can be used either for surface disinfection of medical, dental and surgical instruments and household objects or for space disinfection as aerosol cleanser-disinfectants.
  • Yet another object of the present invention is to provide a new synergistic biocidal composition for surface and space disinfection which acts swiftly at room temperature to kill a wide spectrum of microorganisms such as gram positive and gram negative bacteria, vegetative cells, fungii, viroids, viruses and most bacterial spores.
  • a further object of the present invention is to provide a new disinfectant composition comprising an aldehyde or dialdehyde with phenol derivatives, exhibiting a biolethal effect when the chemicals are dissolved in either water or alcohol solutions which may or may not contain inert fluorocarbons.
  • -A still further object: of the .present invention is to show that the hereabove. described ternary biocidal 9 with the cell wall physical damage action of phenol derivatives. This action can be further enhanced by adding small quantities of fast penetrating anionic surface active agents.
  • dialdehydes or aldehydes which have been found to be effective are those having from 1 to 8 carbon atoms, among which are methanal, ethanedial, propanedial, butanedial pentanedial, hexanedial, heptanedial and octanedial.
  • the phenol or phenol derivatives which can be used in the formulation can have one or several phenol functions and can be simple phenol homologs, bis-hydroxyphenyl alkanes, halogenated phenol derivatives, di or tri hydric phenols, nitrophenols, amino phenols, quinolinols, naphthols, etc.
  • Derivatives which have proved effective are ortho phenyl phenol, paranitrophenol, 2 chloro-4 phenyl phenol, o-benzyl p-chlorophenol, ptertiary amylphenol, 2,5 dinitrophenol, chlora-ophenylphenol, 8 quinolinol, 8 quinolinol citrate, 8- quinolino sulfate and o-phenyl phenol sodium salt.
  • the anionic surface active agents which can be used to enhance the penetration of the formulation are alkyl aryl sulfonates and diphenyl oxide sulfonates.
  • the solvent is water, benzyl alcohol, alkanol or mixtures of these.
  • compositions which will kill at room temperature a wide spectrum of microorganisms including gram positive and gram negative bacteria, vegetative cells, fungii, viroids, viruses and most bacterial spores. These compositions exhibit biolethal effects over a wide pH and temperature range in concentrations of from 0.03% to 50% by weight when dissolved in water and/or alcohol. They are effective in a pH range of from 2 to 10 and a temperature range of from 20C to C. They are also capable of being mixed with a propellant for incorporation in an aerosol.
  • the composition can be a binary or ternary composition.
  • the binary composition comprises the synergistic effect of the combination of from 0.05% to 3% by weight of the composition including solvent and propellant, if there be propellant present, of an aldehyde or dialdehyde with from 0.005% to 3% by weight of the composition including solvent and propellant, if there be propellant present, of a phenol.
  • the ternary composition adds to the binary composition of from 0.03% to about 2% by weight of the composition including solvent and propellant, if there be propellant present, of an anionic surface active agent.
  • the aldehydes or dialdehydes fround to be effective are those having 1 to 8 carbon atoms among which are methanal,
  • the phenol and phenol derivatives are phenyl phenol, paranitrophenol, 2 chloro-4 phenyl phenol, O-benzyl p-chlorophenol, p-tertiary amylphenol, 2,5 dinitrophenol, chloro-o-phenylphenol, 8-quinolinol, 8- quinolinol citrate, 8-quinolinol sulfate and o-phenyl phenol sodium salt.
  • the anionic surface active agents which are used to enhance the penetration of the formulation are: alkyl aryl sulfonates and diphenyl oxide sulfonates.
  • Two preferred anionic surface active agents are sodium dodecyl diphenyl ether disulfonate and sodium n-decyl diphenyl ether disulfonate both in liquid form in a concentration of 45%.
  • Dowfax 382 registered tradename of Dow Chemical for a sodium salt of a C alpha olefin of a diphenyl ether disulfonate
  • Dowfax 2A1 registered tradename of Dow Chemical for a sodium salt of a dodecylated diphenyl ether disulfonate.
  • Both compounds contain mono and dialkylated species in a ratio of about 80% to mono-to diand both products are completely sulfonated. These are used in a liquid form having a 45% concentration.
  • the solvent can be water benzyl alcohol or a low molecular weight alkanol or a combination of one or more of the above.
  • the low molecular weight alkanol can be methyl alcohol, ethyl alcohol, isopropyl alcohol or normal propyl alcohol.
  • a liqified or compressed gas propellant such as isobutane, propane, freon, chlorofluoroalkanes, ethane, carbon dioxide, nitrous oxide or nitrogen can be used with the above composition.
  • the solvent or solvent-propellant mixture is present in the composition in an amount of from about 50% to 99.9% by weight of the total weight of the entire composition, including the biocidal solution.
  • the polymers formed in the acid range are of the acetal-like structure and they can revert to the monomer by heating thus explaining the high biocidal activity disclosed in G. Sierras patent (U. S. Pat. No. 3,697,222).
  • the polymers formed in the alkaline range are of a different chemical structure and cannot be reverted to the monomer by heating thus explaining the short biocidal life of alkaline glutaraldehyde solutions.
  • tuberculosis which often resists the action of pentanedial.
  • T. Bergan and A. Lystad have shown, for instance, (J. Appl Bact., 1971) that under Kelsey-Sykes procedure 2% alkaline pentanedial is not tuberculocidal.
  • the phenol derivatives used in the formula of the invention modify the microorganisms protective membrane to such an extent that they facilitate the penetration of aldehyde/dialdehydes thus promoting a faster 6
  • other substances may be added to the novel compositions of the present invention provided they have no detrimental effects on the biocidal activity of the compositions. Examples of such subkilling rate. This has been observed even with hard to 5 stances would be perfumes, odor masking chemicals, penetrate bacterial spores having multilayered coats dyes, pH indicators, anti-corrosion agents, inert fluorocontaining disulphide rich proteins. It has also been obcarbons for aerosolization and the like.
  • Table I illustrates five typical compositions of the in- 'agents successfully boosted the lethal effect of our new vention which are called A, B, C, D and E. These comcmposition while other non-ionic agents reduced or positions will later be referred to as(A:100 or 8:100, completely destroyed the antimicrobial action of our etc.) when used at a 1: 100 dilution with water or any phenol formulation. In most of our experiments synother suitable solvent mixture.
  • composition Composition Composition Compgsition Components in Components in Components in Components in Components in weight weight weight weight weight weight Pentanedial 2.5 Ethanedial l Pentanedial 3 Pentanedial 1.5 Pentanedial 2.5
  • Exposure time 10 minutes at 20C.
  • composition A 10 minutes at 20C Active chemicals means: dialdehyde phenol derivatives anionic agents.
