NZ772344A - A Disinfectant - Google Patents

A Disinfectant Download PDF

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Publication number
NZ772344A
NZ772344A NZ772344A NZ77234421A NZ772344A NZ 772344 A NZ772344 A NZ 772344A NZ 772344 A NZ772344 A NZ 772344A NZ 77234421 A NZ77234421 A NZ 77234421A NZ 772344 A NZ772344 A NZ 772344A
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New Zealand
Prior art keywords
disinfectant
use according
formula
duplicate
benzalkonium
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NZ772344A
Inventor
Hartley Campbell Atkinson
Original Assignee
Aft Pharmaceuticals Ltd
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Publication date
Application filed by Aft Pharmaceuticals Ltd filed Critical Aft Pharmaceuticals Ltd
Priority to NZ772344A priority Critical patent/NZ772344A/en
Priority to CN202180089311.8A priority patent/CN116782907A/en
Priority to PCT/NZ2021/050209 priority patent/WO2022164328A1/en
Publication of NZ772344A publication Critical patent/NZ772344A/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/02Local antiseptics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/13Amines
    • A61K31/14Quaternary ammonium compounds, e.g. edrophonium, choline
    • 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
    • A01N25/00Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/02Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing liquids as carriers, diluents or solvents
    • 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
    • A01N55/00Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur
    • AHUMAN NECESSITIES
    • A01AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01PBIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P1/00Disinfectants; Antimicrobial compounds or mixtures thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/075Ethers or acetals
    • A61K31/08Ethers or acetals acyclic, e.g. paraformaldehyde
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/075Ethers or acetals
    • A61K31/085Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/695Silicon compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34Alcohols
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34Alcohols
    • A61K8/345Alcohols containing more than one hydroxy group
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/40Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing nitrogen
    • A61K8/41Amines
    • A61K8/416Quaternary ammonium compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00Cosmetics or similar toiletry preparations
    • A61K8/18Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/58Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing atoms other than carbon, hydrogen, halogen, oxygen, nitrogen, sulfur or phosphorus
    • A61K8/585Organosilicon compounds
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0014Skin, i.e. galenical aspects of topical compositions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/08Solutions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/0005Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts
    • A61L2/0082Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor for pharmaceuticals, biologicals or living parts using chemical substances
    • A61L2/0088Liquid substances
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/16Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
    • A61L2/18Liquid substances or solutions comprising solids or dissolved gases
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61QSPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/005Antimicrobial preparations
    • 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
    • A01N25/00Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests
    • A01N25/22Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of application, e.g. seed treatment or sequential application; Substances for reducing the noxious effect of the active ingredients to organisms other than pests containing ingredients stabilising the active ingredients
    • 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
    • A01N33/00Biocides, pest repellants or attractants, or plant growth regulators containing organic nitrogen compounds
    • A01N33/02Amines; Quaternary ammonium compounds
    • A01N33/12Quaternary ammonium compounds
    • 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
    • A01N39/00Biocides, pest repellants or attractants, or plant growth regulators containing aryloxy- or arylthio-aliphatic or cycloaliphatic compounds, containing the group or, e.g. phenoxyethylamine, phenylthio-acetonitrile, phenoxyacetone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61LMETHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2101/00Chemical composition of materials used in disinfecting, sterilising or deodorising
    • A61L2101/32Organic compounds
    • A61L2101/34Hydroxy compounds

Abstract

A problem with many known disinfectants is that they do not provide protection on the skin for very long. It is an object of the invention to address this problem. The invention involves the use of Organosilane and Benzalkonium in the manufacture of a disinfectant comprising 0.2% - 0.4 % wt Organosilane and 0.08% – 0.12% wt Benzalkonium. The disinfectant is for providing, and provides, effective sanitising protection on human skin for about 24 hours or more.

Description

TITLE A Disinfectant FIELD OF INVENTION This invention relates to a long acting human skin disinfectant, for example for the hands.
BACKGROUND It is known to apply a disinfectant liquid to the human skin to kill germs, for example bacteria and virus’. A problem with many known disinfectants is that they are only effective for a short period and have to be reapplied frequently otherwise the person using them is relatively unprotected from infection if, for example, they touch a surface on which germs are located.
OBJECT OF THE ION It is an object of red embodiments of the invention to go at least some way towards sing the above problem. While this s to preferred embodiments, it should not be seen as a limitation on claims expressed more broadly. The object of the invention in its broadest form is simply to provide the public with a useful choice.
DEFINITIONS The term "comprises" or "has", if and when used in this document in relation to a combination of features, should not be seen as excluding the option of additional features in the combination that are not ned.
