WO1998055081A2 - Composition nettoyante liquide antimicrobienne douce a conserver - Google Patents
Composition nettoyante liquide antimicrobienne douce a conserver Download PDFInfo
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- WO1998055081A2 WO1998055081A2 PCT/US1998/010978 US9810978W WO9855081A2 WO 1998055081 A2 WO1998055081 A2 WO 1998055081A2 US 9810978 W US9810978 W US 9810978W WO 9855081 A2 WO9855081 A2 WO 9855081A2
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- 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
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/365—Hydroxycarboxylic acids; Ketocarboxylic acids
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- 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
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/347—Phenols
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- 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
- A61K8/46—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur
- A61K8/463—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur containing sulfuric acid derivatives, e.g. sodium lauryl sulfate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q17/00—Barrier 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
- A61Q17/005—Antimicrobial preparations
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
Definitions
- the present invention relates to leave-on, topical antimicrobial compositions which provide improved antimicrobial effectiveness when they are applied to the skin.
- the leave-on antimicrobial compositions of the invention provide provide previously unseen residual effectiveness against transient Gram negative bacteria, previously unseen levels of residual effectiveness against Gram positive bacteria, provide improved immediate germ reduction on the skin compared to prior art compositions.
- Resident bacteria are Gram positive bacteria which are established as permanent microcolonies on the surface and outermost layers of the skin and play an important, helpful role in preventing the colonization of other, more harmful bacteria and fungi.
- Transient bacteria are bacteria which are not part of the normal resident flora of the skin, but can be deposited when airborne contaminated material lands on the skin or when contaminated material is brought into physical contact with it.
- Transient bacteria are typically divided into two subclasses: Gram positive and Gram negative.
- Gram positive bacteria include pathogens such as Staphylococcus aureus, Streptococcus pyogenes and Clostridium botulinum.
- Gram negative bacteria include pathogens such as Salmonella, Escherichia coli, Klebsiella, Haemophilus, Pseudomonas aeruginosa, Proteus and Shigella dysenteriae.
- Gram negative bacteria are generally distinguished from Gram positive by an additional protective cell membrane which generally results in the Gram negative bacteria being less susceptible to topical antibacterial actives.
- Antimicrobial cleansing products have been marketed in a variety of forms, for some time. Forms include antibacterial soaps, hard surface cleaners, and surgical disinfectants. Rinse-off antimicrobial soaps have been formulated to provide bacteria removal during washing. Antimicrobial liquid cleansers are disclosed in U.S. Patent Numbers: 4,847,072, Bissett et al., issued July 11, 1989, 4,939,284, Degenhardt, issued July 3, 1990 and 4,820,698, Degenhardt, issued April 11, 1989, all patents being incorporate herein by reference. Finally, these traditional antimicrobial soaps have been developed for use in a washing process with water. This limits their use to locations with available water.
- Some of these traditional products especially the hard surface cleaners, surgical disinfectants, and some alcohol-based leave-on lotions (e.g. Purell®), utilize high levels of alcohol and/or harsh surfactants which have been shown to dry out and irritate skin tissues. Ideal personal cleansers should gently cleanse the skin, cause little or no irritation, and not leave the skin overly dry after frequent use and preferably should provide a moisturizing benefit to the skin.
- Leave-on, topical lotions, foams and gels have been used, in the past, to moisturize skin, along with a variety of other purposes. However, these leave-on compositions provide minimal antimicrobial effectiveness.
- leave-on, topical antimicrobial compositions which provide such mildness and antimicrobial effectiveness can be formulated by using known antimicrobial actives in combination with specific organic and/or inorganic acids as proton donating agents, and specific anionic surfactants, all of which are deposited on the skin.
- the deposited proton donating agent and anionic surfactant work in combination with the selected active, to provide a new level of hostility to bacteria contacting the skin.
- the present invention relates to a leave-on antimicrobial composition characterized in that it comprises from 0.001% to 5% of an antimicrobial active; from 0.05% to 10% of an anionic surfactant; from 0.1% to 10% of a proton donating agent; and from 0% to 99.85% of water; wherein the composition is adjusted to a pH of from 3.0 to 6.0; wherein the leave-on antimicrobial composition has a Gram Negative Residual Effectiveness Index of greater than 0.3; and wherein the leave-on antimicrobial composition has a Mildness Index of greater than 0.3.
- the present invention also relates to a leave-on antimicrobial cleansing composition which has a Gram Positive Residual Effectiveness Index of greater than 0.5. It also relates to a leave-on antimicrobial cleansing composition which has a One-wash Immediate Germ Reduction Index of greater than 1.0.
- the present invention also relates to methods for decreasing the spread of transient Gram positive bacteria using the leave-on antimicrobial compositions described herein.
- the leave-on antimicrobial compositions of the present invention are highly efficacious for providing residual antimicrobial effectiveness versus Gram negative bacteria, residual antimicrobial effectiveness versus transient Gram positive bacteria, or for reducing the number of germs on the skin; and are mild to the skin.
- leave-on antimicrobial composition is used herein to mean products suitable for application to the human skin for the purpose controlling the growth and viability of transient bacteria on the skin.
- residual effectiveness it is meant that bacteria growth on a surface is controlled for some period of time following the washing/rinsing process.
- compositions of the present invention can also be useful for treatment of acne.
- treating acne means preventing, retarding and/or arresting the process of acne formation in mammalian skin.
- the compositions of the invention can also potentially be useful for providing an essentially immediate (i.e., acute) visual improvement in skin appearance following application of the composition to the skin.
- the compositions of the present invention are useful for regulating skin condition, including regulating visible and/or tactile discontinuities in skin, including but not limited to visible and/or tactile discontinuities in skin texture and/or color, more especially discontinuities associated with skin aging. Such discontinuities may be induced or caused by internal and/or external factors.
- Extrinsic factors include ultraviolet radiation (e.g., from sun exposure), environmental pollution, wind, heat, low humidity, harsh surfactants, abrasives, and the like.
- Intrinsic factors include chronological aging and other biochemical changes from within the skin.
- Regulating skin condition includes prophylactically and/or therapeutically regulating skin condition.
- prophylactically regulating skin condition includes delaying, minimizing and/or preventing visible and/or tactile discontinuities in skin.
- therapeutically regulating skin condition includes ameliorating, e.g., diminishing, minimizing and/or effacing, such discontinuities.
- Regulating skin condition involves improving skin appearance and/or feel, e.g., providing a smoother, more even appearance and/or feel.
- regulating skin condition includes regulating signs of aging.
- Regular signs of skin aging includes prophylactically regulating and/or therapeutically regulating one or more of such signs (similarly, regulating a given sign of skin aging, e.g., lines, wrinkles or pores, includes prophylactically regulating and/or therapeutically regulating that sign).