  • aureus a high biocidal activity at pH 3 when using phenols activated with anionic agents.
  • 2-4-5 trichlorophenol shows a phenol coefficient of 40 when tested at pH 6 against S. typhosa'but at pH 10 or higher the phenol coefficient drops to about 1.
  • the tests were of the use dilution type and they were performed according to the procedure described in the AOAC Methods, 1 lthe Edition, 1970.
  • the stainless 9 steel carriers, free from surface defects, were prepared and sterilized according to the directions.
  • the 48-54 hours cultures of the various bacteria were grown in nutrient broth, prepared as directed in 4.001A with Anatone. These were used to contaminate the cylinders in the manner prescribed.
  • the cultures were examined for resistance to Phenol at 20C in each case as directed.
  • the resistance to phenol was found to exceed the maximum requirements of the test. As the culture resistance to phenol exceeded the maximum requirements as to concentration and contact time, each culture used was checked to show that it was resistant to phenol in the highest concentration required, and for the maximum time (15' minutes).
  • the apparatus used for these experiments consisted of an insulated tank equipped with cooling coils and a Heto heating and circulating pump. This enabled the temperature to be controlled to 101C.
  • One contaminated carrier was added to 10 cc of composition A at 30 second intervals. Following the contact period the cylinder was subcultured into 10 cc of sterile fluid Thioglycolate media and shaken. The tubes were then incubated at 37C for 48hours and examined for growth.
  • Composition B shown in Table I is such an example of a formulation with biocidal synergism extended in the alkaline range.
  • the S-Quinolinol derivatives have no toxicityand both the citrate and sulfate do not decrease the biocidal synergism when added to acid solution of pentanedial or other compatible saturated dialdehydes.
  • biocidal compositions within the framework of the present invention can be used to formulate biocidal compositions within the framework of the present invention; however, the biocidal effect is dependent not only upon the dialdehyde mo
  • the spori'cidal or biocidal activity of the various dialdehydes seem to follow the same general trend as their solubility in water.
  • the biocidal activity decreases when the length of the --CH chain increases (i.e. when the distance between the two aldehyde radicals increases).
  • a maximum of biocidal activity is observed with three CI-I between the two aldehydes. It is to be noted that according to S. D. Rubbo et al. (J. Appl. Bact.
  • aldehydes to be used in the synergistic formulation are mainly methanal, ethanedial, propanedial, butanedial, pentanedial, and hexaneo'ial for aqueous solutions.
  • formulating alcoholic solutions for aerosol sprays one could add to the above-mentioned list heptanedial and octanedial.
  • compositions F and G are two examples of such a formulation for use in alkaline pH range.
  • Table XII 15 shows the biocidal effect produced by the combination of phenol derivatives with pentanedial with and without an anionic surfactant in an alkaline formulation.
  • composition C Composition C (See Table I) (without phenol) (without aldehyde) Salmonella clmleraesuis 0/30 0/30 +/30 Staphylococcus aureus O/30 0/30 0/30 Streptococcus Pyogener 0/30 0/30 +/3O Trichoplzyton interdigitale 0/30 +/3O +l30 0 denotes no growth in 30 tests denotes growth in 30 tests "As described in the AOAC. 10th Ed.. 1965, p.
  • phenol or phenol derivatives to be used in the present invention can have one or several phenol functions (i.e. free hydroxyl group) and be simple phenol homologs, bis-I-Iydroxyphenyl alkanes, halogenated phenol derivatives, di or tri hydric phe- TABLE XII Synergistic Mycobactericidal effect of Formula F AOAC Test Procedure* Formula F Formula F Formula F without phenols without dialdehydes (see Table XI) Culture Media Pos Neg** Pos Neg Pos Neg Proskauer and Beck with and without serum 10 6 24 0 30 Dubos Broth with serum 24 6 3 27 0 30 *10 minute exposure to biocidal solution at 20C (30 test tubes).
  • biocidal synergistic formulations of the present invention are single phase liquid compositions, they can be used undiluted or diluted (see Table III) on surfaces or sprayed in aerosol form (see composition B and D, Table I). Upon discharge from aerosol pressurized cans, they will produce either coarse wet sprays or fine dry aerosol mists according to the type of valve and according to the physical characteristics of the propellant gas. As previously shown in Tables IX and X, the highly potent biocidal compositions will exhibit a 100% kill both as surface and space aerosol disinfectants. They will also leave a continuous thin film on sprayed surfaces which will remain a sufficient time to disinfect but will not be thick enough to cause spotting.
  • the single phase solvent-propellant mixture may approximately correspond to the following composition by weight:
  • alcohol such as methyl alcohol, ethyl alcohol, isopropyl alcohol or benzyl alcohol, from 5 to 70% of total weight composition.
  • a liquified or compressed gas propellant such as isobutane, propane, Freon, chlorofluoromethane and ethane, carbon dioxide, nitrous oxide, nitrogen, etc.
  • the propellant may appropriately be present in a quantity of about 2 to 25% by weight of the total formulation.
  • the relative amounts of said water, alcohol and propellant in the solvent system are such that said composition has a vapor pressure of from to pounds per square inch gauged at 70F.
  • a comparison between the two formula in the alkaline range confirms the fact that a saturated dialdehyde with 7 carbons is less biocidal than the 3 or 4 carbons type.
  • the 8- Quinolinol citrate is more active than a higher concentration of 8-Quinolinol sulfate.
  • the ratio of water to alcohol can vary widely without affecting the biocidal activity of our compositions as long as the active agents are completely soluble in the proper amount in the solvent system.
  • compositions of the present invention contrary to pentanedial solu-' tions, are stable over long periods of time even when stored continuously at temperatures as high as 60C.
  • Table XIV the compositions of the present invention retain their biocidal activity after high temperature storage both in the acid and alkaline pH range. This is an important feature from the practical view point since in the past it greatly limited all applications with pentanedial solutions.
  • biocidal activity of the formulations described in Stonehills US. Pat. No. 3,282,775 were said to be only 2 weeks when stored at room temperature.
  • compositions are capable of being used in either a liquid form or as a spray.
  • a disinfectant composition consisting essentially of pentanedial 2.5% by weight, para nitro phenol 1.6% by weight, O-phenyl phenol 0.1% by weight, sodium n- Biocidal activity of solutions stored at 60C.
  • Microorganism Trichophyton Mentagrophytes ATCC 9533.
  • AOAC Test Procedure 1 1th Ed., 1970 pl-l one month two months three months twelve months Alkaline glutaraldehyde (2%) 8 Composition C with bufier 3.3 Composition F 8.5 Composition G 8.5