SUMMARY OF THE INVENTION According to one aspect the invention comprises the use of Organosilane and Benzalkonium in the manufacture of a ectant comprising: a) 0.2% - 0.4 % wt silane; and b) 0.08% – 0.12% wt Benzalkonium; wherein the disinfectant is for providing, and provides, effective sanitising protection* on human skin for about 24 hours or more.
* The term "effective sanitising protection" means that the disinfectant is kills ≥99% rably ≥99.99%) of germs on human skin.
Optionally the disinfectant ses: a) 0.25% - 0.35 % wt Organosilane; and b) 0.09% – 0.11% wt Benzalkonium.
Optionally the disinfectant comprises: a) about 0.3 % wt Organosilane; and b) about 0.1% wt Benzalkonium.
Optionally the Organosilane ses methoxysilyl)propyl dimethyl ocadecyl ammonium salt. ally the Organosilane comprises 3-(trimethoxysilyl)propyl dimethyl ocadecyl ammonium chloride. ally the Benzalkonium is in salt form.
Optionally the salt form comprises Benzalkonium Chloride.
Optionally the sanitising protection is against one or more of Coronavirus (eg SAARS-CoV-1 and/or SAARS-CoV-2), E.hirae, P.aeruginosa, S.aureus, E coli, Norovirus, Candida, MRSA, Salmonella, Listeria, Flu Virus and MHV1 virus.
Optionally the sanitising protection is against one or more of Enterococcus hirae, Pseudomonas nosa, Staphylococcus aureus and Escherichia coli.
Optionally the disinfectant comprises Phenoxyethanol which functions in the disinfectant as a preservative.
Optionally the Phenoxyethanol is present in the disinfectant at 0.7% - 1.3% wt.
Optionally the Phenoxyethanol is present in the disinfectant at 0.8% - 1.2% wt.
Optionally the Phenoxyethanol is present in the disinfectant at 0.9% - 1.1% wt.
Optionally the Phenoxyethanol is present in the disinfectant at about 1% wt.
Optionally the disinfectant comprises Ethylhexylglycerin which ons in the disinfectant as a preservative.
Optionally the Ethylhexylglycerin is present in the disinfectant at 0.07% - 0.13% wt.
Optionally the Ethylhexylglycerin is present in the ectant at 0.08% - 0.12% wt.
Optionally the Ethylhexylglycerin is t in the disinfectant at 0.09% - 0.11% wt.
Optionally the Ethylhexylglycerin is present in the disinfectant at about 0.1% wt.
Preferably the disinfectant is for application as a liquid to the skin liberally to provide the effective sanitising protection. For e an amount of 0.5 ml – 1 ml, and preferably about 0.75ml, was found to be sufficient for two hands of an adult male of average size.
DETAILED DESCRIPTION Three aqueous foaming disinfectant formulations were prepared to have the make-up shown in the tables below.
Formulation A INCI Name Function CAS No. % by Weight Water Solvent/Diluent 77325 to 100 Glycerin Humectant 565 2.0 yethanol Preservative 1226 0.9 Benzalkonium Chloride crobial 85-1 0.1 Ethylhexylglycerin Preservative 704459 0.1 3-(trimethoxysilyl)propyl Antimicrobial and 276686 0.1 dimethyl ocadecyl Surfactant ammonium chloride Formulation B INCI Name Function CAS No. % by Weight Water Solvent/Diluent 77325 to 100% Glycerin Humectant 565 2.0% Phenoxyethanol Preservative 1226 0.9% Benzalkonium Chloride Antimicrobial 684241 0.1% Ethylhexylglycerin Preservative 704459 0.1% 3-(trimethoxysilyl)propyl Antimicrobial and 276686 0.3% dimethyl ocadecyl Surfactant ammonium chloride Formulation C INCI Name Function CAS No. % by Weight Water Solvent/Diluent 77325 to 100% Glycerin Humectant 565 2.0% yethanol Preservative 1226 0.9% konium Chloride Antimicrobial 684241 0.1% exylglycerin Preservative 704459 0.1% 3-(trimethoxysilyl)propyl Antimicrobial and 276686 0.5% dimethyl ocadecyl Surfactant ammonium chloride In each case the ation was prepared as follows- Step 1 Dissolve all the the 3-(trimethoxysilyl)propyl dimethyl yl ammonium chloride in a sufficient portion of water so it makes up a pre-mix totaling about 6% weight of final product.
Step 2 Dissolve or suspend all the benzalkonium chloride in a sufficient portion of the water to provide a pre-mix solution or suspension totaling 0.2% weight of final product.
Step 3 In a separate mixing vessel, add water totaling 90.8% weight of the final product.
Step 4 Separately add each of the premixes (described in steps 1 and 2) to the water of step 3, and blend.
