US20210161143A1 - Disinfectant composition - Google Patents

Disinfectant composition Download PDF

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US20210161143A1
US20210161143A1 US17/258,579 US201917258579A US2021161143A1 US 20210161143 A1 US20210161143 A1 US 20210161143A1 US 201917258579 A US201917258579 A US 201917258579A US 2021161143 A1 US2021161143 A1 US 2021161143A1
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olanexidine
antiseptic
formulation
gluconate
bactericidal
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Kaoru Imai
Hisae NISHIOKA
Akihumi HAGI
Shinji Oda
Kazumasa Hashimoto
Motoya Kikuchi
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Otsuka Pharmaceutical Co Ltd
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Otsuka Pharmaceutical Co Ltd
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Assigned to OTSUKA PHARMACEUTICAL FACTORY, INC. reassignment OTSUKA PHARMACEUTICAL FACTORY, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: IMAI, KAORU, NISHIOKA, Hisae, HAGI, Akihumi, HASHIMOTO, KAZUMASA, KIKUCHI, MOTOYA, ODA, SHINJI
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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides
    • A01N47/42—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides containing —N=CX2 groups, e.g. isothiourea
    • A01N47/44—Guanidine; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/02—Acyclic compounds
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals

Definitions

  • the present invention relates to an antiseptic composition (disinfectant composition) containing olanexidine gluconate and having a broader bactericidal spectrum.
  • Olanexidine chemical name 1-(3,4-dichlorobenzyl)-5-octylbiguanide
  • Olanexidine gluconate has sufficient water solubility, a broad bactericidal spectrum, demonstrates a bactericidal effect in a short time, further sustains such an effect for an extended period of time, and is highly safe, thereby to be useful as a medical disinfectant (Patent Document 1).
  • Dermal bactericidal disinfectants containing olanexidine gluconate have good efficacy on various bacteria which are considered as normal bacteria on skin and enveloped viruses, while substantially have no efficacy on feline calicivirus which has no envelope (Non-patent Document 1). For this reason, in the fields such as medical and nursing, and food and drink industries, olanexidine gluconate-containing disinfectants having more efficacies with a broader bactericidal spectrum are in demand.
  • Olanexidine belongs to monobiganide-based compounds which have 1 biganide structure.
  • Examples of the disinfectant having the same biganide structure representatively include chlorhexidine, which is a bisbiganide-based compound, and polyhexamethylene biguanide, which is a polybiganide-based compound.
  • Chlorhexidine is a bisbiganide-based compound having 2 biganide structures in a molecule. As with olanexidine, chlorhexidine is hardly water-soluble and becomes soluble in the form of gluconate, for the reason of which it is mainly used in the form of chlorhexidine gluconate as a pharmaceutical product (Non-patent Document 2). Chlorhexidine gluconate, as with olanexidine gluconate, shows a viricidal action on enveloped viruses, while having no efficacy on non-enveloped viruses (Non-patent Document 3).
  • chlorhexidine gluconate is stable at pH 4 to 6.5 and is known to cause precipitation when a dilute aqueous solution is basic of pH 8 or more and cause no difference in the bactericidal efficacies even when pH is increased (Patent Document 2, Non-patent Document 2, and Non-patent Document 4).
  • polyhexamethylene biganide classified as a polybiganide-based compound, is a polymer of hexamethylene biganide having 1 biganide structure in a unit.
  • Polyhexamethylene biganide is extremely easily soluble in water and has a broad bactericidal spectrum, for the reason of which a mild acidic solution thereof is commonly available as a low toxic sterilizing agent (Non-patent Documents 5 and 6).
  • Non-patent Document 7 commercial polyhexamethylene biganide disinfectants are reported as having viricidal activities on non-enveloped viruses (Non-patent Document 7) and further reported as increasing bactericidal efficacy and viricidal efficacy when pH is further increased (Non-patent Document 4 and Patent Documents 3 and 4).