Abstract

A new biocidal composition for surface and space disinfection comprising, an aldehyde and/or dialdehyde, and a phenol derivative in a solvent. In a preferred embodiment, an anionic surface active agent is added to the composition. The phenol derivative can be substituted or unsubstituted and homologs thereof of phenols, quinolinols and naphthols and their salts used alone or in mixtures. The anionic surface active agent can be from the family of alkyl aryl sulfonates or diphenyl oxide sulfonates. The solvent can be water, benzyl alcohol alkanol or mixtures thereof. Said composition is capable of being sprayed or used in an aerosol composition.

Description

United States Patent [1 1 Boucher Nov. 4, 1975 BIOCIDAL SYNERGISTIC COMPOSITIONS FOR SURFACE AND SPACE DISINFECTION [75] Inventor: Raymond Marcel Gut Boucher, New
[21] Appl. No.: 367,124
[52] US. Cl. 424/333; 424/346; 424/348 [51] Int. (11. AOlN 9/24; AOlN 9/00; AOlN 9/26 [58] Field of Search 424/333, 45, 258, 346, 1 424/348 [56] References Cited UNITED STATES PATENTS 7 3,016,328 1/1952 Pepper et al 424/333 3,057,775 10/1962 Rendon 424/75 3,282,775 1 H1966 Stonehill 424/333 3,697,222 10/1972 Sierra 424/333 FOREIGN PATENTS OR APPLICATIONS 874,713 7/1971 Canada OTHER PUBLICATIONS N.J., pp. 545, 804 and 1060-1061, (1960). McCutcheons, Detergents to Emulsifiers, 1971 annul, Allured Publ. Corp., Ridgewood, N.J., pp. 47-48, (1971).
Chemistry of the Pesticides, D. Frear, C0. Van Nostrand Co., lnc., New York, pp. 290-292, 1955.
Primary Examiner-Albert T. Meyers Assistant Examiner-Douglas W. Robinson Attorney, Agent, or FirmShoemaker and Mattare 57 ABSTRACT A new biocidal composition for surface and space disinfection comprising, an aldehyde and/or dialdehyde, and a phenol derivative in ,a solvent. In a preferred embodiment, an anionic surface active agent is added to the composition. The phenol derivative can be substituted or unsubstituted and homologs thereof of phenols, quinolinols and naphthols and their salts used alone or in mixtures. The anionic surface active agent can be from the family of alkyl aryl sulfonates or diphenyl oxide sulfonates. The solvent can be water, benzyl alcohol alkanol or mixtures thereof. Said composition is capable of being sprayed or used in an aerosol composition.
1 Claim, No Drawings BIOCIDAL SYNERGISTIC COMPOSITIONS FOR SURFACE ANDSPACE DISINFECTION BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention contemplates novel and unique biocidal compositions for surface and space disinfection which are fast acting, stable, having a long shelf life and capable of acting over a wide temperature and pH range. They are capable of being used as sprays or as aerosols released from pressurized containers. These new biocidal compositions can be usedeither for surface disinfection of medical, dental or surgical instruments and household objects or for space disinfection as aerosol cleanser-disinfectants.
2. Description of the Prior Art It has long been known that low concentrations of saturated dialdehydes such as pentanedial in the alkaline pH range (R. E. Pepper et al., US. Pat. No. 3,016,328), and in the neutral or acid pH range (G. Sierra, US. Pat. No. 3,697,222) display increasing biocidal activity under the influence of various external agents such as heat as shown in G. Sierra, Canadian Pat. No. 865,913, cationic compounds as shown in A. A. Stonehill, US. Pat. No. 3,282,775, anionic and non ionic additives as set forth in R. M. G. Boucher, US. Patent application Ser. No. 155,233 or ultrasonics as taught by G. Sierra, Canadian Pat. No. 874,713.
SUMMARY OF THE INVENTION It is accordingly one object of the present invention to provide a new biocidal composition for surface and space disinfection which is stable having a long shelf life and capable of acting effectively over a wide range of temperatures and pH.
Another object of the present invention is to provide a new biocidal composition which can be used either for surface disinfection of medical, dental and surgical instruments and household objects or for space disinfection as aerosol cleanser-disinfectants.
Yet another object of the present invention is to provide a new synergistic biocidal composition for surface and space disinfection which acts swiftly at room temperature to kill a wide spectrum of microorganisms such as gram positive and gram negative bacteria, vegetative cells, fungii, viroids, viruses and most bacterial spores.
A further object of the present invention is to provide a new disinfectant composition comprising an aldehyde or dialdehyde with phenol derivatives, exhibiting a biolethal effect when the chemicals are dissolved in either water or alcohol solutions which may or may not contain inert fluorocarbons.
' It is also a further object of the present invention to show that specific compatible mixtures in the proper ratio of saturated aldehydes or dialdehydes with phenol derivatives and anionic agents can exhibit a biolethal effect especially in a pH range equal to or lower than 7, over a wide-temperature range (20C to 100C), over an extended scale of dilution (50% chemicals concentrate down to 0.03%) when the chemicals are dissolved either in water or in an alcoholic solution which may or i may not contain inertfluorocarbons.
-A still further object: of the .present invention is to show that the hereabove. described ternary biocidal 9 with the cell wall physical damage action of phenol derivatives. This action can be further enhanced by adding small quantities of fast penetrating anionic surface active agents.
The dialdehydes or aldehydes which have been found to be effective are those having from 1 to 8 carbon atoms, among which are methanal, ethanedial, propanedial, butanedial pentanedial, hexanedial, heptanedial and octanedial.
The phenol or phenol derivatives which can be used in the formulation can have one or several phenol functions and can be simple phenol homologs, bis-hydroxyphenyl alkanes, halogenated phenol derivatives, di or tri hydric phenols, nitrophenols, amino phenols, quinolinols, naphthols, etc. Derivatives which have proved effective are ortho phenyl phenol, paranitrophenol, 2 chloro-4 phenyl phenol, o-benzyl p-chlorophenol, ptertiary amylphenol, 2,5 dinitrophenol, chlora-ophenylphenol, 8 quinolinol, 8 quinolinol citrate, 8- quinolino sulfate and o-phenyl phenol sodium salt.
The anionic surface active agents which can be used to enhance the penetration of the formulation are alkyl aryl sulfonates and diphenyl oxide sulfonates.
The solvent is water, benzyl alcohol, alkanol or mixtures of these.
DESCRIPTION OF THE PREFERRED EMBODIMENTS In accordance with the present invention, there has been found new disinfectant compositions which will kill at room temperature a wide spectrum of microorganisms including gram positive and gram negative bacteria, vegetative cells, fungii, viroids, viruses and most bacterial spores. These compositions exhibit biolethal effects over a wide pH and temperature range in concentrations of from 0.03% to 50% by weight when dissolved in water and/or alcohol. They are effective in a pH range of from 2 to 10 and a temperature range of from 20C to C. They are also capable of being mixed with a propellant for incorporation in an aerosol.
As stated above, the composition can be a binary or ternary composition. The binary composition comprises the synergistic effect of the combination of from 0.05% to 3% by weight of the composition including solvent and propellant, if there be propellant present, of an aldehyde or dialdehyde with from 0.005% to 3% by weight of the composition including solvent and propellant, if there be propellant present, of a phenol. The ternary composition adds to the binary composition of from 0.03% to about 2% by weight of the composition including solvent and propellant, if there be propellant present, of an anionic surface active agent. The aldehydes or dialdehydes fround to be effective are those having 1 to 8 carbon atoms among which are methanal,
ethanedial, propanedial, butanedial pentanedial, hex-' anedial, heptanedial and octanedial. The aldehyde most preferred, which will be seen from the following tests is pentanedial (glutaraldehyde).
The phenol and phenol derivatives are phenyl phenol, paranitrophenol, 2 chloro-4 phenyl phenol, O-benzyl p-chlorophenol, p-tertiary amylphenol, 2,5 dinitrophenol, chloro-o-phenylphenol, 8-quinolinol, 8- quinolinol citrate, 8-quinolinol sulfate and o-phenyl phenol sodium salt.
With regard to the ternary composition, the anionic surface active agents which are used to enhance the penetration of the formulation are: alkyl aryl sulfonates and diphenyl oxide sulfonates. Two preferred anionic surface active agents are sodium dodecyl diphenyl ether disulfonate and sodium n-decyl diphenyl ether disulfonate both in liquid form in a concentration of 45%. Some specific examples of these compounds are Dowfax 382 registered tradename of Dow Chemical for a sodium salt of a C alpha olefin of a diphenyl ether disulfonate and Dowfax 2A1 registered tradename of Dow Chemical for a sodium salt of a dodecylated diphenyl ether disulfonate. Both compounds contain mono and dialkylated species in a ratio of about 80% to mono-to diand both products are completely sulfonated. These are used in a liquid form having a 45% concentration.
The solvent can be water benzyl alcohol or a low molecular weight alkanol or a combination of one or more of the above. The low molecular weight alkanol can be methyl alcohol, ethyl alcohol, isopropyl alcohol or normal propyl alcohol.
When used as an aerosol, a liqified or compressed gas propellant such as isobutane, propane, freon, chlorofluoroalkanes, ethane, carbon dioxide, nitrous oxide or nitrogen can be used with the above composition.
The solvent or solvent-propellant mixture is present in the composition in an amount of from about 50% to 99.9% by weight of the total weight of the entire composition, including the biocidal solution.