Step 5 Add all the yethanol and ethylhexylglycerin to the contents of the mixing vessel, and blend.
Step 6 Add all the glycerin to the components in the mixing vessel, and blend.
Step 7 Mix well (for ≥10 minutes) until all the ingredients are homogenized.
Tests for Disinfectant Performance Each formulation was tested to see how effective it was in g germs. This included a quantitative suspension test to evaluate bactericidal activity according to the well-known an test standard EN 13727. The formulations were also tested for virucidal ty by the surface carrier technique of ASTM 1053. Additionally, each formulation was subjected to tests to determine its effectiveness at 24 hours after being applied to human skin (hands).
The tests were carried out as follows.
Step 1 (Culture Growth) Two test organisms were selected and evaluated in the trial: • lococcus aureus NZRM 147 (ATCC 6538) • Escherichia coli NZRM 2577 (ATCC 8739) e suspensions were prepared for the organisms using overnight culture plates. The culture growth was harvested from each plate and inoculated to 10mL Tryptone Soy Broth (TSB) to achieve an approximate sm count of 109 cfu/mL.
Step 2 (Chemical Inactivation) A combination of neutraliser and on was used to achieve an ive neutralising system. In particular, Tryptone soy broth with 0.5% Lecithin and 4% Tween 20 (TLT) was used as a neutralising solution. Hand Sanitizer Formulation at ‘ready to use’ (RTU) concentration was diluted at a ratio of 1:1000 (10µL in 10mL TLT, the same volume and dilution ratio as treated Vitro-skin 2cm2). 10mL of the diluted formulation was then individually spiked to give a cell level sufficient to render a test organism tration within the countable range. In the presence of TLT the antimicrobial property of the test products was neutralized in order to recover any viable micro-organisms. The recovery of the test organism in the presence of test product was not less than 70% of that recovered from the inoculum l.
Step 3 In a Biological Safety Cabinet, two 2cm2 synthetic skin swatches were each pre-treated with 10µL of the test product at the RTU concentration. Each pair of skin swatches was rubbed together to distribute the test product, and dried under HEPA laminar air. The formulation remained on the swatches for sufficient time to demonstrate the residual efficacy of each test product. Duplicate tests were performed at each time point for all test products ding the nce product) and the water control.
Step 4 – (Water control - Baseline Control) The synthetic skin swatches were also eated with sterile water in the same manner as the test product, and tested at the same time points along-side the test product.
Step 5 At various time points, each treated skin swatch was inoculated with 10µL of culture suspension at an approximate concentration of 109 cfu/mL, and evenly distributed with a e 1µL loop. An re time of 5 minutes was allowed prior to transferring the skin swatch into neutralising broth (TLT).
Step 6 The inoculated neutralising broth was mixed and serially diluted to aid in determining the number of viable bacteria remaining.
Step 7 Step 5 and 6 were followed to test the water control in the same manner as the test product.
Step 8 The lised solutions for the test products and the water control were serially diluted using 0.1% Peptone, and each on was plated in duplicate using Standard Plate Count Agar.
Step 9 The plates were incubated at 35oC ± 1oC for 48 hours.
The tests gave the results detailed below.