- “Signs of skin aging” include, but are not limited to, all outward visibly and tactilely perceptible manifestations as well as any other macro or micro effects due to skin aging. Such signs may be induced or caused by intrinsic factors or extrinsic factors, e.g., chronological aging and/or environmental damage.
- These signs may result from processes which include, but are not limited to, the development of textural discontinuities such as wrinkles, including both fine superficial wrinkles and coarse deep wrinkles, skin lines, crevices, bumps, large pores (e.g., associated with adnexal structures such as sweat gland ducts, sebaceous glands, or hair follicles), scaliness, flakiness and or other forms of skin unevenness or roughness, loss of skin elasticity (loss and or inactivation of functional skin elastin), sagging (including puffiness in the eye area and jowls), loss of skin firmness, loss of skin tightness, loss of skin recoil from deformation, discoloration (including undereye circles), blotching, sallowness, hyperpigmented skin regions such as age spots and freckles, keratoses, abnormal differentiation, hyperkeratinization, elastosis, collagen breakdown, and other histological changes in the stratum corneum, dermis, epidermis, the skin
- the leave-on antimicrobial compositions of the present invention comprise an antimicrobial active, an anionic surfactant, and a proton donating agent. These components are selected so that the efficacy and mildness requirements hereinafter defined for the compositions herein are met. The selection of each component is necessarily dependent on the selection of each of the other components. For example, if a weak acid is selected as the proton donating agent, then in order to realize an efficacious composition, either a more biologically active (but possibly less mild) surfactant must be employed, and/or a high level of acid within the prescribed range must be used and/or a particularly efficacious active must be employed.
- the leave-on antimicrobial composition of the present invention comprises from 0.001% to 5%, preferably from 0.05% to 1%, more preferably from 0.05% to 0.5% and more preferably from 0.1% to 0.25%), by weight of the leave-on antimicrobial composition, of an antimicrobial active.
- an antimicrobial active preferably from 0.05% to 1%, more preferably from 0.05% to 0.5% and more preferably from 0.1% to 0.25%
- the exact amount of antibacterial active to be used in the compositions will depend on the particular active utilized since actives vary in potency. Non-cationic actives are required in order to avoid interaction with the anionic surfactants of the invention.
- non-cationic antimicrobial agents which are useful in the present invention .
- Methanamine Methyldibromonitrile Glutaronitrile (l,2-Dibromo-2,4-dicyanobutane or Tektamer®)
- Phenethyl Alcohol o-Phenylphenol/sodium o-phenylphenol
- PCMX Para-chloro-meta-xylenol
- natural antibacterial actives are the so-called "natural" antibacterial actives, referred to as natural essential oils. These actives derive their names from their natural occurrence in plants.
- natural essential oil antibacterial actives include oils of anise, lemon, orange, rosemary, wintergreen, thyme, lavender, cloves, hops, tea tree, citronella, wheat, barley, lemongrass, cedar leaf, cedarwood, cinnamon, fleagrass, geranium, sandalwood, violet, cranberry, eucalyptus, vervain, peppermint, gum benzoin, basil, fennel, fir, balsam, menthol, ocmea origanum, Hydastis carradensis, Berberidaceae daceae, Ratanhiae and Curcuma longa.
- Also included in this class of natural essential oils are the key chemical components of the plant oils which have been found to provide the antimicrobial benefit. These chemicals include, but are not limited to anethol, catechole, camphene, carvacol, eugenol, eucalyptol, ferulic acid, farnesol, hinokitiol, tropolone, limonene, menthol, methyl salicylate, thymol, terpineol, verbenone, berberine, ratanhiae extract, caryophellene oxide, citronellic acid, curcumin, nerolidol and geraniol.
- anethol catechole, camphene, carvacol, eugenol, eucalyptol, ferulic acid, farnesol, hinokitiol, tropolone, limonene, menthol, methyl salicylate, thymol, terpineol, verb
- Additional active agents are antibacterial metal salts.
- This class generally includes salts of metals in groups 3b-7b, 8 and 3a-5a. Specifically are the salts of aluminum, zirconium, zinc, silver, gold, copper, lanthanum, tin, mercury, bismuth, selenium, strontium, scandium, yttrium, cerium, praseodymiun, neodymium, promethum, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, lutetium and mixtures thereof.
- Preferred antimicrobial agents for use herein are the broad spectrum actives selected from the group consisting of Triclosan®, Triclocarban®, Octopirox®, PCMX, ZPT, natural essential oils and their key ingredients, and mixtures thereof.
- the most preferred antimicrobial active for use in the present invention is Triclosan®.
- the leave-on antimicrobial composition of the present invention comprise from 0.05% to 10, preferably from 0J to 2%, and more preferably from 0.2% to 1%, by weight of the leave-on composition, of an anionic surfactant.
- an anionic surfactant disrupts the lipid in the cell membrane of the bacteria.
- the particular acid used herein reduces the negative charges on the cell wall of the bacteria, crosses through the cell membrane, weakened by the surfactant, and acidifies the cytoplasm of the bacteria. The antimicrobial active can then pass more easily through the weakened cell wall, and more efficiently poison the bacteria.
- anionic lathering surfactants useful in the compositions of the present invention are disclosed in McCutcheon's, Detergents and Emulsifiers, North American edition (1990), published by The Manufacturing Confectioner Publishing Co.; McCutcheon's, Functional Materials. North American Edition (1992); and U.S. Patent No. 3,929,678, to Laughlin et al., issued December 30, 1975, all of which are incorporated by reference.
- anionic lathering surfactants include those selected from the group consisting of alkyl and alkyl ether sulfates, sulfated monoglycerides, sulfonated olefins, alkyl aryl sulfonates, primary or secondary alkane sulfonates, alkyl sulfosuccinates, acyl taurates, acyl isethionates, alkyl glycerylether sulfonate, sulfonated methyl esters, sulfonated fatty acids, alkyl phosphates, acyl glutamates, acyl sarcosinates, alkyl sulfoacetates, acylated peptides, alkyl ether carboxylates, acyl lactylates, anionic fluorosurfactants, and mixtures thereof.
- anionic lathering surfactants include those selected from the group consisting of alkyl and alky
- Anionic surfactants for use in the leave-on compositions include alkyl and alkyl ether sulfates. These materials have the respective formulae RIO-SO3M and R ⁇ (CH2H4 ⁇ ) x -
- O-SO3M wherein R! is a saturated or unsaturated, branched or unbranched alkyl group from 8 to 24 carbon atoms, x is 1 to 10, and M is a water-soluble cation such as ammonium, sodium, potassium, magnesium, triethanolamine, diethanolamine and monoethanolamine.
- the alkyl sulfates are typically made by the sulfation of monohydric alcohols (having from 8 to 24 carbon atoms) using sulfur trioxide or other known sulfation technique.
- the alkyl ether sulfates are typically made as condensation products of ethylene oxide and monohydric alcohols (having from 8 to 24 carbon atoms) and then sulfated.