To aid in the understanding of the biocidal synergistic effects of the three different types of chemicals used in the formulation of the present invention, hereinafter are reviewed the main bio-physical and bio-chemical mechanisms which take place at molecular level with each type of chemical used in the novel formulation.
At the moment it is believed that saturated dialdehydes such as ethanedial, propanedial, butanedial or pentanedial produce aldehyde-amino reactions with cell proteins (R. M. G. Boucher et al, Proc. West. Pharm. 800., Lake Tahoe, January, 1973). The chemical sites for saturated dialdehyde action could therefore involve NH groups, including cross linking reactions between these groups (D. Hopwood, Histochemie; 17-151, 1968), although this does not exclude sites of action with other chemical groups (sulfhydryl, hydroxyl, carboxy, etc.). It has been well established that aldehydes (and this is particularly true for methanal and pentanedial) have a tendency to form polymers. In the case of pentanedial (A. A. Stonehill et al, Am. Journ. Hosp. Pharm., September, 1963) this chemical loses its biocidal activity when it undergoes polymerization. The rate of polymerization increases with the pH and this limits the use of alkaline pentanedial to two weeks when the solution is buffered between 7.5 and 8.5. Above pH 9 the polymerization is extremely fast and this dialdehyde becomes useless as a biocidal agent.
To avoid aldehydes/dialdehydes polymerization new compositions in the acid range have been recently suggested (R. M. G. Boucher, Am. Journ. Hosp. Pharm., August, 1972). Studies conducted with a 220 MHz pro- 4 ton .li'uclear Magentic Resonance Spectrometer at the Ontario Research Foundation and in England (P. M. Hardy, et al., chem. Comm. 1969) have shown that in the case of pentanedial the monomer (suspected to be the only biocidal agent) is constantly in equilibrium with various types of polymers. The polymers formed in the acid range are of the acetal-like structure and they can revert to the monomer by heating thus explaining the high biocidal activity disclosed in G. Sierras patent (U. S. Pat. No. 3,697,222). The polymers formed in the alkaline range are of a different chemical structure and cannot be reverted to the monomer by heating thus explaining the short biocidal life of alkaline glutaraldehyde solutions.
It has also been recently shown (T. J. Munton et al., J. Appl. Bact., 1972) that at room temperature initial uptake of glutaraldehyde by E. Coli cells are the same in the acid and alkaline range. However, under alkaline conditions the outer layers of the cell are damaged to a greater extent. This could explain why at room temperature alkaline glutaraldehyde is more sporicidal than acid glutaraldehyde. The reverse being true when the temperature rises. When the external protective layer of a microorganism is difficult to penetrate or to combine with, the biocidal effect of the aldehydes/dialdehydes decreases. This is the case, for instance, of the waxy lipo proteins layer of M. tuberculosis which often resists the action of pentanedial. Recent studies by T. Bergan and A. Lystad have shown, for instance, (J. Appl Bact., 1971) that under Kelsey-Sykes procedure 2% alkaline pentanedial is not tuberculocidal.
To improve the biocidal action of dialdehydes the addition of certain surface active agents (R. M. G. Boucher, U.S. Pat. application Ser. No. 155,233), heat (G. Sierra, U.S. Pat. No. 3,697,222) or ultrasonics (G. Sierra, Can. Pat. No. 874,713) have already been suggested. Combining both phenolic derivatives and aldehydes or dialdehydes with or without anionic detergents is the object of the invention, and we shall show that it provides unsurpassed results for destroying the toughest Mycobacteria at room temperature even when the bacilli are coated with mucous or necrotic caseous substance. This is indeed understandable if one remembers that fast penetration of the aldehyde radicals through cell walls is the key to strong biocidal action. The bactericidal action of phenol depends upon its rendering the cell wall permeable to certain essential cell constituents. This was, for instance, clearly demonstrated by E. F. Gale and E. S. Taylor (J. Gen. Microb., 1947) who found that in the case of Streptococcus faecalis a 1% solution of phenol caused a leak of glutamic acid almost as intensive as produced by boiling. That phenol causes leakage of essential metabolites from the cell was also confirmed by measuring the release of radioactivity from E. Coli grown on various labeled compounds (J. Judis, Journ. Pharm. Sci., 1963). The biocidal mechanism of phenol agents is not restricted to cell membrane alteration and as well known, it can also affect bacterial enzymes involved in metabolic phenomena. This has been clearly demonstrated by D. Bach and J. Lambert (J. Am. Pharm. Assoc., 1937). Studies of these authors on certain dehydrogenases of Staphylococcus aureus showed that a 1:1000 dilution of phenol acting for 30 minutesdestroyed the systemsactivating succinate, fumarate, pyruvate and glutamate while the lactate, glucose, formate and butanol systems experienced partial inactivation.
The phenol derivatives used in the formula of the invention modify the microorganisms protective membrane to such an extent that they facilitate the penetration of aldehyde/dialdehydes thus promoting a faster 6 It is obvious that other substances may be added to the novel compositions of the present invention provided they have no detrimental effects on the biocidal activity of the compositions. Examples of such subkilling rate. This has been observed even with hard to 5 stances would be perfumes, odor masking chemicals, penetrate bacterial spores having multilayered coats dyes, pH indicators, anti-corrosion agents, inert fluorocontaining disulphide rich proteins. It has also been obcarbons for aerosolization and the like. served with the thick cortex layer containing murein in Having described the modus operandi of the three bacterial spores. main classes of chemicals used to observe synergistic To further accelerate the diffusion of aldehydel- 10 biocidal effects, the following examples and tests will dialdehydes into the core of protoplast of microorganfurther illustrate the invention. They are given primarisms we successfully added to the aldehyde-dialily for the purpose of illustration and should not be condehydes/phenol derivative composition small amounts strued as limiting the invention to the details given. of synthetic detergents of the anionic type. These Table I illustrates five typical compositions of the in- 'agents successfully boosted the lethal effect of our new vention which are called A, B, C, D and E. These comcmposition while other non-ionic agents reduced or positions will later be referred to as(A:100 or 8:100, completely destroyed the antimicrobial action of our etc.) when used at a 1: 100 dilution with water or any phenol formulation. In most of our experiments synother suitable solvent mixture.
TABLE I Composition Composition Composition Composition Compgsition Components in Components in Components in Components in Components in weight weight weight weight weight Pentanedial 2.5 Ethanedial l Pentanedial 3 Pentanedial 1.5 Pentanedial 2.5
Para nitro Methanal l 8-Quinolinol 0.5 S-Hydroxyquino- 8-Hydroxyquinophenol 1.6 line citrate 1.5 line sulfate 2.5
O-phenyl phenol 0.1 2,4,5, 2
trichlorophenol Sodium n-decyl diphenyl ether disulfonate 45% concentration in Sodium n-decyl diphenyl ether disulfonate 45% concentration in Sodium dodecyl diphenyl ether disulfonate 45% concentration in Sodium dodecyl diphenyl ether disulfonate 45% concentration in liquid form liquid form liquid form liquid form (DOWFAX 3B2)* 0.25 (DOWFAX 3B2)* 0.25 (DOWFAX 2A1)* 0.5 DOWFAX 2Al* 2 Fragrance Fragrance Fragrance 0.1 Fragrance or Fragrance or (essential 011) 0.1 (essential oil) 0.1 deodorant 0.2 deodorant 0.1 Soft water 95.45 lsopropyl 46.9 Water 96.4 Benzyl alcohol 67 Water 92.9
alcohol Fluorocarbon Propellant (propellant) 28.65 (Fluorocarbon) Water 20.1 Water 9.3 Alkalinating (if Agent needed) Trademark of Dow Chemical Co.
thetic cationic agents such as those mentioned in A. A. To assess the synergistic, effect of the Formulation A, Stonehills patent (U. 5. Pat. No. 3,282,775) interfered for instance; Mywacleriytm tuberculosis was Chosen with the phenol additive and destabilized the biocidal F F ms 9 made P P i gamsm is more resistant to chemical inactivation Composmon' than other vegetative bacteria. The procedure followed was the official method of the Association of Official Of Special interest were the synthetic anionic detergf x g g g g Pi 3 ou t e 0 101a me o c s or ten test tu es, ig: 2321: 22 g ggfi gggi eF-i gi thirty were used in all the experiments. Four different h culture media were used which are all described in s all be shown are stable in the acid pH range and they JAOAC (4 04543 4048 a (2) (4) and (5) Tubes Increase the blo-cldal activity the aldehyde-dial were incubated at 37C foi' days then examined for dehyde/phenol mixture. Sa1d chemicals at a concentrawth Wh Its doubtf 1 Smears were tion as low as 0.03% in weight are particularly efficient 60 gm ere were u in the 2 to 5 pH range. They also greatly improve liquid clarity and tolerance of the biocidal mixture to hard water. It has also been found that the above mentioned synthetic detergents do not adversely affect the aldehyde-dialdehydes/polymer equilibrium in the neutral and acid pH range.
made from the centrifuged sediment, strained by the Z.N. method and examined microscopically for acid fast bacilli.
All these tests reported in Table II were conducted at a temperature of 20C with a constant exposure time of 10 minutes.
TABLE 11 Tests conducted with Composition A (see Table 1).
Exposure time: 10 minutes at 20C.
Chemical Agents P* (2.5%) An (0.25%) FL (1.7%) P+An P+PL P+An+PL PL+An Culture Media Pos. Neg" Pos Neg Pos Neg Pos Neg Pos Neg Pos Neg Pos Neg Proskauer and Beck with and without serum 20 10 30 19 l1 l5 l5 8 22 0 30 20 10 Middlebrook's 7H9 Broth l9 ll 30 0 22 8 14 16 10 20 0 30 21 9 Dubos Broth with serum 24 6 30 0 14 16 10 20 3 27 0 30 15 15 TB Broth Base without Polysorbate 80 30 0 30 0 5 25 20 10 4 26 0 10 20 P. An and PL mean pentanedial, anionic agent and phenol derivatives. respectively.