Results Quantitative Suspension test for evaluating bactericidal activity Methodology: EN13727 Test Conditions (per EN13727) Test Concentration Neat Contact Time 1 Minute Formulation A: T6 1:10 (all organisms) Formulation B: T6 1:10 (all organisms) Neutralizer/Dilution Formulation C: T6 1:10 - E.coli, P.aeruginosa and E.hirae; T5 1:100 - S.aureus Test Conditions Clean (0.03% BSA) Test Temperature Room Temperature ing Organisms after re to each ation – 1 Minute Contact Time (per EN13727) Formulation Organism Inoculum Control ing Test Organisms Count CFU/mL CFU/mL Log reduction (Log10) ) Formulation A S.aureus 6.20 x 107 <10 >6.79 ATCC 6538 (7.79) (<1.00) E.coli 2.00 x 107 <10 >6.30 NCTC 10538 (7.30) (<1.00) P.aeruginosa 4.10 x 107 <10 >6.61 ATCC 15442 (7.61) (<1.00) E.hirae 3.90 x 107 <10 >6.59 ATCC 10541 (7.59) (<1.00) Formulation B S.aureus 2.35x 107 <10 >6.37 ATCC 6538 (7.37) <(1.00) E.coli 3.10 x 107 <10 >6.49 NCTC 10538 (7.49) <(1.00) P.aeruginosa 4.20 x 107 <10 >6.62 ATCC 15442 (7.62) <(1.00) E.hirae 1.55 x 107 <10 >6.19 ATCC 10541 (7.19) <(1.00) Formulation C S.aureus 4.85 x 107 <100 >5.69 ATCC 6538 (7.69) (<2.00) E.coli 3.65 x 107 <10 >6.56 NCTC 10538 (7.56) (<1.00) ginosa 2.60 x 107 <10 >6.41 ATCC 15442 (7.41) (<1.00) E.hirae 2.25 x 107 <10 >6.35 ATCC 10541 (7.35) ) CFU = Colony Forming Unit Neutralisation Validation Results (per EN13727) Formulation Validation Experimental lizer Method Suspension, Organism Condition, Control, Validation, Pass/Fail CFU/ml CFU/ml (A) CFU/ml (B) CFU/ml (C) Formulation A S.aureus 41 49 58 39 Pass ATCC 6538 E.coli 42 32 30 35 Pass NCTC 10538 P.aeruginosa 103 73 105 105 Pass ATCC 15442 E.hirae 23 22 23 31 Pass ATCC 10541 Formulation B S.aureus 24 16 44 13 Pass ATCC 6538 E.coli 31 16 82 98 Pass NCTC 10538 P.aeruginosa 42 27 74 56 Pass ATCC 15442 E.hirae 16 16 90 83 Pass ATCC 10541 Formulation C S.aureus 66 73 62 51 Pass ATCC 6538 E.coli 42 32 30 43 Pass NCTC 10538 P.aeruginosa 103 73 105 94 Pass ATCC 15442 23 22 23 17 Pass ATCC 10541 NV is the number of cells per ml in the tion suspension.
A, B and C are the numbers of surviving cells in the experimental ions control (A), neutralizer control (B) and method validation (C), at the end of the contact time A, B & C should preferably be ≥50% the value of Nv.
By way of summary, (TMD 110, 7), Formulations A and B showed greater than 6 log reduction t S.aureus, E.coli, P.aeruginosa and E.hirae at 1 minute contact time.
Formulation C showed greater than 6 log reduction against E.coli, P.aeruginosa and E.hirae and greater than 5 log reduction against S.aureus at 1 Minute contact time. All three formulas resulted in a >99.99% reduction in microorganisms after 1 minute contact.
Results of dal Test by Carrier Method Methodology: ASTM E1053 Test Conditions (ASTM E1053) Virus Strain Murine hepatitis virus (MHV1) ATCC/VR-261 Cell Substrate A9 cells ATCC/CCL- 1.4 Test Concentration Neat Contact Time 1 minute Test Temperature Room temperature Test Condition Clean Neutraliser 3 cc Sephadex Gel in PBS (Phosphate Buffer Saline) Formulation A: MHV1 test/control results (1 minute t) Number of Virus Virus Dilution Inoculated Cytotoxicity Neutralisation Test Sample Wells Control -1 4 4+/4 C C C -2 4 4+/4 0+/4 4+/4 3+/4 -3 4 4+/4 0+/4 4+/4 3+/4 -4 4 4+/4 N/A N/A 1+/4 -5 4 4+/4 N/A N/A 0+/4 -6 4 3+/4 N/A N/A 0+/4 -7 4 2+/4 N/A N/A N/A -8 4 0+/4 N/A N/A N/A Log10 - 6.77 1.5 1.5 3.33 Log10 Reduction of Virus after Treatment 3.44 ation B: MHV1 Test/Control Results (1 minute contact) Number of Virus Virus Dilution Inoculated xicity Neutralisation Test Sample Wells Control -1 4 4+/4 C C C -2 4 4+/4 0+/4 4+/4 4+/4 -3 4 4+/4 0+/4 4+/4 3+/4 -4 4 4+/4 N/A N/A 0+/4 -5 4 4+/4 N/A N/A 0+/4 -6 4 3+/4 N/A N/A 0+/4 -7 4 2+/4 N/A N/A N/A -8 4 0+/4 N/A N/A N/A Log10 - 6.77 1.5 1.5 3.33 Log10 Reduction of Virus after Treatment 3.44 Formulation C: MHV1 Test/Control Results (1 minute contact) Number of Virus Virus Dilution Inoculated Cytotoxicity Neutralisation Test Sample Wells Control -1 4 4+/4 C C C -2 4 4+/4 0+/4 4+/4 4+/4 -3 4 4+/4 0+/4 4+/4 4+/4 -4 4 4+/4 N/A N/A 1+/4 -5 4 4+/4 N/A N/A 0+/4 -6 4 3+/4 N/A N/A 0+/4 -7 4 2+/4 N/A N/A N/A -8 4 0+/4 N/A N/A N/A Log10 - 6.77 1.5 1.5 3.67 Log10 Reduction of Virus after ent 3.10 Note: Presence of virus is presented in a X+ of 4 format i.e. X+/4: X+ – number of wells (X) with presence of virus (+) 4 – total number of inoculated wells.