- alkyl sulfates which may be used in the cleanser compositions are sodium, ammonium, potassium, magnesium, or TEA salts of lauryl or myristyl sulfate.
- alkyl ether sulfates which may be used include ammonium, sodium, magnesium, or TEA laureth-3 sulfate.
- sulfated monoglycerides of the form R 1 CO-0-CH2-C(OH)H-CH2-0-SO3M, wherein R 1 is a saturated or unsaturated, branched or unbranched alkyl group from 8 to 24 carbon atoms, and M is a water-soluble cation such as ammonium, sodium, potassium, magnesium, triethanolamine, diethanolamine and monoethanolamine.
- R 1 is a saturated or unsaturated, branched or unbranched alkyl group from 8 to 24 carbon atoms
- M is a water-soluble cation such as ammonium, sodium, potassium, magnesium, triethanolamine, diethanolamine and monoethanolamine.
- fatty acids having from 8 to 24 carbon atoms
- An example of a sulfated monoglyceride is sodium cocomonoglyceride sulfate.
- Suitable anionic surfactants include olefin sulfonates of the form RISO3M, wherein R! is a mono-olefin having from 12 to 24 carbon atoms, and M is a water-soluble cation such as ammonium, sodium, potassium, magnesium, triethanolamine, diethanolamine and monoethanolamine.
- R! is a mono-olefin having from 12 to 24 carbon atoms
- M is a water-soluble cation such as ammonium, sodium, potassium, magnesium, triethanolamine, diethanolamine and monoethanolamine.
- R! is a mono-olefin having from 12 to 24 carbon atoms
- M is a water-soluble cation such as ammonium, sodium, potassium, magnesium, triethanolamine, diethanolamine and monoethanolamine.
- R! is a mono-olefin having from 12 to 24 carbon atoms
- M is a water-soluble cation such as ammonium, sodium, potassium, magnesium, triethanolamine, diethanol
- anionic surfactants are the linear alkylbenzene sulfonates of the form R ⁇ " C6H4-SO3M, wherein R s a saturated or unsaturated, branched or unbranched alkyl group from 8 to 24 carbon atoms, and M is a water-soluble cation such as ammonium, sodium, potassium, magnesium, triethanolamine, diethanolamine and monoethanolamine. These are formed by the sulfonation of linear alkyl benzene with sulfur trioxide.
- An example of this anionic surfactant is sodium dodecylbenzene sulfonate.
- Still other anionic surfactants suitable for this leave-on composition include the primary or secondary alkane sulfonates of the form RISO3M, wherein R* is a saturated or unsaturated, branched or unbranched alkyl chain from 8 to 24 carbon atoms, and M is a water-soluble cation such as ammonium, sodium, potassium, magnesium, triethanolamine, diethanolamine and monoethanolamine.
- R* is a saturated or unsaturated, branched or unbranched alkyl chain from 8 to 24 carbon atoms
- M is a water-soluble cation such as ammonium, sodium, potassium, magnesium, triethanolamine, diethanolamine and monoethanolamine.
- R* is a saturated or unsaturated, branched or unbranched alkyl chain from 8 to 24 carbon atoms
- M is a water-soluble cation such as ammonium, sodium, potassium, magnesium, triethanolamine, diethanolamine and monoethanolamine.
- alkyl sulfosuccinates which include disodium N-octadecylsulfosuccinamate; diammonium lauryl sulfosuccinate; tetrasodium N-( 1 ,2- dicarboxyethyl)-N-octadecylsulfosuccinate; diamyl ester of sodium sulfosuccinic acid; dihexyl ester of sodium sulfosuccinic acid; and dioctyl esters of sodium sulfosuccinic acid.
- taurates which are based on taurine, which is also known as 2- aminoethanesulfonic acid.
- taurates include N-alkyltaurines such as the one prepared by reacting dodecylamine with sodium isethionate according to the teaching of U.S. Patent 2,658,072 which is incorporated herein by reference in its entirety.
- Other examples based of taurine include the acyl taurines formed by the reaction of n-methyl taurine with fatty acids (having from 8 to 24 carbon atoms).
- acyl isethionates Another class of anionic surfactants suitable for use in the leave-on composition are the acyl isethionates.
- the acyl isethionates typically have the formula RICO-O-CH2CH2SO3M wherein R* is a saturated or unsaturated, branched or unbranched alkyl group having from 10 to 30 carbon atoms, and M is a cation. These are typically formed by the reaction of fatty acids (having from 8 to 30 carbon atoms) with an alkali metal isethionate.
- Nonlimiting examples of these acyl isethionates include ammonium cocoyl isethionate, sodium cocoyl isethionate, sodium lauroyl isethionate, and mixtures thereof.
- alkylglyceryl ether sulfonates of the form R'-OCH2-C(OH)H-CH2"S ⁇ 3M, wherein R is a saturated or unsaturated, branched or unbranched alkyl group from 8 to 24 carbon atoms, and M is a water-soluble cation such as ammonium, sodium, potassium, magnesium, triethanolamine, diethanolamine and monoethanolamine.
- R is a saturated or unsaturated, branched or unbranched alkyl group from 8 to 24 carbon atoms
- M is a water-soluble cation such as ammonium, sodium, potassium, magnesium, triethanolamine, diethanolamine and monoethanolamine.
- R is a saturated or unsaturated, branched or unbranched alkyl group from 8 to 24 carbon atoms
- M is a water-soluble cation such as ammonium, sodium, potassium, magnesium, triethanolamine, diethanolamine and monoethanolamine.
- R is a saturated or unsaturated, branched
- R 1 is a saturated or unsaturated, branched or unbranched alkyl group from 8 to 24 carbon atoms.
- R 1 is a saturated or unsaturated, branched or unbranched alkyl group from 8 to 24 carbon atoms.
- R 1 is a saturated or unsaturated, branched or unbranched alkyl group from 8 to 24 carbon atoms.
- These can be formed by the sulfonation of fatty acids or alkyl methyl esters (having from 8 to 24 carbon atoms) with sulfiir trioxide or by another known sulfonation technique. Examples include alpha sulphonated coconut fatty acid and lauryl methyl ester.
- anionic materials include phosphates such as monoalkyl, dialkyl, and trialkylphosphate salts formed by the reaction of phosphorous pentoxide with monohydric branched or unbranched alcohols having from 8 to 24 carbon atoms. These could also be formed by other known phosphation methods.
- An example from this class of surfactants is sodium mono or dilaurylphosphate.
- anionic materials include acyl glutamates corresponding to the formula RlCO- N(COOH)-CH2CH2-C ⁇ 2M wherein R ⁇ is a saturated or unsaturated, branched or unbranched alkyl or alkenyl group of 8 to 24 carbon atoms, and M is a water-soluble cation.
- R ⁇ is a saturated or unsaturated, branched or unbranched alkyl or alkenyl group of 8 to 24 carbon atoms
- M is a water-soluble cation.