"Negative means no growth (i.e. the microorganism has been killed).
TABLE III Composition A (see Table I) 10 minutes at 20C Active chemicals means: dialdehyde phenol derivatives anionic agents.
Dilution of Active Chemicals Composition A Concentration Pos. Neg. l 4.45% (weight) 0 30 1:10 0.44 0 30 1:50 0.08 l 29 1:100 0.04 26 4 1:1000 0.004 30 0 Composition C (see Table l) 15 minutes at 20C Dilution of Active Chemicals Composition C Concentration Pos. Neg. l 3.5% 0 30 1:10 0.35 0 30 1:50 0.07 0 30 1:100 0.03 0 30 1:1000 0.003 30 0 Composition E (see Table I) 10 minutes at 20C Dilution of Active Chemicals Composition E Concentration Pos. Neg. l 7% 0 30 1:10 0.7 0 30 1:50 0.14 0 30 1:100 0.07 18 12 1:1000 0.007 30 0 As previously explained, any increase of temperature will favor the reaction of the pentanedial monomer with cell proteins; and it is also known that Mycobacteria are very sensitive to temperature. It is, therefore, obvious that raises in temperature will only increase the synergistic mycobactericidal effect. This is clearly shown in Table IV.
Phenol TABLE IV-continued Tests on a stock culture of BCG (Exposure time 5 minutes) *All tests conducted with a ten minute exposure corresponded to no growth (i.e. 30 neg) Trademark of Dow Chemical Co.
Regarding the influence of pH on the compositions of the present invention, there are two important facts. As previously stated, commercial pentanedial solutions (50 or 25% concentrate) have a pH comprised between 2 and 5. In this range they are already highly bactericidal (this includes pseudomonocidal) due to the presence of a large amount of monomers in equilibrium with reversible monomers. G. Sierra and R. M. G. Boucher (J. Appl. Microb., August, 1971) have shown that the biocidal activity of aqueous acid pentanedial solutions tested with wet naked spores of B. subtilis (ATCC 6051) is independent of the pH below 7. It is only in the alkaline range between 7.5 and 8.5 that a surge in biocidal activity (of limited duration in time) is observed before the biocidal action sharply decreases (near pH 9). It is therefore obvious that operating in the acid range will not create a problem with the chosen saturated clialdehydes. Phenols and phenol derivatives are stable in the acid range and generally speaking, the addition of alkali decreases their germicidal action until a dence (E. J. Ordal et al., J. Bact., 1942). The effect of pH is particularly noticeable when phenols are solubilized wth alkyl aryl sulfonates. M. Rosein et al. (Farmacia, 1960) have shown with S. aureus a high biocidal activity at pH 3 when using phenols activated with anionic agents. To use an example, 2-4-5 trichlorophenol shows a phenol coefficient of 40 when tested at pH 6 against S. typhosa'but at pH 10 or higher the phenol coefficient drops to about 1.
This explains why the formulations of the present invention are very effective in the acid range, especially between 2 and 3. 8. All the mechanisms involved in the synergistic biocidal effect hereabove described point to a strong microbiocidal action below pH 7. In table V there is shown a series of results obtained with composition A and C which confirm the theoretical considerations.
The tests were of the use dilution type and they were performed according to the procedure described in the AOAC Methods, 1 lthe Edition, 1970. The stainless 9 steel carriers, free from surface defects, were prepared and sterilized according to the directions. The 48-54 hours cultures of the various bacteria were grown in nutrient broth, prepared as directed in 4.001A with Anatone. These were used to contaminate the cylinders in the manner prescribed. The cultures were examined for resistance to Phenol at 20C in each case as directed. The resistance to phenol was found to exceed the maximum requirements of the test. As the culture resistance to phenol exceeded the maximum requirements as to concentration and contact time, each culture used was checked to show that it was resistant to phenol in the highest concentration required, and for the maximum time (15' minutes).
The apparatus used for these experiments consisted of an insulated tank equipped with cooling coils and a Heto heating and circulating pump. This enabled the temperature to be controlled to 101C. One contaminated carrier was added to 10 cc of composition A at 30 second intervals. Following the contact period the cylinder was subcultured into 10 cc of sterile fluid Thioglycolate media and shaken. The tubes were then incubated at 37C for 48hours and examined for growth.
TABLE V Influence Phenol Resistance line range by a proper choice of chemicals. Composition B shown in Table I is such an example of a formulation with biocidal synergism extended in the alkaline range.
Although conversion of phenol and of the phenol derivatives to the corresponding sodium or potassium phenates causes a reduction in bactericidal power, the phenates are far more soluble than the corresponding phenols. Phenates may also act as solubilizers for the phenols. Thus by increasing the soluble amount of biocidal agents, one compensates for the decreased effectiveness of the phenates. This indeed is well known and explains the wide use of alkaline phenol salt germicidal formulations. One key novelty of the present invention was the discovery that within certain limits of pH (between 7 and 9) mixtures of alkaline phenols do retard the irreversible polymerization of saturated dialdehydes such as pentanedial and ethanedial. In other words, an alkaline pentanedial solution (pl-l 7 to 9) which normally will start to lose its potency after 2 weeks will retain'it after 1 month when mixed with an anionic agent and phenol deravitives. This important observation makes it also possible to prepare highly potent room temperature tuberculocidal formulations with a longer life than those described in US. Pat. Nos. 3,016,328 and 3,282,775. It also enables decreasing Organism. P Cone min min min time for fast mycobactericidal action on highly resisps tant strains. Table VI and VII provide pertinent data gf fgg g which clearly establishes the biocidal synergism of the 15442 2 o 39 compositions of the present invention in the alkaline 2.6 0 1:80 range.
TABLE VI Aging Tests M. Tuberculosis Test AOAC Sporicidal Test (AOAC at 20C) Temperature 60C 20 minutes Solution B. subtilis CI. sporogenes Formulation Age Pos. Neg. Rings Loops Rings Loops Composition A 2 weeks 0 30 0/30 0/30 0/30 7 0/30 (adjusted to pH 8*) 4 weeks 0 30 0/30 0/30 0/30 0/30 7 months 0/30 0/30 0/30 0/30 Alkaline pentanedial 2 weeks l 29 0/30 0/30 0/30 0/30 (2% sol, pH 8) 4 weeks 8 22 0/30 l/30 0/30 3/30 i 7 months 2/30 8/30 3/30 l5/30 With buffering agents 3.7 0 39' 1:80- v t I v4.7 0 .39- 1:80 I It 1s 1n the acid range (especially between a pH of 2 2g {528' I to 3.8) that the compositions of the instant invention V L 1 are particularlyefficient from the biocidal view point. nuance 9* P P SY F B Q C The choice of the proper phenol derivatives is impor- (10 minute exposure) 1 1 tant in the acid range due to the relatively poor SOlllbllor anism H i f v 5 zg 'li fi f g ity of phenols in water. One of the phenol derivatives g p f 4 which was successfully used in the instant formulations was the para nitro phenol whose solubility in 100 gr of chaleraesuls o (ATCC water at 25 C is close to 1.6 gr. Another phenol derlva- 10708) 2 p 0 g 1 38: I I tive which gave excellent results is 8-Hydroxyquinoline if; 8 2 E or S-Quinolinol which is soluble in aqueous mineral 4.7 0 33 1:90 acids. Since the solubility of this chemical is rather g? 3 :38 I i 1 poor innon acidified water there was used with great success the 8-Hydroxyquinoline citrate which is freely pH adjusted with buffers Table V clearly shows that the synergistical biocidal soluble in water. Also of interest was the S-Hydroxyquinoline sulfate which is soluble in water but is diffi-- cult to use in aerosol formulation due to its relatively.
poor solubility in alcohol. The S-Quinolinol derivatives have no toxicityand both the citrate and sulfate do not decrease the biocidal synergism when added to acid solution of pentanedial or other compatible saturated dialdehydes.
12 lecular shape but also its solubility in the solvent used for the formulation.
TABLE VIII CORRESPONDING SOLUBILI'IY IN SPORICIDAU TYPE or ACID ALDEHYDE WATER AT 20C ACTIVITY H-COOH HCHO Methanal FORM IC (Formaldehyde) SOL GOOD HOOC-COOl-I CIHO Ethanedial OXALIC cno (Glyoxal) SOL GOOD cno HOOCCH2COOH cu. Propanedial MALONIC cno (Malonaldehyde) SOL SL. ACTIVE /cno HOC(CH C0OH(c Butanedial SUCCINIC CI-IO (Succinaldehyde) SOL SL. ACTIVE /CHO nooc cl-i,).,coov ci-i Pemanedlal GLUTARIC \CHO (Glutaraldehyde) s01. EXCELLENT /CHO noocqcmncoorrcmy, l'lexanedlal ADIPIC CHO (Adipaldehyde) SL. SOL. SL. ACTIVE HOOC cu cooixcfi $1. $01. v POOR 2 5 2 5 HMEUC \CHO l-leptanedral HOOC-(CH COOH 2)6 Octanedial NOT SOL V- POOR SUBERIC CH0 References to Sporicidal Activity Deal with tests on B. Anthracis, Cl. TETANI, Cl. SPOROGENES. B SUBTILIS and B. PUMILUS IN AQUEOUS AND ALCOHOLIC SOLUTIONS. The names which are not between parenthesis have been approved by the International Union of Chemistry TABLE VII AOAC Tuberculocidal test with varying exposure times at C Note no growth growth It has been established (S. D. Rubbo, et al., J. Appl. Bact., 1967) that the biocidal effect of saturated dialdehydes is related to the presence of two free reactive aldehyde groups. It is, therefore, obvious that dialdehydes such as propanedial, hexanedial, butanedial, pentanedial, heptanedial, octanedial, etc. can be used to formulate biocidal compositions within the framework of the present invention; however, the biocidal effect is dependent not only upon the dialdehyde mo As can be seen in Table VIII, the spori'cidal or biocidal activity of the various dialdehydes seem to follow the same general trend as their solubility in water. As a general but not absolute rule, the biocidal activity decreases when the length of the --CH chain increases (i.e. when the distance between the two aldehyde radicals increases). A maximum of biocidal activity is observed with three CI-I between the two aldehydes. It is to be noted that according to S. D. Rubbo et al. (J. Appl. Bact. 30:1, 78-87, 1967) the presence of two aldehyde groups is a must to observe any biocidal activity. This has been established in a series of tests shown in Table IX comparing the biocidal activity of valeraldehyde (pentanal, CH (CI-I -Cl -IO) with pentanedial (CI-IO (CH -CHO) in alcoholic solutions. It has also been shown by S. D. Rubbo et al. that substitution in the molecule without alteration of the aldehyde group, as in the methyl derivative of pen tanedial, reduces the rate of kill but does not eliminate the biocidal activity. Water base formulation sometimes may not allow increasing the dialdehyde concentration up to the level necessary for fast action. In such cases, the difficulty could be avoided through the use of lower alkanol solvents such as methanol, ethyl alcohol, or isopropyl alcohol.