Example: In the event of a 3+/4 , this tes that 3 of the total 4 wells show a positive virus response.
Absence of virus in each response is recorded as "0" Cytotoxic response is recorded as "C" Calculated virus titre = 106.77TCID50/0.1ml (6.77 log10) Cell control - 4 wells with healthy cell monolayer * The Reed & Muench LD50 Method was used for determining the virus titre nt.
To summarise the results (TMCV 006, ASTM E1053), regarding cytotoxicity and neutralisation, the Formulations A and B showed virucidal efficacy against MHV1 by achieving 3.44 log reduction in virus concentration after 1 minute’s exposure period at room temperature. The formulations C also showed virucidal efficacy against MHV1 by achieving 3.10 log reduction in virus concentration after 1 minute’s exposure period at room temperature. This indicates that each formulation results in >99.9% reduction in viral count after 1 minute contact time, with as A and B exhibiting slightly better results than Formula C.
Results The 24-hour Residual Anti-Microbiological Study of the Hand Disinfectant t Methodology: The above Custom ro Study Protocol Test Conditions • Staphylococcus aureus NZRM 147 (ATCC 6538) Test Organism • ichia coli NZRM 2577 (ATCC 8739) Test Concentration Neat or Ready To Use Conditioning Time Points 5 minutes, 30 minutes, 1hr, 2hr, 4hr, 6hr and 24hr Contact Time 5 Minutes at each conditioning time point Tryptone soy broth with 0.5% Lecithin and 4% Tween 20 (TLT)/1:1000 Neutralizer/Dilution Dilution (10µL in 10mL TLT, same volume and dilution ratio as the treated 2cm2 synthetic skin substrate) Test Conditions In Biological Safety Cabinet, two 2cm2 synthetic skin es were each pre-treated with 10µL of the test t at the RTU concentration Test Temperature Ambient Temperature (defined as 20 ± 5˚C) • ASTM E3058 – 16: Standard Test Method for Determining the Residual Kill Activity of Hand Antiseptic Formulations.
• PAS2424:2014 – Quantitative surface test for the evaluation of residual antimicrobial ricidal and/or yeasticidal) efficacy of References liquid chemical disinfectants on hard non-porous surfaces – Test method .
• TGA instructions for disinfectant testing Version 2.1, March 2020.
• British Pharmacopoeia 2020 Appendix XVI C. Efficacy of Antimicrobial Preservation.
Neutraliser Validation 10µL in 10mL TLT (1 in 1,000 dilution) Formulation/Sample sm Average Recovery Result E.coli 70.6 103.5 Pass Formulation A S.aureus 67.8 105.3 Pass E.coli 69.4 101.8 Pass Formulation B S.aureus 61.6 95.7 Pass E.coli 68.6 100.6 Pass Formulation C S.aureus 67.4 104.7 Pass Reference E.coli 71.6 105.0 Pass Formulation S.aureus 66.8 103.7 Pass E.coli 68.2 N/A N/A Inoculum Control S.aureus 64.4 N/A N/A Residual Efficacy against Staphylococcus Aureus NZRM 147 (ATCC 6538) Conditioning Result Average Sample Log 10 Log Reduction Time Point (CFU/Swatch) result a A 00 19600000 7.29 0.12 Formula A duplicate 17700000 Formula B 15 1.18 6.24 Formula B duplicate <10 Formula C 16500000 minutes 00 7.22 0.20 a C duplicate 16550000 a Ref 28000000 27250000 7.44 -0.02 Formula Ref duplicate 26500000 Water control - Baseline 26000000 26000000 7.41 N/A Baseline duplicate 00 Formula A 24000000 23000000 7.36 -0.11 Formula A duplicate 22000000 Formula B 180 590 2.77 4.48 s Formula B ate 1000 Formula C 20000000 23250000 7.37 -0.12 Formula C duplicate 26500000 Formula Ref 28000000 26750000 7.43 -0.18 Formula Ref ate 25500000 Water control - Baseline 18500000 00 7.25 N/A Baseline duplicate 17000000 Formula A 21500000 21250000 7.33 0.17 Formula A duplicate 21000000 a B <10 380 2.58 4.92 Formula B duplicate 380 Formula C 32500000 1 hour 00 7.45 0.05 Formula C duplicate 24000000 Formula Ref 28000000 31250000 7.49 0.01 Formula Ref duplicate 34500000 Water l - Baseline 29500000 31750000 7.50 N/A Baseline duplicate 34000000 Formula A 31000000 28250000 7.45 -0.04 Formula A