  • An object of the present invention is to provide an antiseptic composition with a more extended applicable range by further enhancing the efficacy of olanexidine gluconate, which has been used as a highly safe dermal bactericidal disinfectant, and extending bactericidal spectrum.
  • Non-patent Document 1 Conventional bactericides containing olanexidine gluconate were formulated to be pH (Non-patent Document 1) because compositions applied to skins are generally mildly acidic according to pH (pH 4 to 7) of skins and olanexidine deposits in the form of a free compound when neutralized with an alkaline aqueous solution (Patent Document 1), however, the present inventors intentionally prepared a basic solution of olanexidine gluconate to test activities thereof and found that bactericidal efficacies are not only unexpectedly enhanced but efficacies are demonstrated on non-enveloped viruses against which a mildly acidic formulation thereof had substantially no efficacy. Further, the present inventors confirmed that further addition of a surfactant to a basic solution containing olanexidine gluconate enhances the stability. The present invention is based on the above findings.
  • the present invention is as follows.
  • a disinfectant usable in the fields such as medical and nursing, and food and drink industries and having higher efficacy with a broader bactericidal spectrum can be produced.
  • FIG. 1 is a chart showing bactericidal powers of olanexidine gluconate-containing compositions (pH 5, 8 to 10) of Example 1 against Mycobacterium fortuitum JCM 6387.
  • FIG. 2 is a chart showing bactericidal powers of olanexidine gluconate-containing compositions (pH 5, 8 to 10) of Example 1 against Mycobacterium chelonae JCM 6388.
  • FIG. 3 is a chart showing bactericidal powers of olanexidine gluconate-containing compositions (pH 5, 8 to 10) of Example 1 against Microsporum canis NBRC 32464.
  • FIG. 4 is a chart showing viricidal (phage) activities of olanexidine gluconate-containing compositions (pH 5, 7 to 12) of Example 2 on phage.
  • FIG. 5 is a chart showing a viricidal (phage) activity of ethanol-containing olanexidine formulation of Example 3 on phage.
  • the present invention relates to an antiseptic composition which comprises olanexidine gluconate and is basic.
  • Being basic used herein may be any composition of pH being more than 7 but examples include, in view of toxicity and a bactericidal activity to skins, pH being more than 7 to 12, pH being more than 7 to 11.5, pH being more than 7 to 11, pH being more than 7 to 10.5, and pH being more than 7 to 10; preferably pH 7.5 to 12, pH 7.5 to 11.5, pH 7.5 to 11, pH 7.5 to 10.5, and pH 7.5 to 10; more preferably pH 8 to 11.5, pH 8 to 11, pH 8 to 10.5, pH 8 to 10; further preferably pH 8.5 to 11.5, pH 8.5 to 11, pH 8.5 to 10.5, and pH 8.5 to 10; and furthermore preferably pH 9 to 12, pH 9 to 11.5, pH 9 to 11, pH 9 to 10.5, and pH 9 to 10.
  • the composition of the present invention is an aqueous solution.
  • the “disinfection” and “bactericidal” mean to kill bacteria, fungi
  • any known pH adjuster can be used to adjust the pH, but examples include a basic solution such as sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonium carbonate, and potassium carbonate, of which sodium hydroxide is preferable.
  • the composition of the present invention is optionally prepared using a basic buffer, and examples of the buffer used include a boric acid-sodium carbonate buffer, a CAPS-NaOH buffer, a Bicine-NaOH buffer, a Glycine-NaOH buffer, a Tricine-NaOH buffer, a HEPPS-NaOH buffer, a TAPS-NaOH buffer, a Bicine-NaOH buffer, and a HEPES-NaOH buffer.
  • the concentration of olanexidine gluconate is not particularly limited as long as it has sufficient bactericidal efficacy, but examples include 0.01 to 20% (W/V), preferably 0.1 to 10% (W/V), and more preferably 0.5 to 5% (W/V).