- anionic materials include alkanoyl sarcosinates corresponding to the formula R-*CON(CH3)-CH2CH2-C ⁇ 2M wherein R-' is a saturated or unsaturated, branched or unbranched alkyl or alkenyl group of 10 to 20 carbon atoms, and M is a water-soluble cation.
- R-' is a saturated or unsaturated, branched or unbranched alkyl or alkenyl group of 10 to 20 carbon atoms
- M is a water-soluble cation.
- anionic materials include alkyl ether carboxylates corresponding to the formula R ⁇ " (OCH2CH2) ⁇ -OCH2-C ⁇ 2M wherein R is a saturated or unsaturated, branched or unbranched alkyl or alkenyl group of 8 to 24 carbon atoms, x is 1 to 10, and M is a water-soluble cation.
- R is a saturated or unsaturated, branched or unbranched alkyl or alkenyl group of 8 to 24 carbon atoms
- x is 1 to 10
- M is a water-soluble cation.
- anionic materials include acyl lactylates corresponding to the formula RlCO-[O- CH(CH3)-CO] x -C ⁇ 2M wherein R* is a saturated or unsaturated, branched or unbranched alkyl or alkenyl group of 8 to 24 carbon atoms, x is 3, and M is a water-soluble cation.
- R* is a saturated or unsaturated, branched or unbranched alkyl or alkenyl group of 8 to 24 carbon atoms
- x is 3
- M is a water-soluble cation.
- anionic materials include the carboxylates, nonlimiting examples of which include sodium lauroyl carboxylate, sodium cocoyl carboxylate, and ammonium lauroyl carboxylate.
- Anionic flourosurfactants can also be used.
- the chain length of the anionic surfactant of the present invention can range from 8 to 24 carbon atoms, preferably from 10 to 18 carbon atoms and most preferably from 12 to 16 carbon atoms. Without being limited by theory, it is believed that surfactants with a chain length of 12 to 16 optimally interact with the biology of the cell membrane.
- Any counter cation, M can be used on the anionic surfactant.
- the counter cation is selected from the group consisting of sodium, potassium, ammonium, monoethanolamine, diethanolamine, and triethanolamine. More preferably the counter cation is ammonium.
- the biological activity of a surfactant and the mildness of a surfactant are inversely proportional; the higher the biological activity of the surfactant, the harsher the surfactant and the lower the biological activity of the surfactant, the milder the surfactant. Whether a biologically active, but harsh surfactant or a mild, but biologically inactive surfactant is desired will, of course, depend on (or influence) the selection of the other components.
- the biological activity/mildness of a pure surfactant can measured directly via a Microtox Response Test hereinafter described in the Analytical Methods section and can be reported as a Microtox Response Index.
- pure surfactant it is meant a chemical composition consisting essentially of a single surfactant entity, wherein the entity has essentially one chain length, head group and salt counter ion. From a standpoint of high biological activity, preferred anionic surfactants of the leave-on antimicrobial compositions of the present invention have a Microtox Response Index of less that 150, more preferably less than 100 and most preferably less than 50.
- preferred anionic surfactants of the leave-on antimicrobial compositions of the present invention have a Microtox Response Index of greater than 25, more preferably greater than 50 and most preferably greater than 100.
- Surfactants with a Microtox Response Index ranging from 25 to 150 are typically moderately biologically active and moderately mild.
- the Microtox Response Index for any individual surfactant component is not a reliable measurement of biological activity or mildness.
- the Microtox Index of each individual component can be determined and the weighted average used as the Index for the mixture if all the individual components of the mixture are known. If the individual components of a mixture are not known, then the primary head group and chain lengths of the surfactant mixture are better indicators of biological activity/mildness.
- the head group of the anionic surfactant be less than 15 Angstroms, preferably less than 10 Angstoms, and more preferably less than 7 Angstoms.
- the "head group” is defined as the hydrophilic portion (non- hydrocarbon) of the anionic surfactant, measured from the first polar atom to the end of the molecule.
- the head group size is estimated from the Van der Waals radius of the atoms and the configuration of the surfactant molecule. Head groups with sizes less than 7 Angstroms include sulfates, sulfonates, and phosphates. From the standpoint of mildness, it is preferred that the head group size is greater than 7 Angstoms, and preferably greater than 10 Angstoms.
- Head groups with sizes greater than 10 Angstroms include ethoxylated sulfates, glyceryl ether sulfonates, and isethionates. It is believed that as the head group size increases, more stearic hindrance at the cell wall prevents disruption by the surfactant and, thus, biological activity is decreased and mildness is increased.
- the mildness of a surfactant or mixture of surfactants can also be determined by a number of other known, conventional methods for measuring surfactant mildness.
- the Barrier Destruction Test set forth in T. J. Franz, J. Invest. Dermatol.. 1975, 64, pp. 190-195 and in U.S. Patent 4,673,525 to Small et al; issued June 16, 1987, both of which are herein incorporated by reference is a way of measuring mildness of surfactants.
- the milder the surfactant the less skin barrier that is destroyed in the barrier destruction test. Skin barrier destruction is measured by relative amount of radiolabeled water which passes from the test solution through the skin epidermis into the physiological buffer contained in the diffusate chamber.
- Surfactants having a Relative Skin Barrier Penetration Value of as close to zero as possible up to 75 are considered mild for purposes herein.
- Surfactants having a Relative Skin Barrier Penetration Value of greater than 75 are considered harsh for purposes herein.
- compositions comprising ALS are capable of providing very effective residual antibacterial effectiveness due to its activity, even with lower levels of antibacterial active and proton donating agent.
- compositions containing ALS may require the addition of co- surfactants or polymers, described herein in the Optional Ingredient Section, to achieve most preferred mildness levels for the present invention.
- ammonium laureth-3 sulfate 120
- ammonium laureth-3 sulfate 120
- Paraffin sulfonate a commercial grade surfactant sold under the name Hastapur SAS® from Hoechst Celanese, with a small head group and average chain length of 15.5 is a relatively active surfactant.
- Compositions comprising lower levels of active and acid can be used with higher levels of paraffin sulfonate, where the surfactant provides a larger component of residual effectiveness. Alternately, compositions comprising lower levels of paraffin sulfonate can be combined with even higher levels of active to achieve a mild and effective composition.
- Nonlimiting examples of preferred anionic surfactants useful herein include those selected from the group consisting of sodium and ammonium alkyl sulfates and ether sulfates having chain lengths of predominantly 12 and 14 carbon atoms, olefin sulfates having chain lengths of predominantly 14 and 16 carbon atoms, and paraffin sulfonates having chain lengths of from 13 to 17 carbon atoms, and mixtures thereof.
- ammonium and sodium lauryl sulfate ammonium and sodium myristyl sulfate, ammonium and sodium laureth-1 to laureth-4 sulfate, C14-C16 olefin sulfonates, C13-C17 paraffin sulfonates, and mixtures thereof.