TABLE IX Aerosol Germicidal Testing Composition D TABLE IX-continued Aerosol Germicidal Testing* Composition D replacing Composition D Pentanedial by (See Table I) Valeraldehyde Trichoplzylon inlerdigitale /30 +/30 To illustrate the importance of the choice of the dialdehyde, S. Rubbo et al. showed that at a pH 8 the time required to inactivate B. anthracis by a factor of was minutes with pentanedial while little effect was observed with propanedial, all other experimental conditions being equal. In short, from the data presented in Table VIII one can see that the aldehydes to be used in the synergistic formulation are mainly methanal, ethanedial, propanedial, butanedial, pentanedial, and hexaneo'ial for aqueous solutions. When formulating alcoholic solutions for aerosol sprays, one could add to the above-mentioned list heptanedial and octanedial.
To further show the effect of the binary composition used as an aerosol, the following tests were made as 14 nols, nitrophenols amino phenols, Quinolinols, naphthols, etc. Phenol derivatives choice will be guided, mainly for acid range formulation, by the solubility of these compounds in water or dialdehyde solutions. In some cases it will be advisable to increase the amount of dissolved phenols by adding a certain proportion of alcohols. For the formulations in the alkaline range, it is recommended to use a slight excess in alkali to form the corresponding phenate which acts as solubilizer.
10 The presence of the anionic agents, diphenyl oxide sulfonates or alkyl aryl sulfonates will also help to adjust phenol concentration at the proper level. Compositions F and G, given in Table XI, are two examples of such a formulation for use in alkaline pH range. Table XII 15 shows the biocidal effect produced by the combination of phenol derivatives with pentanedial with and without an anionic surfactant in an alkaline formulation.
Sodium salt of 2 chloro 4-phenyl phenol (Dowcide 4) 4% 4% O-phenyl phenol, sodium salt. Tetrahydrate- (Dowcide A) 5% 5% Anionic agent (Dowfax 3B2) 2% none pI-I adjusted between 8 10 Inert ingredients (water,
fragrance, corrosion inhibitor,
shown in Table X. etc-l 77% TABLE X Aerosol Germicidal Testing* Composition C Composition C Composition C (See Table I) (without phenol) (without aldehyde) Salmonella clmleraesuis 0/30 0/30 +/30 Staphylococcus aureus O/30 0/30 0/30 Streptococcus Pyogener 0/30 0/30 +/3O Trichoplzyton interdigitale 0/30 +/3O +l30 0 denotes no growth in 30 tests denotes growth in 30 tests "As described in the AOAC. 10th Ed.. 1965, p. 89, Gerrnicidal Spray Products", the spray was applied to the test surfaces by holding the container 8 inches away and spraying for 5 seconds. Letheen broth subculture medium was used with staphylococcus aureus, salmonella choleraesuis and Sabouraud letheen broth with Trichophyton interdigitale. Trypticase Soy Broth with 10% serum was used with streptococcus pyogenes (beta-hemolytic type A).
Regarding the phenol or phenol derivatives to be used in the present invention, they can have one or several phenol functions (i.e. free hydroxyl group) and be simple phenol homologs, bis-I-Iydroxyphenyl alkanes, halogenated phenol derivatives, di or tri hydric phe- TABLE XII Synergistic Mycobactericidal effect of Formula F AOAC Test Procedure* Formula F Formula F Formula F without phenols without dialdehydes (see Table XI) Culture Media Pos Neg** Pos Neg Pos Neg Proskauer and Beck with and without serum 10 6 24 0 30 Dubos Broth with serum 24 6 3 27 0 30 *10 minute exposure to biocidal solution at 20C (30 test tubes). **Negative means no growth. Synergistic Mycobactericidal effect of Formula G AOAC Test Procedure*** Formula G Formula G Formula G without phenols without dialdehydes (see Table XI) Culture Media Pos Neg Pos Neg Pos Neg Proskauer and Beck with and without serum 22 8 8 22 0 30 Dubos Browth with serum 23 7 5 25 0 ***l5 minute exposure to biocidal solution at 20C (30 test tubes).
Because the biocidal synergistic formulations of the present invention are single phase liquid compositions, they can be used undiluted or diluted (see Table III) on surfaces or sprayed in aerosol form (see composition B and D, Table I). Upon discharge from aerosol pressurized cans, they will produce either coarse wet sprays or fine dry aerosol mists according to the type of valve and according to the physical characteristics of the propellant gas. As previously shown in Tables IX and X, the highly potent biocidal compositions will exhibit a 100% kill both as surface and space aerosol disinfectants. They will also leave a continuous thin film on sprayed surfaces which will remain a sufficient time to disinfect but will not be thick enough to cause spotting.
While not a critical feature of the present invention, best results are achieved when the essential ingredients of the aerosol formulation of the present invention are used in the following approximate proportions by weight:
From 0.05% to about 7% based on the weight of the composition of active material said active material being:
a. from 20 to 45% of an aldehyde or saturated dialdehydes.
b. from 15 to 45% of phenol derivatives.
c. from to of anionic surfactants (when present).
The single phase solvent-propellant mixture may approximately correspond to the following composition by weight:
0. water, from 20 to 83% of total weight composition.
d. alcohol such as methyl alcohol, ethyl alcohol, isopropyl alcohol or benzyl alcohol, from 5 to 70% of total weight composition.
e. a liquified or compressed gas propellant such as isobutane, propane, Freon, chlorofluoromethane and ethane, carbon dioxide, nitrous oxide, nitrogen, etc. The propellant may appropriately be present in a quantity of about 2 to 25% by weight of the total formulation. As a general rule, well known to the man of the art, the relative amounts of said water, alcohol and propellant in the solvent system are such that said composition has a vapor pressure of from to pounds per square inch gauged at 70F.
Several typical aerosol formulations which correspond to the teachings of the invention are shown in Table XIII.
A comparison between the two formula in the alkaline range confirms the fact that a saturated dialdehyde with 7 carbons is less biocidal than the 3 or 4 carbons type. In the acid range, one can see that the 8- Quinolinol citrate is more active than a higher concentration of 8-Quinolinol sulfate. One can also see that the ratio of water to alcohol can vary widely without affecting the biocidal activity of our compositions as long as the active agents are completely soluble in the proper amount in the solvent system.
TABLE XIII DISINFECTANT FORMULA FOR SYNERGISTIC AEROSOL MIXTURES Active Agents Ethyl Freon* Active Agents O-phenyl phenol Na salt 2.5 Heptanedial Pentanedial 8 Quinolinol Dowfax 2A1 8 Quinolinol Dowfax 332 7.5 65 lsopropyl Ethyl 20 Freon l0 Freon l l 0.5
Pentanedial 8-Quinolinol Citrate Dowfax 2Al Dialdehydes Phenols or Phenol derivative Anionic Agent Solvent System Water Alcohol Propellant Inert Ingredients (including buffer) Aerosol Germicidal Efficiencv( See analytical procedure in Table IX) pH of composition lsopropyl A-46 gas "Dichlorodifluoromethane "A mixture of about 87% isobutane and 13% propane, by volume, manufactured by Phillips.
It is also important to note that the compositions of the present invention, contrary to pentanedial solu-' tions, are stable over long periods of time even when stored continuously at temperatures as high as 60C. As can be seen in Table XIV, the compositions of the present invention retain their biocidal activity after high temperature storage both in the acid and alkaline pH range. This is an important feature from the practical view point since in the past it greatly limited all applications with pentanedial solutions. As previously mentioned, the biocidal activity of the formulations described in Stonehills US. Pat. No. 3,282,775, were said to be only 2 weeks when stored at room temperature.
TABLE XIV room temperature over a wide pH. The compositions are capable of being used in either a liquid form or as a spray.
Having thus described the compositions of the invention in terms of their preferred embodiments as set forth in the descriptions and examples of the aforesaid specification, it is apparent to those skilled in the art that various changes and modifications can be made in these compositions without departing from the spirit and scope of the invention.
What is claimed is:
1. A disinfectant composition consisting essentially of pentanedial 2.5% by weight, para nitro phenol 1.6% by weight, O-phenyl phenol 0.1% by weight, sodium n- Biocidal activity of solutions stored at 60C. Microorganism: Trichophyton Mentagrophytes ATCC 9533. AOAC Test Procedure, 1 1th Ed., 1970 pl-l one month two months three months twelve months Alkaline glutaraldehyde (2%) 8 Composition C with bufier 3.3 Composition F 8.5 Composition G 8.5
Note: tests conducted at 20C, no growth, growth decyl diphenyl ether disulphonate 0.25% by weight and the remainder water.