  • examples of such a concentration include 0.01 to 10% (W/V), preferably 0.1 to 7% (W/V), more preferably 0.5 to 5% (W/V), and further preferably 0.5 to 3% (W/V).
  • a composition of the present invention has more promoted bactericidal activities on filamentous fungi and acid-fast bacteria, particularly bacteria of the genus Microsporum and bacteria of the genus Mycobacterium. Further, the present composition also has good viricidal activities even on non-enveloped viruses, particularly viruses of the family Caliciviridae (viruses of the genus Norovirus ), against which the conventional olanexidine gluconate-containing disinfectants failed to inactivate.
  • a composition of the present invention further optionally contains an antiseptic alcohol to potentiate bactericidal activities and impart quick-dryness.
  • the antiseptic alcohol herein preferably include ethanol and isopropyl alcohol, and examples of the antiseptic alcohol concentration include 10 to 85% (V/V), 20 to 85% (V/V), 30 to 85% (V/V), 40 to 85% (V/V), 50 to 85% (V/V), 10 to 80% (V/V), 20 to 80% (V/V), 30 to 80% (V/V), 40 to 80% (V/V), 50 to 80% (V/V), 10 to 70% (V/V), 20 to 70% (V/V), 30 to 70% (V/V), 40 to 70% (V/V), and 50 to 70% (V/V).
  • a composition of the present invention may not substantially contain an antiseptic alcohol.
  • Containment of the antiseptic alcohol enables to prepare a quick-drying disinfectant having both potentiating effects of bactericidal activities due to the antiseptic alcohol and sustained effects of bactericidal activities due to olanexidine gluconate. Further, as bactericidal activities are potentiated due to the antiseptic alcohol, a concentration of olanexidine gluconate can be reduced. Examples of the concentration ratio of the olanexidine gluconate to the antiseptic alcohol include 1:400 to 1:20, preferably 1:300 to 1:30, and more preferably 1:200 to 1:40.
  • a composition of the present invention can further contain a known bactericide.
  • the bactericide include a benzalkonium salt such as benzalkonium chloride and benzalkonium alkyl phosphate, benzethonium chloride, triclosan, isopropyl methylphenol, cetylpyridinium chloride, resorcin, trichlorocarbanilide, chlorhexidine hydrochloride, chlorhexidine gluconate, polyhexamethylene biganide, sodium hypochlorite, hydrogen peroxide, povidone iodine, and iodine tincture.
  • These bactericides are optionally used singly or 2 or more may be used in combination.
  • a composition of the present invention can further contain a known solubilizer.
  • the solubilizer include a nonionic surfactant, an ionic surfactant, ethylenediamine, sodium benzoate, nicotinamide, cyclodextrin, ethanol, benzyl alcohol, and propylene glycol.
  • the ionic surfactant preferably include an alkyl dimethylamine oxide such as an oleyl dimethylamine oxide, a stearyl dimethylamine oxide, a palmityl dimethylamine oxide, a myristyl dimethylamine oxide, a lauryl dimethylamine oxide, and a coconut oil alkyl dimethylamine oxide, of which a lauryl dimethylamine oxide is preferable.
  • nonionic surfactant examples include a sorbitan fatty acid ester, a polyoxyethylene sorbitan fatty acid ester, a polyoxyethylene alkyl ether, a polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene polyoxypropylene glycol, a polyglyceryl fatty acid ester, a polyoxyethylene hydrogenated castor oil, and a sucrose fatty acid ester, of which polyoxyethylene polyoxypropylene glycol, a polyoxyethylene alkyl ether, and a polyoxyethylene polyoxypropylene alkyl ether are preferable.