- Non-anionic surfactants of the group consisting of nonionic surfactants, cationic surfactants, amphoteric surfactants and mixtures thereof, have been found to actually inhibit residual effectiveness benefits. It is believed that these surfactants interfere with the anionic surfactant disruption of the lipid in the cell membrane.
- the ratio of the amount of these non- anionic surfactants to the amount of anionic surfactant should be less than 1 :1, preferably less than 1 :2, and more preferably less than 1 :4.
- the leave-on antimicrobial compositions of the present invention preferably do not comprise hydrotropic sulfonates, particularly salts of terpenoids, or mono- or binuclear aromatic compounds such as sulfonates of camphor, toluene, xylene, cumene and naphthene.
- hydrotropic sulfonates particularly salts of terpenoids, or mono- or binuclear aromatic compounds such as sulfonates of camphor, toluene, xylene, cumene and naphthene.
- the leave-on antimicrobial composition of the present invention comprise from 0.1% to 10%, preferably from 0.5%) to 8%, more preferably from 1% to 5%, based on the weight of the leave-on composition, of a proton donating agent.
- proton donating agent it is meant any acid compound or mixture thereof, which results in undissociated acid on the skin after use.
- Proton donating agents can be organic acids, including polymeric acids, mineral acids or mixtures thereof.
- Proton donating agents which are organic acids which remain at least partially undissociated in the neat composition. These organic proton donating agents can be added directly to the composition in the acid form or can be formed by adding the conjugate base of the desired acid and a sufficient amount of a separate acid strong enough to form the undissociated acid from the base. Buffering Capacity
- Preferred organic proton donating agents are selected and formulated based on their buffer capacity and pKa.
- Buffer capacity is defined as the amount of protons (weight %) available in the formulation at the product pH for those acid groups with pKa's less than 6.0.
- Buffer capacity can be either calculated using pKa's, pH, and the concentrations of the acids and conjugate bases, ignoring any pKa greater than 6.0, or it can be determined experimentally through a simple acid-base titration using sodium hydroxide or potassium hydroxide using an endpoint of pH equals 6.0.
- Preferred organic proton donating agents of the antibacterial composition herein have a buffer capacity of greater than 0.005%, more preferably greater than 0.01%, even more preferably greater than 0.02%, and most preferably greater than 0.04%.
- Proton donating agents which are mineral acids will not remain undissociated in the neat composition .
- mineral acids can be effective proton donating agents for use herein. Without being limited by theory, it is believed that the strong mineral acid, acidify the carboxylic and phosphatidyl groups in proteins of the skin cells, thereby providing in-situ undissociated acid. These proton donating agents can only be added directly to the composition in the acid form. pH
- the pH of the leave-on antimicrobial compositions of the present invention must be adjusted to a sufficiently low level in order to either form or deposit substantial undissociated acid on the skin.
- the pH of the compositions should be adjusted and preferably buffered to range from 3.0 to 6.0, preferably from 3.0 to 5.0 and more preferably from 3.5 to 4.5.
- a non-exclusive list of examples of organic acids which can be used as the proton donating agent are adipic acid, tartaric acid, citric acid, maleic acid, malic acid, succinic acid, glycolic acid, glutaric acid, benzoic acid, malonic acid, salicylic acid, gluconic acid, polymeric acids, their salts, and mixtures thereof.
- a non-exclusive list of examples of mineral acid for use herein are hydrochloric, phosphoric, sulfuric and mixtures thereof.
- Polymeric acids are especially preferred acids for use herein from the standpoint that they cause less stinging to the skin than other acids.
- polymeric acid refers to an acid with repeating units of carboxylic acid groups joined together into one chain. Suitable polymeric acids can include homopolymers, copolymers and terpolymers, but must contain at least 30 mole% carboxylic acid groups.
- suitable polymeric acids useful herein include poly(acrylic) acid and its copolymers, both ionic and nonionic, (e.g., maleic-acrylic, sulfonic-acrylic, and styrene-acrylic copolymers), those cross-linked poly(acrylic) acids having a molecular weight of less than 250,000, preferably less than 100,000 poly ( ⁇ -hydroxy) acids, poly (methacrylic) acid, and naturally occurring polymeric acids such as carageenic acid, carboxy methyl cellulose, and alginic acid.
- Straight-chain poly(acrylic) acids are especially preferred for use herein. Water
- the leave-on antimicrobial compositions of the present invention comprise from 0% to 99.85%), preferably from 3% to 98%, more preferably from 5% to 97.5%, and most preferably from 38% to 95.99% water.
- Leave-on antimicrobial compositions of the present invention preferably have an apparent or neat viscosity of from 500 cps to 60,000 cps at 26J°C, preferably 5,000 to 30,000 cps.
- viscosity as used herein means the viscosity as measured by a Brookfield RVTDCP with a spindle CP-41 at 1 RPM for 3 minutes, unless otherwise specified.
- the "neat” viscosity is the viscosity of the undiluted liquid cleanser.
- ingredients to enhance the mildness to the skin can be added.
- these ingredients include cationic and nonionic polymers, co-surfactants, moisturizers and mixtures thereof.
- Polymers useful herein include polyethylene glycols, polypropylene glycols, hydrolyzed silk proteins, hydrolyzed milk proteins, hydrolyzed keratin proteins, guar hydroxypropyltrimonium chloride, polyquats, silicone polymers and mixtures thereof.
- the mildness enhancing polymers comprise from 0.1% to 1%, preferably from 0.2% to 1.0%, and more preferably from 0.2% to 0.6%, by weight of the leave-on antimicrobial composition, of the composition.
- Co-surfactants useful herein include nonionic surfactants such as the Genapol® 24 series of ethoxylated alcohols, POE(20) sorbitan monooleate (Tween® 80), polyethylene glycol cocoate and Pluronic® propylene oxide/ethylene oxide block polymers, and amphoteric surfactants such as alkyl betaines, alkyl sultaines, alkyl amphoacetates, alkyl amphodiacetates, alkyl amphopropionates, and alkyl amphodipropionates.
- the mildness enhancing cosurfactants comprise from 20% to 70%), preferably from 20% to 50%, by weight of the anionic surfactant, of the leave-on composition.
- lipid skin moisturizing agents which provide a moisturizing benefit to the user of the leave-on composition when the lipophilic skin moisturizing agent is deposited to the user's skin.
- lipophilic skin moisturizing agents When used in the antimicrobial leave-on compositions herein, lipophilic skin moisturizing agents are used, they are employed at a level of 0.1% to 30%, preferably from 0.2% to 10%, most preferably from 0.5% to 5% by weight of the composition.
- the lipophilic skin moisturizing agent can desirably be defined in terms of its solubility parameter, as defined by Vaughan in Cosmetics and Toiletries, Vol. 103, p. 47-69, October 1988.