Claims (1)

1. A DISINFECTANT COMPOSITION CONSISTING ESSENTIALLY OF PENTANEDIAL 2.5% BY WEIGHT, PARA NITRO PHENOL 1.6% BY WEIGHT, O-PHENYL PHENOL 0.1% BY WEIGHT, SODIUM N-DECYL DIPHENYL ETHER DISULPHONATE 0.25% BY WEIGHT AND THE REMAINDER WATER.
US367124A 1973-06-05 1973-06-05 Biocidal synergistic compositions for surface and space disinfection Expired - Lifetime US3917850A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US367124A US3917850A (en) 1973-06-05 1973-06-05 Biocidal synergistic compositions for surface and space disinfection

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US367124A US3917850A (en) 1973-06-05 1973-06-05 Biocidal synergistic compositions for surface and space disinfection

Publications (1)

Publication Number Publication Date
US3917850A true US3917850A (en) 1975-11-04

Family

ID=23446008

Family Applications (1)

Application Number Title Priority Date Filing Date
US367124A Expired - Lifetime US3917850A (en) 1973-06-05 1973-06-05 Biocidal synergistic compositions for surface and space disinfection

Country Status (1)

Country Link
US (1) US3917850A (en)

Cited By (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4103001A (en) * 1976-08-30 1978-07-25 Schattner Robert I Buffered phenol-glutaraldehyde sterilizing compositions
US4376094A (en) * 1980-08-30 1983-03-08 Sterling Drug Inc. Method of disinfecting and a method for destroying bacteria and fungi using 2-substituted glutaraldehydes
DE3144137A1 (en) * 1981-11-06 1983-05-19 Schülke & Mayr GmbH, 2000 Norderstedt Surface disinfectants
EP0255875A1 (en) * 1986-08-08 1988-02-17 Germo S.P.A. Glutaraldehyde-based sterilising composition of antibacterial and antimycotic activity in an aqueous vehicle
US4978530A (en) * 1986-05-02 1990-12-18 Health Care Products, Inc. Sanitized, disinfected and sporicidal articles, and processes for sanitizing, disinfecting and rendering objects sporicidal
WO1991000689A1 (en) * 1989-07-11 1991-01-24 Wave Energy Systems, Inc. Odorless mycobactericidal compositions
US5004757A (en) * 1988-12-20 1991-04-02 Wave Energy Systems, Inc. Virucidal low toxicity compositions
US5219890A (en) * 1989-07-11 1993-06-15 Wave Energy Systems, Inc. Odorless Mycobactericidal compositions
US5250573A (en) * 1986-08-08 1993-10-05 Germo S.P.A. Glutaraldehyde-based sterilising composition of antibacterial and antimycotic activity, in an aqueous vehicle
WO1994027437A1 (en) * 1993-05-28 1994-12-08 Bayer Aktiengesellschaft Chemical disinfectants based on phenolic active components and glutaraldehyde
US5503778A (en) * 1993-03-30 1996-04-02 Minnesota Mining And Manufacturing Company Cleaning compositions based on N-alkyl pyrrolidones having about 8 to about 12 carbon atoms in the alkyl group and corresponding methods of use
US5573710A (en) * 1993-03-30 1996-11-12 Minnesota Mining And Manufacturing Company Multisurface cleaning composition and method of use
US5622696A (en) * 1993-11-10 1997-04-22 Camiener; Gerald W. Safe dialdehydes useful as embalming agents
US5637559A (en) * 1993-03-30 1997-06-10 Minnesota Mining And Manufacturing Company Floor stripping composition and method
US5863547A (en) * 1997-02-25 1999-01-26 Healthpoint, Ltd. Glutaraldehyde plus alcohol product
US5922665A (en) * 1997-05-28 1999-07-13 Minnesota Mining And Manufacturing Company Aqueous cleaning composition including a nonionic surfactant and a very slightly water-soluble organic solvent suitable for hydrophobic soil removal
US5942217A (en) * 1997-06-09 1999-08-24 The Procter & Gamble Company Uncomplexed cyclodextrin compositions for odor control
US6043287A (en) * 1989-06-23 2000-03-28 Nakamura; Junsuke Disinfectant composition and a disinfection method using the same
US6150320A (en) * 1994-07-21 2000-11-21 3M Innovative Properties Company Concentrated cleaner compositions capable of viscosity increase upon dilution
WO2001065938A1 (en) * 2000-03-06 2001-09-13 Laboratorio Coloma Bioseguridad Ambiental, S.A. Improved bactericide applied with a doser on air conditioning conduits
US6586477B1 (en) * 2002-10-31 2003-07-01 Sporicidin Company Teat dip composition containing phenol and phenate
US20030196968A1 (en) * 2002-01-17 2003-10-23 Verichem, Inc. Synergistic mixtures of o-phenylphenol and other nitrogen and aldehyde microbiocides
US20050003994A1 (en) * 2000-12-14 2005-01-06 Dietmar Ochs Surface-active compositions
US6849589B2 (en) 2001-10-10 2005-02-01 3M Innovative Properties Company Cleaning composition
US20070010586A1 (en) * 2005-07-11 2007-01-11 Healthpoint, Ltd. Enhanced tuburculocidal activity and decreased fumes from glutaraldehyde disinfectant using acetate salts and alcohol
US20070098672A1 (en) * 2005-11-02 2007-05-03 O'sullivan Kevin W Fogger propellant system for containing and dispersing antimicrobial and air freshening compounds
US20070292465A1 (en) * 2006-06-16 2007-12-20 Clariant International, Ltd. Eutectic biocide compositions and formulations
US20080227679A1 (en) * 2007-03-13 2008-09-18 Elementis Specialties, Inc. Biodegradable Cleaning Compositions
US20100218964A1 (en) * 2009-02-27 2010-09-02 Daniel Galloway Compressed gas-driven device with passive thermodynamic composition
US8833078B2 (en) 2009-02-27 2014-09-16 D2Bg Llc Compressed gas-driven device with passive thermodynamic composition
WO2016196115A1 (en) * 2015-05-31 2016-12-08 Dow Global Technologies Llc Microbicidal composition containing glutaraldehyde and orthophenylphenol
TWI700034B (en) * 2017-12-24 2020-08-01 日商日本歐愛特農業科技股份有限公司 Synergistic bactericide composition containing nitrophenol compound and bactericidal active compound

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3016328A (en) * 1961-01-03 1962-01-09 Ethicon Inc Dialdehyde alcoholic sporicidal composition
US3057775A (en) * 1959-02-04 1962-10-09 Champion Co Embalming composition
US3282775A (en) * 1963-05-10 1966-11-01 Ethicon Inc Sporicidal compositions comprising a saturated dialdehyde and a cationic surfactant
US3697222A (en) * 1970-08-03 1972-10-10 Ontario Research Foundation Sterilization with glutaraldehyde

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3057775A (en) * 1959-02-04 1962-10-09 Champion Co Embalming composition
US3016328A (en) * 1961-01-03 1962-01-09 Ethicon Inc Dialdehyde alcoholic sporicidal composition
US3282775A (en) * 1963-05-10 1966-11-01 Ethicon Inc Sporicidal compositions comprising a saturated dialdehyde and a cationic surfactant
US3697222A (en) * 1970-08-03 1972-10-10 Ontario Research Foundation Sterilization with glutaraldehyde