  • polyoxyethylene polyoxypropylene glycol examples include polyoxyethylene(42) polyoxypropylene(67) glycol (Pluronic (R) P-123), polyoxyethylene(54) polyoxypropylene(39) glycol (Pluronic (R) P-85), polyoxyethylene(196) polyoxypropylene (67) glycol (Pluronic (R) F-127), polyoxyethylene(3) polyoxypropylene(17) glycol (Pluronic (R) L-31), polyoxyethylene(20) polyoxypropylene(20) glycol (Pluronic (R) L-44), polyoxyethylene(120) polyoxypropylene(40) glycol (Pluronic (R) F-87), and polyoxyethylene(160) polyoxypropylene(30) glycol (Pluronic (R) F-68), of which polyoxyethylene(20) polyoxypropylene(20) glycol (Pluronic (R) L-44) is preferable.
  • polyoxyethylene alkyl ether examples include a polyoxyethylene cetylether, a polyoxyethylene oleyl ether, and a polyoxyethylene lauryl ether (lauromacrogol), with a polyoxyethylene lauryl ether (lauromacrogol) being particularly preferable.
  • polyoxyethylene polyoxypropylene alkyl ether examples include a polyoxyethylene(20) polyoxypropylene(4) cetylether, a polyoxyethylene(30) polyoxypropylene(6) decyltetradecyl ether, a polyoxyethylene(25) polyoxypropylene(25) lauryl ether, with a polyoxyethylene(20) polyoxypropylene(4) cetylether being particularly preferable.
  • the concentration of a solubilizer may be a concentration which prevents olanexidine gluconate from precipitating and does not reduce the bactericidal activity and is usually determined in accordance with a concentration of olanexidine gluconate within a concentration range of 0.1 to 30% (W/V).
  • a composition of the present invention optionally contains an anti-inflammatory agent, a moisturizer, an emollient agent, a touch improver, and a thickener.
  • anti-inflammatory agent examples include a licorice extract, glycyrrhetinic acid, dipotassium glycyrrhizinate, stearyl glycyrrhetinate, tocopherol acetate, allantoin, and an aloe extract.
  • Example of the moisturizer include an amino acid, a fatty acid ester, pyrrolidone carboxylic acid, sodium pyrrolidone carboxylate, sodium lactate, hyaluronic acid, sodium hyaluronate, N-cocoyl-L-arginine ethyl ester-DL-pyrrolidone carboxylate, urea, sorbitol, trehalose, 1,3-butylene glycol, propylene glycol, poloxamer (Pluronic (R) F-68, etc.), and glycerin.
  • a fatty acid ester pyrrolidone carboxylic acid, sodium pyrrolidone carboxylate, sodium lactate, hyaluronic acid, sodium hyaluronate, N-cocoyl-L-arginine ethyl ester-DL-pyrrolidone carboxylate, urea, sorbitol, trehalose, 1,3-butylene glyco
  • emollient examples include a fatty acid ester such as isopropyl myristate, isopropyl palmitate, isopropyl stearate, isobutyl oleate, and isobutyl maleate, and 1 fatty acid ester singly or 2 or more of these can be contained.
  • a fatty acid ester such as isopropyl myristate, isopropyl palmitate, isopropyl stearate, isobutyl oleate, and isobutyl maleate, and 1 fatty acid ester singly or 2 or more of these can be contained.
  • Examples of the touch improver include a silicone-based compound such as dimethylpolysiloxane and cyclic silicone.
  • the thickener examples include a cellulose derivative such as hydroxyethyl cellulose, hydroxypropyl cellulose, hydrophobic hydroxypropyl methylcellulose, methyl cellulose, and carboxymethyl cellulose, a (meth)acrylic acid base copolymer, polyvinyl alcohol, polyvinylpyrrolidone, a methyl vinyl ether-maleic anhydride copolymer, polyacrylamide, alginic acid, sodium alginate, propylene glycol alginate, gelatin, a gum arabic, a gum tragacanth, a locust bean gum, a guar gum, a tamarind gum, a xanthan gum, a gellan gum, and carrageenan.