duplicate 25500000 Formula B 4200 4750 3.68 3.73 a B duplicate 5300 Formula C 29000000 2 hour 28500000 7.45 -0.05 Formula C duplicate 28000000 Formula Ref 25500000 27500000 7.44 -0.03 Formula Ref duplicate 29500000 Water control - Baseline 20500000 25500000 7.41 N/A Baseline duplicate 30500000 Formula A 00 29500000 7.47 -0.03 Formula A duplicate 32000000 Formula B 1700 4000 3.60 3.83 Formula B duplicate 6300 Formula C 35500000 4 hour 34000000 7.53 -0.10 Formula C duplicate 32500000 Formula Ref 00 28250000 7.45 -0.02 Formula Ref duplicate 30500000 Water control - Baseline 30000000 27250000 7.44 N/A Baseline duplicate 24500000 Formula A 22000000 31250000 7.49 0.03 Formula A duplicate 40500000 Formula B <10 <10 <1 >6.52 Formula B duplicate <10 Formula C 27500000 6 hour 28750000 7.46 0.06 a C duplicate 30000000 Formula Ref 00 30500000 7.48 0.04 Formula Ref duplicate 36500000 Water control - Baseline 39000000 33250000 7.52 N/A Baseline ate 27500000 Formula A 29500000 30500000 7.48 0.02 Formula A duplicate 31500000 a B 700 375 2.57 4.93 Formula B duplicate 50 Formula C 34500000 24 hour 35750000 7.55 -0.04 Formula C duplicate 37000000 Formula Ref 35000000 34000000 7.53 -0.02 Formula Ref duplicate 33000000 Water control - Baseline 29000000 32250000 7.51 N/A Baseline ate 00 Residual Efficacy t Escherichia Coli NZRM 2577 (ATCC 8739) Conditioning Result Average Sample Log 10 Log Reduction Time Point (CFU/Swatch) result Formula A 36500000 00 7.60 -0.03 a A duplicate 43000000 Formula B <10 <10 <1 >6.57 Formula B duplicate <10 Formula C 35500000 minutes 33500000 7.53 0.04 Formula C duplicate 31500000 Formula Ref 42000000 38000000 7.58 -0.01 Formula Ref duplicate 34000000 Water control - Baseline 37000000 36750000 7.57 N/A Baseline ate 36500000 Formula A 36500000 31750000 7.50 0.03 Formula A duplicate 27000000 Formula B <10 1.00 6.53 Formula B duplicate 10 a C 34500000 minutes 33750000 7.53 0.00 Formula C duplicate 33000000 Formula Ref 40000000 34000000 7.53 0.00 Formula Ref duplicate 28000000 Water control - Baseline 32500000 33750000 7.53 N/A Baseline duplicate 35000000 a A 34500000 27500000 7.44 0.04 Formula A duplicate 20500000 Formula B <10 <10 <1 >6.57 1 hour Formula B duplicate <10 Formula C 30500000 34750000 7.54 -0.06 Formula C duplicate 39000000 Formula Ref 24000000 18500000 7.27 0.22 Formula Ref duplicate 13000000 Water control - Baseline 34500000 30500000 7.48 N/A ne duplicate 26500000 Formula A 31000000 00 7.46 0.05 a A duplicate 27000000 Formula B 75 142.5 2.15 5.35 Formula B duplicate 210 Formula C 31500000 2 hour 32000000 7.51 0.00 Formula C duplicate 32500000 Formula Ref 39500000 33250000 7.52 -0.01 Formula Ref duplicate 27000000 Water control - Baseline 36500000 00 7.51 N/A Baseline duplicate 28000000 Formula A 45000000 36750000 7.57 0.07 Formula A duplicate 28500000 Formula B <10 234500 5.37 2.27 Formula B duplicate 234500 Formula C 30000000 4 hour 40000000 7.60 0.04 Formula C duplicate 50000000 a Ref 32500000 33750000 7.53 0.11 Formula Ref duplicate 35000000 Water control - Baseline 40500000 43500000 7.64 N/A Baseline ate 46500000 Formula A 34000000 35500000 7.55 0.04 a A duplicate 37000000 Formula B <10 <10 <1 >6.57 Formula B duplicate <10 Formula C 38500000 6 hour 00 7.59 0.00 Formula C duplicate 39000000 Formula Ref 23500000 24000000 7.38 0.21 Formula Ref duplicate 24500000 Water control - Baseline 41000000 38750000 7.59 N/A ne duplicate 36500000 a A 41000000 00 7.63 -0.10 Formula A duplicate 44500000 Formula B 102500 119250 5.08 2.46 Formula B duplicate 136000 Formula C 45500000 24 hour 44750000 7.65 -0.12 Formula C duplicate 44000000 Formula Ref 44000000 40500000 7.61 -0.07 Formula Ref duplicate 37000000 Water control - ne 36000000 34250000 7.53 N/A Baseline duplicate 35500000 Summary of al Efficacy Results (Formulation A) 24 hours Result Average Log 10 Log (cfu/swatch) result reduction (cfu/swatch) Staphylococcus Formula Repeat 1 29500000 30500000 0.02 aureus NZRM Repeat 2 31500000 147 (ATCC Water Repeat 1 29000000 32250000 7.51 6538) Control Repeat 2 00 24 hours Result Average Log 10 Log (cfu/swatch) result reduction (cfu/swatch) Escherichia Formula Repeat 1 41000000 42750000 coli NZRM Repeat 2 44500000 -0.10 2577 (ATCC Water Repeat 1 36000000 34250000 7.53 8739) Control Repeat 2 32500000 Summary of al Efficacy Results (Formulation B) 24 hours Result Average Log 10 Log (cfu/swatch) result ion (cfu/swatch) Staphylococcus Formula Repeat 1 700 375 2.57 4.93 aureus NZRM Repeat 2 50 147 (ATCC Water Repeat 1 29000000 32250000 7.51 6538) Control Repeat 2 35500000 24 hours Result Average Log 10 Log (cfu/swatch) result reduction (cfu/swatch) Escherichia a Repeat 1 102500 119250 5.08 2.46 coli NZRM Repeat 2 136000 2577 (ATCC Water Repeat 1 00 34250000 7.53 8739) Control Repeat 2 32500000 Summary of Residual Efficacy Results (Formulation C) 24 hours Result Average Log 10 Log (cfu/swatch) result reduction (cfu/swatch) Staphylococcus Formula Repeat 1 34500000 35750000 -0.04 aureus NZRM Repeat 2 37000000 147 (ATCC Water Repeat 1 29000000 32250000 7.51 6538) l Repeat 2 35500000 24 hours Result Average Log 10 Log (cfu/swatch) result reduction (cfu/swatch) ichia Formula Repeat 1 45500000 00 -0.12 coli NZRM Repeat 2 44000000 2577 (ATCC Water Repeat 1 00 34250000 7.53 8739) Control Repeat 2 32500000 By way of summary, Formulation B (at RTU volume) demonstrated residual efficacy with log reduction of between 2.27 and >6.57 throughout the 24 hour’s period (at 5 mins, 30 mins, 1hr, 2hr, 4hr, 6hr and 24hr) against Staphylococcus aureus NZRM 147 and Escherichia coli NZRM 2577. In comparison, Formulations A and C did not exhibit effective residual efficacy t either bacterial strain (maximum log reduction for either organism did not exceed 0.2 at any time point).
Formulation B demonstrated residual biocidal activity against both Staphylococcus aureus and Escherichia coli after 24 hours (4.93 and 2.46 log reduction, respectively). This translates to a >99.99% and >99% reduction in the count of Staphylococcus aureus and Escherichia coli, even if exposure to either sm occurs 24 hours after application of Formula B. Conversely, Formulation A exhibited a low log reduction against Staphylococcus aureus (0.02) after 24 hours, in addition to exhibiting a negative log reduction against Escherichia coli (-0.10), ting growth of organism. rly, Formula C resulted in negative log reductions against both Staphylococcus aureus (-0.04) and Escherichia coli (- 0.12) after 24 hours, ting organism growth.
This is significant as it indicates that Formula B exhibits al efficacy against microorganisms on tic skin, even after significant time has passed following application of the formula. This is believed to be related to a synergistic interaction provided by the Benzylkonium and Organosilane ingredients in Formulation B.
Other Forms of Benzlakonium While preferred ations according to the invention utilise Benzlakonium chloride, in other ments this may be substituted by other forms of Benzlakonium, for example Benzalkonium free base or one or more alternative Benzalkonium salts (e.g. Benzalkonium Bromide, Benzalkonium Saccharinate and Acesulfame Benzalkonium). In each case the weight amounts would be adjusted to provide more or less equivalent function.
Other Organosilanes Similarly, while preferred forms of the invention utilise 3-(trimethoxysilyl)propyl dimethyl ocadecyl um chloride, in other embodiments this may be substituted by other organosilanes, for example one or more of 3-(trihydroxysilyl) propyl yl octadecyl ammonium chloride (CAS 1991117) and n,n-dimethyl-n-[3-(trimethoxysilyl)propyl] tetradecanaminium chloride (CAS 415911). In each case the weight amounts would be ed to provide more or less equivalent function.