- a lipophilic skin moisturizing agent having a Vaughan solubility Parameter (VSP) from 5 to 10, preferably from 5.5 to 9 is suitable for use in the leave-on antimicrobial compositions herein.
- VSP Vaughan solubility Parameter
- the lipophilic skin conditioning agent is selected from the group consisting of hydrocarbon oils and waxes, silicones, fatty acid derivatives, cholesterol, cholesterol derivatives, di and tri-glycerides, vegetable oils, vegetable oil derivatives, liquid nondigestible oils such as those described in U.S. Patents 3,600,186 to Mattson; Issued August 17, 1971 and 4,005,195 and 4,005,196 to Jandacek et al; both issued January 25, 1977, all of which are herein incorporated by reference, or blends of liquid digestible or nondigestible oils with solid polyol polyesters such as those described in U.S.
- Fatty acids, fatty acid soaps and water soluble polyols are specifically excluded from our definition of a lipophilic skin moisturizing agent.
- Hydrocarbon oils and waxes Some examples are petrolatum, mineral oil micro- crystalline waxes, polyalkenes (e.g. hydrogenated and nonhydrogenated polybutene and polydecene), paraffins, cerasin, ozokerite, polyethylene and perhydrosqualene. Blends of petrolatum and hydrogenated and nonhydrogenated high molecular weight polybutenes wherein the ratio of petrolatum to polybutene ranges from 90:10 to 40:60 are also suitable for use as the lipid skin moisturizing agent in the compositions herein.
- Silicone Oils Some examples are dimethicone copolyol, dimethylpolysiloxane, diethylpolysiloxane, high molecular weight dimethicone, mixed C1-C30 alkyl polysiloxane, phenyl dimethicone, dimethiconol, and mixtures thereof. More preferred are non-volatile silicones selected from dimethicone, dimethiconol, mixed C1-C30 alkyl polysiloxane, and mixtures thereof. Nonlimiting examples of silicones useful herein are described in U.S. Patent No. 5,011,681, to Ciotti et al., issued April 30, 1991, which is incorporated by reference.
- Di and tri-glycerides Some examples are castor oil, soy bean oil, derivatized soybean oils such as maleated soy bean oil, safflower oil, cotton seed oil, corn oil, walnut oil, peanut oil, olive oil, cod liver oil, almond oil, avocado oil, palm oil and sesame oil, vegetable oils and vegetable oil derivatives; coconut oil and derivatized coconut oil, cottonseed oil and derivatized cottonseed oil, jojoba oil, cocoa butter, and the like.
- soy bean oil soy bean oil, derivatized soybean oils such as maleated soy bean oil, safflower oil, cotton seed oil, corn oil, walnut oil, peanut oil, olive oil, cod liver oil, almond oil, avocado oil, palm oil and sesame oil, vegetable oils and vegetable oil derivatives
- coconut oil and derivatized coconut oil, cottonseed oil and derivatized cottonseed oil jojoba oil, cocoa butter, and the like.
- Acetoglyceride esters are used and an example is acetylated monoglycerides.
- Lanolin and its derivatives are preferred and some examples are lanolin, lanolin oil, lanolin wax, lanolin alcohols, lanolin fatty acids, isopropyl lanolate, acetylated lanolin, acetylated lanolin alcohols, lanolin alcohol linoleate, lanolin alcohol riconoleate.
- the lipophilic skin conditioning agent is comprised of lipids selected from the group consisting: petrolatum, blends of petrolatum and high molecular weight polybutene, mineral oil, liquid nondigestible oils (e.g. liquid cottonseed sucrose octaesters) or blends of liquid digestible or nondigestible oils with solid polyol polyesters (e.g.
- sucrose octaesters prepared from C22 fatty acids wherein the ratio of liquid digestible or nondigestible oil to solid polyol polyester ranges from 96:4 to 80:20, hydrogenated or nonhydrogenated polybutene, micro-crystalline wax, polyalkene, paraffin, cerasin, ozokerite, polyethylene, perhydrosqualene, dimethicones, alkyl siloxane, polymethylsiloxane, methylphenylpolysiloxane, and mixtures thereof.
- the ratio of petrolatum to the other selected lipids is preferably from 10:1 to 1:2, more preferably from 5:1 to 1 :1.
- a stabilizer may also be included at a level ranging from 0.1% to 10%, preferably from 0.1% to 8%, more preferably from 0.1% to 5% by weight of the leave-on antimicrobial composition.
- the stabilizer is used to form a crystalline stabilizing network in the leave-on composition that prevents the lipophilic skin moisturizer agent droplets from coalescing and phase splitting in the product.
- the network exhibits time dependent recovery of viscosity after shearing (e.g., thixotropy).
- the stabilizers used herein are not surfactants.
- the stabilizers provide improved shelf and stress stability.
- Some preferred hydroxyl-containing stabilizers include 12-hydroxystearic acid, 9J O-dihydroxystearic acid, tri-9J O-dihydroxystearin and tri- 12-hydroxystearin (hydrogenated castor oil is mostly tri-12-hydroxystearin). Tri-12-hydroxystearin is most preferred for use in the compositions herein.
- hydroxyl-containing stabilizers When these crystalline, hydroxyl-containing stabilizers are utilized in the leave-on compositions herein, they are typically present at from 0.1% to 10%, preferably from 0.1%) to 8%, more preferably from 0.1% to 5% of the leave-on antimicrobial compositions.
- the stabilizer is insoluble in water under ambient to near ambient conditions.
- the stabilizer employed in the leave-on compositions herein can comprise a polymeric thickener.
- polymeric thickeners as the stabilizer in the leave-on compositions herein they are typically included in an amount ranging from 0.01% to 5%, preferably from 0.3% to 3%, by weight of the composition.
- the polymeric thickener is preferably an anionic, nonionic, cationic or hydrophobically modifier polymer selected from the group consisting of cationic polysaccharides of the cationic guar gum class with molecular weights of 1,000 to 3,000,000, anionic, cationic, and nonionic homopolymers derived from acrylic and/or methacrylic acid, anionic, cationic, and nonionic cellulose resins, cationic copolymers of dimethyldialkylammonium chloride, and acrylic acid, cationic homopolymers of dimethylalkylammonium chloride, cationic polyalklene, and ethoxypolyalkylene imines, polyethylene glycol of molecular weight from 100,000 to 4,000,000, and mixtures thereof.
- the polymer is selected from the group consisting of sodium polyacrylate, hydroxy ethyl cellulose, cetyl hydroxy ethyl cellulose, and Polyquaternium 10.
- the stabilizer employed in the leave-on compositions herein can comprise C10-C22 ethylene glycol fatty acid esters.
- C10-C22 ethylene glycol fatty acid esters can also desirably be employed in combination with the polymeric thickeners hereinbefore described.
- the ester is preferably a diester, more preferably a C14-C18 diester, most preferably ethylene glycol distearate.