  • a cellulose derivative such as hydroxyethyl cellulose, hydroxypropyl cellulose, hydrophobic hydroxypropyl methylcellulose, methyl cellulose, and carboxymethyl cellulose
  • a (meth)acrylic acid base copolymer polyvin
  • a composition of the present invention can preferably be used for the purpose of disinfecting the instrument surfaces of medical instruments, cookware, and nursing equipment, and skin surfaces such as hands and fingers.
  • a composition of the present invention is optionally used as soaked in paper, cloth, non-woven fabric, cotton swab, or absorbent cotton, or as filled in an applicator for application, or in the form of a rubbing agent or a scrubbing agent, but a composition of the present invention is preferably used as a rubbing agent.
  • the rubbing agent herein means a quick-drying rubbing-type formulation
  • the scrubbing agent means a formulation obtained by mixing a bactericide/disinfectant and a surfactant having detergency.
  • an amount usually used per disinfection is 1 to 5 ml, preferably 1.5 to 4.5 ml, more preferably 2 to 4 ml, and further preferably 2.5 to 3.5 ml, and examples of the number of times used per day include, in view of dermal toxicity, within 100 times, preferably within 80 times, more preferably within 60 times, and further preferably within 40 times.
  • Substance to be tested 1 Name: Olanexidine formulation pH 5 Composition: Olanexidine gluconate 1.5% (W/V) Pluronic L-44 1.08% (W/V) pH Adjuster (sodium hydroxide, glucono- ⁇ -lactone) qs Pure water qs pH 5 (2) Substance to be tested 2 Name: Olanexidine formulation pH 8 Composition: Olanexidine gluconate 1.5% (W/V) Pluronic L-44 1.08% (W/V) HEPES 0.1% (W/V) pH Adjuster (sodium hydroxide, glucono- ⁇ -lactone) qs Pure water qs pH 8 (3) Substance to be tested 3 Name: Olanexidine formulation pH 9 Composition: Olanexidine gluconate 1.5% (W/V) Pluronic L-44 4.08% (W/V) Glycine 0.1% (W/V) pH Adjuster (sodium hydroxide, glucono- ⁇ -lactone) qs Pure water qs
  • test microorganisms filamentous fungus Microsporum canis NBRC 32464, acid-fast bacteria Mycobacterium chelonae JCM 6388 and Mycobacterium fortuitum JCM 6387 were used.
  • Each of the test microorganisms was cultured on the 7H10 plate ( Mycobacterium chelonae and Mycobacterium fortuitum ) or the SAB plate ( Microsporum canis ), and then suspended in distilled water to prepare test microorganism solutions of McFarland No.1 ( Mycobacterium chelonae and Mycobacterium fortuitum ) or of McFarland No.5 ( Microsporum canis ).
  • the mixing ratio of the reaction solution to the neutralizer is 1:99 and the smear amount is 100 ⁇ L, because of which the minimum limit of detection of a viable cell count is 1000 CFU/mL (3 in common logarithm value). Further, with Microsporum canis, the mixing ratio of the reaction solution to the neutralizer is 1:9 and the smear amount is 100 ⁇ L, because of which the minimum limit of detection of a viable cell count is 100 CFU/mL (2 in common logarithm value). When a colony was not detected, the minimum limit of detection was adopted and LR is indicated with a sign of inequality “>”.
  • Bacteriophage MS2 is known to be resistant to disinfectants and is used for an alternative test such as the norovirus killing action of disinfectants. For this reason, viricidal effects of the olanexidine formulations prepared by changing pH and a commercial disinfectant on a virus were evaluated by a test using bacteriophage MS2.
