Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/40—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
  • A61K8/41—Amines
  • A61K8/416—Quaternary ammonium compounds

Definitions

• This invention relates to quaternary ammonium compounds and, more particularly, to 2-hydroxyalkyl quaternary ammonium compounds having a pronounced antiseptic character.
• antiseptic is used in its broad sense and is intended to include all bacteriological activity, including bacteriostatic and bactericidal activity.
• Quaternary ammonium compounds are Widely employed as germicidal agents due to their recognized microbial activity. They have been found to exhibit both bacteriostatic and bactericidal properties, as well as significant surface active properties. In view of these characteristics quaternary ammonium compounds have gained wide acceptance as effective agents for the sterilization of surgical and dental instruments, eating utensils, and food processing machinery and equipment.
• Quaternary ammonium compounds have been found to be particularly suited for such personal use in that they are eifective when used in solutions of moderate strength and also exhibit a prolonged bacteriostatic activity.
• Quaternary ammonium compounds may be characterized as nitrogen compounds in which four carbon atoms are directly linked to the nitrogen atom through covalent bonds and in which an anion is linked to the nitrogen atom through an electrovalent bond.
• Compounds which are illustrative of the general class of quaternary ammonium compounds include the alkenyldimethylethylammonium halides, alkenyltrimethylammonium halides, alkyldimethylbenzylamrnonium halides, alkyltrimethylammonium halides, dialkyldimethylammonium halides, and the like.
• R and R are the same or different groups such 3,369,046 Patented Feb. 13, 1968 ice as C to C alkyl groups, for example, methyl, ethyl, npropyl, isopropyl and the like, or a C to C alkanol group, such as ethanol, n-propanol, isopropanol and the like;
• R is an alkyl radical having from 6 to 18 carbon atoms, preferably from 6 to 16 carbon atoms, e.g., hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl and hexadecyl, heptadecyl, and nonadecyl;
• X is hydrogen or a halogen, such as chlorine, iodine or bromine; and Y is a halogen
• Illustrative quaternary ammonium compounds include N-propyl-N- Z-hydroxyethyl) -N- (2hydroxyoctyl -N- benzyl ammonium chloride,
• the preferred quaternary ammonium compounds are N-rnethyl-N- Z-hydroxyethyl) -N- 2-hydroxydodecyl) N-benzyl ammonium chloride and N-methyl-N- Z-hydroxyethyl) -N- 2-hydroxydodecyl) N-(p-bromobenzyl) ammonium bromide.
• novel 2-hydroxyalkyl quaternary ammonium compounds are prepared by condensing an appropriate 1,2- epoxyalkane with an equimolar amount of a suitable secondary amine to provide a tertiary amine characterized by the presence of a 2-hydroxy group on the longest alkyl radical attached to the nitrogen atom.
• the corre sponding quaternary ammonium compound is then prepared by condensing the thus prepared tertiary amine with an equimolar amount of a suitable arylalkyl halide compound, such as a benzyl halide or a p-halobenzyl halide.
• Illustrative 1,2-epoxyalkanes which can be used for the preparation of tertiary amines suitable for use in preparing the novel Z-hydroxyalkyl quaternary ammonium compounds include 1,2-epoxyoctane, l,2-epoxynonane, 1,2-epoxydecane, 1,2-epoxyundecane, 1,2-epoxydodecane, 1,2epoxytridecane, 1,2-epoxytetradecane, 1,2- epoxypentadecane, 1,2-epoxyhexadecane, and the like as well as mixtures of these compounds, e.g., mixture of epoxyalkanes containing both even and odd numbers of carbon atoms in the alkyl chain.
• Illustrative secondary amine reactants include dimethylamine, diethylamine, methylethylamine, diethanolamine, dipropanolamine, methylmonoethanolamine and the like.
• Organic halides suitable for condensation with the tertiary amines referred to above include arylalkyl halides, such as benzyl chloride, benzyl bromide, benzyl iodide; halobenzyl halides, such as p-bromobenzyl bromide, pchlorobenzyl chloride and the like.
• bacteriologically active amounts represents that amount of the particular compound which will kill or inhibit the growth of microorganisms.
• factors such as possible contact time, the nature of the micro-organisms and the conditions under which the antiseptic composition is to be used determine what constitutes a bacteriologically active amount.
• Example 1Cndensati0n of LZ-epcrxyalkanes with merhyl-monoethanolamine N methyl N (2 hydroxyethyl) 2 hydroxyalkylamines were produced by heating a reaction mixture comprising 0.5 mole of a 1,2-epoxyalkane and 0.5 mole of methyl-monoethanolamine dissolved in about 75 milliliters of ethyl alcohol on a steam bath until a homogeneous solution was obtained. The temperature was then increased and the ethyl alcohol distilled oh; the final traces of ethyl alcohol were removed at reduced pressure.
• Table I presents data on a series of N-methyl-N-(2- hydroxyethyl)-2-hydroxyalkylamines prepared as described above.
• the alkyl groups shown in the first column of Table I represent R of Formula 1, above.
• Example 3 N methyl N (2 hydroxyethyl) (2-hydroxyalkyl)- N-benzyl ammonium chlorides were prepared by refluxing equimolar quantities (0.05 mole) of a tertiary amine prepared as described in Example 1, with benzyl chloride in 30 grams of ethanol. The reaction mixture was refluxed at 50 C. for 24 hours, after which it was cooled to room temperature and stored at room temperature for 10 days. At the end of this period, the ethanol was removed and the reaction product was stored over concentrated sulfuric acid at a pressure of 200 millimeters of mercury until the product crystallized.
• Example 5 N,N-bis(2-hydroxyethyl) N (2 hydroxyalkyl) N- benzyl ammonium chlorides were prepared by refluxing together equimolar amounts (0.1 mole) of an N-(Z-hydroxyalkyl) diethanolamine prepared as described in Example 2 and benzyl chloride in 75 milliliters of npropyl alcohol for a period of 6 hours. The n-propyl alcohol was then removed by evaporation. The last traces of n-propyl alcohol were removed by heating the reaction product to 54 C. at a pressure of 30 millimeters of mercury. The resulting product was then dried over concentrated sulfuric acid at a pressure of 0.5 millimeters of mercury.
• Quaternary ammonium compounds of the type described herein have been tested for germicidal activity and have been found to possess a significant degree of such activity.
• the minimum effective concentration for representative quaternary ammonium compounds was determined by means of a gradient plate tech nique in which agar plates having a gradual proportional increase in the concentration of antiseptic compound along the gradient axis were employed. Such plates are poured with two layers of nutrient, the bottom layer consisting of plain nutrient which is allowed to harden while the plate is slanted so that a wedge-shaped layer is formed. A second nutrient layer containing the antiseptic material is then poured while the plate is fiat. Downward diffusion of the antiseptic establishes a uniform linear concentration gradient during incubation. The plates are inoculated by streaking a bacterial culture suspension across the surface of the nutrient. The plates are incubated at 37 C. overnight and the extent of bacterial growth is measured.
• the Compound agamstinitial inoculum density is calculated from quadruplicate onguclear wli loop samples taken from a control tube incubated as above which is prepared by admixing 1 milliliter of 0.1 percent gy i-( r y hy i; -lay y- 44 84 peptone water and 1 milliliter of a 10* dilution of the iii g i ffii gi gfigt itfihfiigagg r--- pooled saliva.
• the average colony count in the control ggg gzg g- -tr y ammonium 1 66 multiplied by the dilution factor represents the initial fi idl(ifini-bfiifig iji i liififi dgi inoculum density of the test mixture. Since the test mixdodecyll-N'bemyl ammonium chloride tures containing mouthwash employ undiluted saliva, any 15 count showing the same number of colonies as the con- A group of quaternary ammonium compounds containtrol represents 99.9% kill of the initial inoculum. The ing a 2-hydroxy substituent in the longest alkyl chain was time required to effect a 99.9% kill is recorded.
• aureus Saliva Bacteriostatic activity was determined by an Agar Dilution Cup test (ADC) in which a standard Petri Dish NirInEethyl-N-(2-hylroxgeglyb- Z-hydroxydo ecy was filled w1th 40 milliliters of thioglycollate agar seeded 25 bemyl ammonium chloride M2 1p 4 3 at 1 percent with a culture of S. aureus. After hardening, 0. 05 3.5 2.7 M a cylnidrical plug is cut from the agar forming a cup into which is pipetted a 10 percent agar dilution of mouthbenzyl ammonium chloride.
• ADC Agar Dilution Cup test
• aureus is poured on a base of 40 milliliters of sterile N-methyl-N-(Z-hydroxyethyl)-N-(2 hydroxydodecyl)- thioglycollate agar in a Petri dish.
• Calf skin discs are then N-benzyl ammonium chloride in a mouthwash formulahydrated in distilled water, agitated in themouthwash sotion was compared to commercially available quaternary lution and thoroughly rinsed in water for 15 minutes.
• ammonium compounds at various concentration levels by Excess water is removed from the disc which is then the testing procedures described above. The results, placed on the surface of the prepared seed agar plate.
• Bactericidal activity was determined by a Bactericidal Contact Time test (BCT) in which whole saliva from a group of donors is pooled and then 1 milliliter of pooled
• BCT Bactericidal Contact Time test
• a quaternary ammonium halide having at least one 2-hydroxyalkyl substituent characterized by the formula wherein R and R are selected from the group consisting of alkyl groups having from 1 to 3 carbon atoms and hydroxyalkyl groups having from 2 to 3 carbon atoms; R; is an alkyl radical having from 6 to 18 carbon atoms; X is selected from the group consisting of hydrogen and halogen; and Y is a halogen.