Preservatives, Humectants and Surfactants Further, formulations according to the invention may use alternative preservative, ant and/or surfactant materials to those of Formulations A, B and C, adjusting the weight amounts as appropriate to provide more less lent function. Examples of these are as follows – Preservative Humectant tants • Chlorhexidine gluconate • Propylene glycol • Alternative organosilanes, e.g. 3- • 1, 2-Hexanediol • Glycerol (trihydroxysilyl) propyl dimethyl • Benzoic acid • Aloe vera octadecyl ammonium chloride (CAS 1991117) and/or n,n-dimethyl-n- • Benzethonium chloride imethoxysilyl)propyl] • Ethylparaben tetradecanaminium de (CAS 415911) In terms of disclosure, this document hereby discloses each item, feature or step mentioned herein in combination with one or more of any of the other item, feature or step disclosed herein, in each case regardless of whether such combination is claimed.
While some preferred embodiments of the invention have been described by way of example it should be iated that modifications and improvements can occur without departing from the scope of the following claims.

Claims (24)

1. The use of Organosilane and Benzalkonium in the manufacture of a disinfectant sing: b) 0.2% - 0.4 % wt Organosilane; and c) 0.08% – 0.12% wt Benzalkonium; wherein the disinfectant is for providing, and provides, effective sanitising protection on human skin for about 24 hours or more.
2. The use according to claim 1, wherein the disinfectant comprises: a) 0.25% - 0.35 % wt Organosilane; and b) 0.09% – 0.11% wt Benzalkonium.
3. The use according to claim 1, wherein the disinfectant comprises: a) about 0.3 % wt Organosilane; and b) about 0.1% wt Benzalkonium.
4. The use according to claim 1, 2 or 3, wherein the Organosilane comprises 3- (trimethoxysilyl)propyl dimethyl ocadecyl ammonium salt.
5. The use according to claim 4, wherein the Organosilane comprises 3- (trimethoxysilyl)propyl dimethyl ocadecyl ammonium de.
6. The use according to any one of the preceding claims, wherein the Benzalkonium is in salt form.
7. The use according to claim 6, wherein the salt form comprises Benzalkonium de.
8. The use ing to any one of the preceding claims, wherein the sanitising protection is against Coronavirus.
9. The use according to any one of the preceding , wherein the sanitising protection is t SAARS-CoV-1 and/or SAARS-CoV-2 (eg CoVid-19 g Coronavirus).
10. The use according to any one of the preceding claims, comprising yethanol which functions in the disinfectant as a preservative.
11. The use according to claim 10, wherein the yethanol is present in the disinfectant at 0.7% - 1.3% wt.
12. The use according to claim 10, wherein the Phenoxyethanol is present in the disinfectant at 0.8% - 1.2% wt.
13. The use ing to claim 10, wherein the Phenoxyethanol is present in the disinfectant at 0.9% - 1.1% wt.
14. The use according to claim 10, wherein the Phenoxyethanol is present in the disinfectant at about 1% wt.
15. The use according to any one of the preceding , comprising Ethylhexylglycerin which functions in the disinfectant as a preservative.
16. The use according to claim 15, wherein the Ethylhexylglycerin is present in the disinfectant at 0.07% - 0.13% wt.
17. The use according to claim 15, wherein the Ethylhexylglycerin is t in the disinfectant at 0.08% - 0.12% wt.
18. The use according to claim 15, wherein the Ethylhexylglycerin is present in the disinfectant at 0.09% - 0.11% wt.
19. The use according to claim 15, wherein the Ethylhexylglycerin is present in the disinfectant at about 0.1% wt.
20. The use according to any one of the preceding claims, wherein the sanitising protection is against one or more of E.hirae, P.aeruginosa, S.aureus, E coli, Norovirus, Candida, MRSA, Salmonella, Listeria, Flu Virus and MHV1 virus.
21. The use according to any one of the ing claims, wherein the sanitising protection is against one or more of Enterococcus hirae, Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli.
22. The use according to any one of the preceding claims wherein the disinfectant is for providing, and provides, ive sanitising protection on human hands for about 24 or more hours.
23. A disinfectant prepared according to the use of any one of the preceding claims.
24. A disinfectant ntially as below- Component Approximate % by Weight Water to 100% Glycerin 2.0% Phenoxyethanol 0.9% Benzalkonium Chloride 0.1% Ethylhexylglycerin 0.1% 3-(trimethoxysilyl)propyl dimethyl 0.3% ocadecyl ammonium chloride Water to 100%
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CA2100670C (en) * 1991-02-15 1996-06-11 Richard W. Avery Production of stable aqueous hydrolyzable organosilane solutions
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