  • Substance to be tested 1 Name: Olanexidine formulation pH 5 Composition: Olanexidine gluconate 1.5% (W/V) Pluronic L-44 1.08% (W/V) pH Adjuster (sodium hydroxide, glucono- ⁇ -lactone) qs Pure water qs pH 5 (2) Substance to be tested 2 Name: Olanexidine formulation pH 7 Composition: Olanexidine gluconate 1.5% (W/V) Pluronic L-44 1.08% (W/V) HEPES 0.1% (W/V) pH Adjuster (sodium hydroxide, glucono- ⁇ -lactone) qs Pure water qs pH 7 (3) Substance to be tested 3 Name: Olanexidine formulation pH 8 Composition: Olanexidine gluconate 1.5% (W/V) Pluronic L-44 1.08% (W/V) HEPES 0.1% (W/V) pH Adjuster (sodium hydroxide, glucono- ⁇ -lactone) qs Pure water qs
  • a phage solution prepared to about 6 ⁇ 10 12 PFU/mL in accordance with a routine method was used.
  • Phage titer was calculated using the following (Equation 1).
  • a titer (PFU/mL) was converted to common logarithm (log 10 PFU/mL) and indicated to the first decimal place by rounding off. When a titer (PFU/mL) was 1 or less, its common logarithm value was 0.
  • the viricidal (phage) action was evaluated by a Log 10 reduction value.
  • LR is indicated to the first decimal place by rounding off. Note that when a titer (common logarithm value) of the test substance after acted was 0, LR is indicated as “>(A ⁇ 3)” because the phage titer has the minimum limit of detection of 3 ⁇ log 10 .
  • Evaluation results on the viricidal actions of the test substances are shown in Table 4 and FIG. 4 .
  • the olanexidine formulation at pH 5 did not substantially show the viricidal action, and the viricidal action of the olanexidine formulation at pH 7 was equal to 70% ethanol used as the control substance, whereas the olanexidine formulations with the pH changed to basic tended to have larger LR as pH increased.
  • the formulations at pH 8 or more had an LR of 3 or higher at 60 seconds and the formulation at pH 8.5 or more had an LR of 3 or higher at 30 seconds thereby to meet a requirement for the viricidal action of an ideal disinfectant of LR 3 or higher.
  • a basic solution of olanexidine gluconate was revealed to have a practical viricidal activity and such a viricidal activity is intensified as pH increases.
  • ethanol was added to a basic olanexidine formulation of pH 9.5 to evaluate a viricidal effect by a test using bacteriophage MS2 for the purpose of confirming the quick-dryness imparting effect and the potentiating effect of the bactericidal activity by an antiseptic alcohol to a basic olanexidine formulation.
  • Viricidal effects were evaluated by the method using the bacteriophage MS2 described in the above Example 2, 2-1 and 2-2. Note that a phage solution prepared to about 4 ⁇ 10 12 PFU/mL was used.
  • Evaluation results on viricidal actions of the test substances are shown in Table 6 and FIG. 5 .
  • the above results showed that the viricidal action increases in a concentration dependent manner of olanexidine gluconate even in the basic olanexidine formulation containing ethanol whereby the viricidal action by olanexidine gluconate is not impeded even when ethanol is added to impart quick-dryness.
  • the basic olanexidine formulation containing ethanol has a higher viricidal action compared with a basic olanexidine formulation which does not contain ethanol, for the reason of which the ethanol-containing basic olanexidine formulation showed to have a practical viricidal action even when an olanexidine gluconate concentration is reduced.
  • composition of the present invention when used, can produce an olanexidine gluconate-containing disinfectant having an improved bactericidal spectrum and an effect on non-enveloped viruses and is thus highly useful in the fields such as medical and nursing, and food and drink industries.

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JPWO2020017473A1 (ja) 2021-08-02
CN112351684A (zh) 2021-02-09
AU2019307996A1 (en) 2020-12-10
JP7006991B2 (ja) 2022-01-24
CA3102757A1 (fr) 2020-01-23
PH12021550071A1 (en) 2021-09-27
AU2019307996B2 (en) 2024-03-14
SG11202012238WA (en) 2021-01-28
TW202005537A (zh) 2020-02-01
EP3824734B1 (fr) 2023-03-01
EP3824734A4 (fr) 2022-03-30
CN112351684B (zh) 2022-09-23
EP3824734A1 (fr) 2021-05-26

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