- C 10-C22 ethylene glycol fatty acid esters are utilized as the stabilizer in the leave-on compositions herein, they are typically present at from 3% to 10%, preferably from 5% to 8%, more preferably from 6% to 8% of the leave-on compositions.
- Another class of stabilizer which can be employed in the leave-on antimicrobial compositions of the present invention comprises dispersed amorphous silica selected from the group consisting of filmed silica and precipitated silica and mixtures thereof.
- dispersed amorphous silica refers to small, finely divided non-crystalline silica having a mean agglomerate particle size of less than 100 microns.
- Fumed silica which is also known as arced silica, is produced by the vapor phase hydrolysis of silicon tetrachloride in a hydrogen oxygen flame. It is believed that the combustion process creates silicone dioxide molecules which condense to form particles. The particles collide, attach and sinter together. The result of this process is a three dimensional branched chain aggregate. Once the aggregate cools below the fusion point of silica, which is 1710°C, further collisions result in mechanical entanglement of the chains to form agglomerates. Precipitated silicas and silica gels are generally made in aqueous solution.
- the fumed silica preferably has a mean agglomerate particle size ranging from 0J microns to 100 microns, preferably from 1 micron to 50 microns, and more preferably from 10 microns to 30 microns.
- the agglomerates are composed of aggregates which have a mean particle size ranging from 0.01 microns to 15 microns, preferably from 0.05 microns to 10 microns, more preferably from 0J microns to 5 microns and most preferably from 0.2 microns to 0.3 microns.
- the silica preferably has a surface area greater than 50 sq. m/gram, more preferably greater than 130 sq. m./gram, most preferably greater than 180 sq. m./gram.
- amorphous silicas When amorphous silicas are used as the stabilizer herein, they are typically included in the leave-on compositions at levels ranging from 0.1% to 10%, preferably from 0.25%) to 8%, more preferably from 0.5% to 5%.
- a fourth class of stabilizer which can be employed in the leave-on antimicrobial compositions of the present invention comprises dispersed smectite clay selected from the group consisting of bentonite and hectorite and mixtures thereof.
- Bentonite is a colloidal aluminum clay sulfate. See Merck Index, Eleventh Edition, 1989, entry 1062, p. 164, which is incorporated by reference.
- Hectorite is a clay containing sodium, magnesium, lithium, silicon, oxygen, hydrogen and flourine. See Merck Index, eleventh Edition, 1989, entry 4538, p. 729, which is herein incorporated by reference.
- smectite clay When smectite clay is employed as the stabilizer in the leave-on compositions of the present invention, it is typically included in amounts ranging from 0.1% to 10%, preferably from 0.25% to 8%, more preferably from 0.5% to 5%>.
- compositions of the present invention can comprise a wide range of optional ingredients.
- Nonlimiting examples of functional classes of ingredients are described at page 537 of this reference.
- Examples of these functional classes include: abrasives, anti-acne agents, anticaking agents, antioxidants, binders, biological additives, bulking agents, chelating agents, chemical additives, colorants, cosmetic astringents, cosmetic biocides, denaturants, drug astringents, emulsifiers, external analgesics, film formers, fragrance components, humectants, opacifying agents, plasticizers, preservatives, propellants, reducing agents, skin bleaching agents, skin-conditioning agents (emollient, humectants, miscellaneous, and occlusive), skin protectants, solvents, foam boosters, hydrotropes, solubilizing agents, suspending agents (nonsurfactant), sunscreen agents, ultraviolet light absorbers, and viscosity increasing agents (aqueous and nonaqueous).
- Examples of other functional classes of materials useful herein that are well known to one of ordinary skill in the art include solubilizing agents, sequestrants,
- the leave-on antimicrobial compositions herein have the following characteristics.
- the rinse of antimicrobial cleansing compositions of the present invention have one of three characteristics of bacterial effectiveness.
- the leave-on antimicrobial compositions of the present invention have a Gram Negative Residual Effectiveness Index of greater than about 0.3 (50%) reduction), preferably greater than about 1.0 (90% reduction), and more preferably greater than about 2.0 (99%) reduction).
- the Gram Negative Residual Effectiveness Index is measured by the In-Vivo Residual Effectiveness on Escherichia coli Test described hereinafter in the Analytical Methods Section.
- the index represents a difference in base ten logarithm values of bacterial concentrations between a test sample and a control.
- the leave-on antimicrobial compositions of the present invention comprise a Gram Positive Residual Effectiveness Index of greater than 0.5 (68% reduction), preferably greater than 1.0 (90.0% reduction), more preferably greater than 2.0 (99% reduction), and most preferably greater than 2.3 (99.5%> reduction).
- the Gram Positive Residual Effectiveness Index is measured by the In-Vivo Residual Effectiveness on Staphylococcus aureus Test described herein.
- the index represents a difference in base ten logarithm values of bacterial concentrations between a test sample and a placebo control.
- the leave-on antimicrobial compositions provide improved immediate germ reduction.
- the degree of reduction can be measured after one- wash (application) of the In-Vivo Health Care Personal Handwash Test described herein.
- the leave-on antimicrobial composition has One-wash Immediate Germ Reduction Index of greater than about 1.0 (90% reduction), preferably greater than about 1.5 (96.8% reduction), more preferably greater than about 2.0 (99%> reduction), and most preferably greater than about 2.3 (99.5% reduction).
- the index represents a difference in base ten logarithm values of bacterial concentrations between before and after washing.
- the leave-on antimicrobial compositions of the present invention comprise a Mildness Index of greater than 0.3, preferably greater than 0.4, and more preferably greater than 0.6.
- the Mildness Index is measured by the Forearm Controlled Application Test (FCAT) described herein.
- the leave-on antimicrobial compositions of the present invention are made via art recognized techniques for the various forms of leave-on products.
- the leave-on antimicrobial compositions of the present invention are useful for controlling the spread of Gram positive bacteria over time.
- a suitable or effective amount of the composition is applied to the area to be treated.
- a suitable amount of the cleansing composition can be applied via intermediate application to a washcloth, sponge, pad, cotton ball, puff or other application device.
- an effective amount of product to be used will depend upon the needs and usage habits of the individual.
- Typical amounts of the present compositions useful for cleansing range from 0J mg/cm ⁇ to 10 mg/cm ⁇ , preferably from 0.6 mg/crn ⁇ to 5 mg/cm ⁇ skin area to be cleansed.
- volume I-IV Microbics Corporation.
- the stock solution of the test anionic surfactant sample is prepared and used as a stock solution from which all other dilutions are made.
- the standard "starting concentration", the highest concentration to be tested, is 500 ppm. (If a 500 ppm starting concentration fails to give a calculable result, e.g. an active surfactant kills all reagent at all dilutions, the starting concentration can be adjusted based on a known range of EC50 values of previously tested surfactants.)