Cited By (45)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4103001A (en) * 1976-08-30 1978-07-25 Schattner Robert I Buffered phenol-glutaraldehyde sterilizing compositions
US4376094A (en) * 1980-08-30 1983-03-08 Sterling Drug Inc. Method of disinfecting and a method for destroying bacteria and fungi using 2-substituted glutaraldehydes
DE3144137A1 (en) * 1981-11-06 1983-05-19 Schülke & Mayr GmbH, 2000 Norderstedt Surface disinfectants
US4978530A (en) * 1986-05-02 1990-12-18 Health Care Products, Inc. Sanitized, disinfected and sporicidal articles, and processes for sanitizing, disinfecting and rendering objects sporicidal
US5250573A (en) * 1986-08-08 1993-10-05 Germo S.P.A. Glutaraldehyde-based sterilising composition of antibacterial and antimycotic activity, in an aqueous vehicle
EP0255875A1 (en) * 1986-08-08 1988-02-17 Germo S.P.A. Glutaraldehyde-based sterilising composition of antibacterial and antimycotic activity in an aqueous vehicle
US5004757A (en) * 1988-12-20 1991-04-02 Wave Energy Systems, Inc. Virucidal low toxicity compositions
US6043287A (en) * 1989-06-23 2000-03-28 Nakamura; Junsuke Disinfectant composition and a disinfection method using the same
US5219890A (en) * 1989-07-11 1993-06-15 Wave Energy Systems, Inc. Odorless Mycobactericidal compositions
WO1991000689A1 (en) * 1989-07-11 1991-01-24 Wave Energy Systems, Inc. Odorless mycobactericidal compositions
US5744440A (en) * 1993-03-30 1998-04-28 Minnesota Mining And Manufacturing Company Hard surface cleaning compositions including a very slightly water-soluble organic solvent
US5503778A (en) * 1993-03-30 1996-04-02 Minnesota Mining And Manufacturing Company Cleaning compositions based on N-alkyl pyrrolidones having about 8 to about 12 carbon atoms in the alkyl group and corresponding methods of use
US5573710A (en) * 1993-03-30 1996-11-12 Minnesota Mining And Manufacturing Company Multisurface cleaning composition and method of use
US5637559A (en) * 1993-03-30 1997-06-10 Minnesota Mining And Manufacturing Company Floor stripping composition and method
US6008259A (en) * 1993-05-28 1999-12-28 Bayer Aktiengesellschaft Chemical disinfectants based on phenolic active components and glutaraldehyde
AU686635B2 (en) * 1993-05-28 1998-02-12 Bayer Aktiengesellschaft Chemical disinfectants based on phenolic active components and glutaraldehyde
US5696170A (en) * 1993-05-28 1997-12-09 Bayer Aktiengesellschaft Chemical disinfectant based on phenolic active components and glutaraldehyde
WO1994027437A1 (en) * 1993-05-28 1994-12-08 Bayer Aktiengesellschaft Chemical disinfectants based on phenolic active components and glutaraldehyde
US5622696A (en) * 1993-11-10 1997-04-22 Camiener; Gerald W. Safe dialdehydes useful as embalming agents
US6150320A (en) * 1994-07-21 2000-11-21 3M Innovative Properties Company Concentrated cleaner compositions capable of viscosity increase upon dilution
US5863547A (en) * 1997-02-25 1999-01-26 Healthpoint, Ltd. Glutaraldehyde plus alcohol product
US5922665A (en) * 1997-05-28 1999-07-13 Minnesota Mining And Manufacturing Company Aqueous cleaning composition including a nonionic surfactant and a very slightly water-soluble organic solvent suitable for hydrophobic soil removal
US5942217A (en) * 1997-06-09 1999-08-24 The Procter & Gamble Company Uncomplexed cyclodextrin compositions for odor control
WO2001065938A1 (en) * 2000-03-06 2001-09-13 Laboratorio Coloma Bioseguridad Ambiental, S.A. Improved bactericide applied with a doser on air conditioning conduits
ES2159269A1 (en) * 2000-03-06 2001-09-16 Coloma Bioseguridad Ambiental Improved bactericide applied with a doser on air conditioning conduits
US7041631B2 (en) * 2000-12-14 2006-05-09 Ciba Specialty Chemicals Corporation Surface-active compositions comprising a mixture of diphenyl ether and o-phenyl pheno
US20050003994A1 (en) * 2000-12-14 2005-01-06 Dietmar Ochs Surface-active compositions
US6849589B2 (en) 2001-10-10 2005-02-01 3M Innovative Properties Company Cleaning composition
US7262222B2 (en) * 2002-01-17 2007-08-28 Verichem, Inc. Synergistic mixtures of o-phenylphenol and other nitrogen and aldehyde microbiocides
US20030196968A1 (en) * 2002-01-17 2003-10-23 Verichem, Inc. Synergistic mixtures of o-phenylphenol and other nitrogen and aldehyde microbiocides
US20070203126A1 (en) * 2002-01-17 2007-08-30 Carlson Paul E Synergistic Mixtures of O-Phenylphenol and Dazomet
US6586477B1 (en) * 2002-10-31 2003-07-01 Sporicidin Company Teat dip composition containing phenol and phenate
US20070010586A1 (en) * 2005-07-11 2007-01-11 Healthpoint, Ltd. Enhanced tuburculocidal activity and decreased fumes from glutaraldehyde disinfectant using acetate salts and alcohol
US8658190B2 (en) 2005-07-11 2014-02-25 Dfb Technology, Ltd. Enhanced tuburculocidal activity and decreased fumes from glutaraldehyde disinfectant using acetate salts and alcohol
US20070098672A1 (en) * 2005-11-02 2007-05-03 O'sullivan Kevin W Fogger propellant system for containing and dispersing antimicrobial and air freshening compounds
US20070292465A1 (en) * 2006-06-16 2007-12-20 Clariant International, Ltd. Eutectic biocide compositions and formulations
US20080227679A1 (en) * 2007-03-13 2008-09-18 Elementis Specialties, Inc. Biodegradable Cleaning Compositions
US8635873B2 (en) 2009-02-27 2014-01-28 D2Bg Llc Compressed gas-driven device with passive thermodynamic composition
US20100218964A1 (en) * 2009-02-27 2010-09-02 Daniel Galloway Compressed gas-driven device with passive thermodynamic composition
US8833078B2 (en) 2009-02-27 2014-09-16 D2Bg Llc Compressed gas-driven device with passive thermodynamic composition
WO2016196115A1 (en) * 2015-05-31 2016-12-08 Dow Global Technologies Llc Microbicidal composition containing glutaraldehyde and orthophenylphenol
CN108064130A (en) * 2015-05-31 2018-05-22 陶氏环球技术有限责任公司 Synergistic microbicidal compositions containing glutaraldehyde and o-phenyl phenol
JP2018525325A (en) * 2015-05-31 2018-09-06 ダウ グローバル テクノロジーズ エルエルシー Microbicidal composition containing glutaraldehyde and orthophenylphenol
JP2021098723A (en) * 2015-05-31 2021-07-01 ダウ グローバル テクノロジーズ エルエルシー Microbicidal composition containing glutaraldehyde and orthophenylphenol
TWI700034B (en) * 2017-12-24 2020-08-01 日商日本歐愛特農業科技股份有限公司 Synergistic bactericide composition containing nitrophenol compound and bactericidal active compound

Similar Documents

Publication Publication Date Title
US3917850A (en) Biocidal synergistic compositions for surface and space disinfection
US4093744A (en) Killing bacterial spores with glutaraldehyde sporicidal compositions
US5707993A (en) Glycine anhydride dimethylol as a biocide and preservative
EP0160051B1 (en) Foamable biocide composition
US4557898A (en) Method of disinfecting and sterilizing with hydrogen peroxide compositions
JP6063495B2 (en) Alpha-ketoperacids and methods for making and using the same
US3824190A (en) Phenolic synthetic detergent-disinfectant
US4518585A (en) Hydrogen peroxide disinfecting and sterilizing compositions
US4851449A (en) Odorless aromatic dialdehyde disinfecting and sterilizing composition
JP2010526816A (en) Antibacterial composition and methods of making and using the same
JPH05271073A (en) Anti (pseudomonas aeruginosa) agent
US6525101B2 (en) Ready-to-use glutaraldehyde concentrates
BRPI0207420B1 (en) process and compositions for disinfecting alkali resistant surfaces
US4971999A (en) Odorless aromatic dialdehyde disinfecting and sterilizing composition and method of using the same
EP1369037A1 (en) Synergistic preparations based on mixtures of glycerol ether with aromatic alcohol for controlling mycobacteria
US20220015367A1 (en) Self-assembled active agents
US4173653A (en) Oxydiacetaldehyde compositions used as disinfectants
US4208404A (en) Glutaraldehyde sterilizing compositions
NO131113B (en)
EP2861567B1 (en) Antimicrobial compounds
US5674829A (en) Stable aqueous glutaraldehyde solutions containing sodium acetate and a nonionic detergent
EP0603303A1 (en) Antimicrobial compositions containing propylene carbonate and/or ethylene carbonate as the carrier solvent
Gorman et al. Potentiation and stabilization of glutaraldehyde biocidal activity utilizing surfactant-divalent cation combinations
FR2649587A1 (en) INODORATED MYCOBACTERICIDAL COMPOSITIONS
Gordon et al. Enhancement of mycobactericidal activity of glutaraldehyde with α, β-unsaturated and aromatic aldehydes