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Veterinary Medicine (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Oral & Maxillofacial Surgery (AREA)
• Birds (AREA)
• Epidemiology (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Cosmetics (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Agricultural Chemicals And Associated Chemicals (AREA)
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Cited By (6)

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• 1965
  • 1965-12-02 US US511247A patent/US3369046A/en not_active Expired - Lifetime
• 1966
  • 1966-11-30 SE SE16392/66A patent/SE348459B/xx unknown
  • 1966-11-30 DE DEU13316A patent/DE1274281B/de active Pending
  • 1966-12-01 AT AT1111866A patent/AT277967B/de not_active IP Right Cessation
  • 1966-12-01 BR BR185042/66A patent/BR6685042D0/pt unknown
  • 1966-12-01 FI FI3185/66A patent/FI43368B/fi active
  • 1966-12-01 DK DK624366AA patent/DK124399B/da unknown
  • 1966-12-01 ES ES0334038A patent/ES334038A1/es not_active Expired
  • 1966-12-01 NL NL6616961A patent/NL6616961A/xx unknown
  • 1966-12-01 NO NO165831A patent/NO116914B/no unknown
  • 1966-12-01 FR FR85822A patent/FR1504196A/fr not_active Expired
  • 1966-12-01 GB GB53767/66A patent/GB1156027A/en not_active Expired
  • 1966-12-02 CH CH1721866A patent/CH512430A/de not_active IP Right Cessation
  • 1966-12-02 LU LU52502D patent/LU52502A1/xx unknown
  • 1966-12-02 BE BE690625D patent/BE690625A/xx unknown

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