- the stock solution is prepared at two times the starting concentration. a) Add OJg (or adjusted amount if required) of anionic surfactant, accounting for activity of raw material, to beaker. b) Microtox Diluent (2% NaCl, Microbics Corp.) is added to total lOOg. c) Stir solution to make sure of adequate mixing.
- the concentration of test substance, in ppm, that decreases the bioluminescence of the Microtox Acute Toxicity Reagent by 50%) from the starting value (EC50 Value) can be calculated using the Run Statistics on Data File option of the Microtox Software (recommended) or by conducting a linear regression of the data (% reduction vs. log of concentration). % Reductions are calculated using the following formulas:
- the Microtox Index is the EC50 value in ppm.
- Residual Antibacterial efficacy of liquid and bar soap antimicrobial products are quantified in the following method. Reductions are reported from a control, non- antibacterial placebo soap, without further treatment, used on one of the subjects forearms. By definition the antibacterial placebo will show no residual effectiveness in the test.
- Subjects are instructed not to use antibacterial products for 7 days prior to testing. Immediately before test, the subjects hands are examined for cuts/broken skin that would preclude them from participating.
- E. coli inoculum (ATCC 10536, grown from lyophilized stock in Soybean-casein broth at 37C for 18-24 hrs) is adjusted to approximately 10 -* organisms/ml (0.45 transmittance vs. TSB blank on specrophotometer).
- Each test site is inoculated with 10 ⁇ l of E. coli. Inoculum is spread with inoculating loop into a ⁇ 3 cm ⁇ circle and covered with a Hilltop Chamber (Hilltop Research Inc.).
- This procedure is repeated for each test site on each forearm. 5.
- Sampling Bacteria (Extraction Procedure) a) Prepare sampling solution of 0.04% KH 2 P0 4 , 1.01% Na 2 HP0 , 0.1% Triton X- 100, 1.5% Polysorbate 80, 0.3% Lecithin in water, adjusted to pH 7.8 with 1 N HC1. b) Exactly 60 minutes after inoculation, the Hilltop Chamber is removed from the site from which a sample is to be taken. A 8.6 cm-2 sampling cup in placed over the site c) 5 ml of sampling solution is added to the cup. d) Extract the bacteria by gently rubbing site with glass police man for 30 seconds. e) Remove sampling solution with pipette and place in a sterile labeled test tube. f) Repeat extraction with 5 ml of sampling fluid. This entire extraction procedure is repeated for each site 60 minutes after inoculation.
- Gram Negative Residual Efficacy Index log jo (CFU's/ml of placebo site) - logjo (CFU's/ml of test product site)
- Test Design Residual Antibacterial efficacy of liquid and bar soap antimicrobial products are quantified in the following method. Reductions are reported from a control, non- antibacterial placebo soap, without further treatment, used on one of the subjects forearms. By definition the antibacterial placebo will show no residual effectiveness in the test.
- Subjects are instructed not to use antibacterial products for 7 days prior to testing. Immediately before test, the subjects hands are examined for cuts/broken skin that would preclude them from participating.
- S. aureus inoculum (ATCC 27217, grown from lyophilized stock in Soybean- casein broth at 37C for 18-24 hrs) is adjusted to approximately 10° organisms/ml (0.45 transmittance vs. TSB blank on specrophotometer).
- Each test site is inoculated with 10 ⁇ l of S. aureus. Inoculum is spread with inoculating loop into a ⁇ 3 cm-2 circle and covered with a Hilltop Chamber (Hilltop Research Inc.).
- This procedure is repeated for each test site on each forearm.
- Sampling Bacteria (Extraction Procedure) a) Prepare sampling solution of 0.04% KH 2 P0 4 , 1.01% Na HP0 4 , 0.1% Triton X- 100, 1.5% Polysorbate 80, 0.3% Lecithin in water, adjusted to pH 7.8 with 1 N HC1. b) Exactly 60 minutes after inoculation, the Hilltop Chamber is removed from the site from which a sample is to be taken. A 8.6 crcfi sampling cup in placed over the site. c) 5 ml of sampling solution is added to the cup. d) Extract the bacteria by gently rubbing site with glass police man for 30 seconds. e) Remove sampling solution with pipette and place in a sterile labeled test tube. f) Repeat extraction with 5 ml of sampling fluid. This entire extraction procedure is repeated for each site 60 minutes after inoculation.
- Gram Positive Residual Efficacy Index logjo (CFU's/ml of placebo site) - logj ⁇ (CFU's/ml of test product site)
- Organism Serratia marcescens ATCC 14756 (incubated 18-24 hrs. at 25C in soybean casein broth, adjusted to -10° organisms/ml by diluting to 0.45 transmittance with a spectrophotometer)
- Dilution Fluid phosphate buffer (0.1% Triton X-100, 00.3% Lecithin, 1.5% Tween 80) adjusted to pH 7.2 with 1 N HC1
- Agar Soybean casein agar with 1.5% polysorbate 80 d.
- test leave-on composition in subject's hand. Subject then spreads composition on hands, rubbing for thirty (30) seconds, covering palm, back of hand, fingers and web areas between fingers, cuticles, and nail beds. Hands are not dried, e. Bacteria were enumerated by performing serial dilutions (1 : 10) of inoculum or extracted samples and spreading 0J ml of dilution on plates. Results are reported as the log reduction of bacteria from baseline.
- the Forearm Controlled Application Test is a comparative test which discriminates differences in product mildness to the skin. A test product is compared to a standard soap based cleansing bar control. Test Group Restrictions
- Test groups of 20-30 subjects, 18 to 55 years of age, who regularly wash with soap are used. Potential subjects who (1) have an initial dryness grade of 3.0 or higher on the forearms as assessed during the initial examination, (2) have skin cancer, eczema, or psoriasis on the forearms, (3) are receiving injectable insulin, (4) are pregnant or lactating, or (5) are receiving treatment for skin problems or contact allergy are excluded. Subjects are to avoid hot tubs, swimming, and sun lamps, and to refrain from applying any soaps, cleansing products, creams, or gels to their forearms for the duration of the study. Subjects are to keep water off their forearms for at least two hours before the grading process. The studies are executed using a blinded, random product order format. Clinical assistant should verify the correct treatment sequence and document such before washing each subject.
- Products are applied to the forearms a total of nine (9) times: two (2) times each day on the first four (4) days of the study and one (1) time on the final day. Visits to the test facility for washing must be spaced by a minimum of three (3) hours.
- Control Product All clinical assistants must wear disposable gloves during wash procedure, rinsing them between treatments, and changing between subjects.
- the control product is a rolled bar soap containing: 56.1% Sodium Tallowate 18.7% Sodium Cocoate
- the subject wets the entire surface of his/her volar forearm with 95-100°F tap water by holding the arm briefly under running tap water.
- a clinical assistant wets one-quarter sheet (approximately 8" x 6") of Masslinn® towel with tap water, then squeezes the towel gently to remove excess water.
- a clinical assistant applies the products to the arm, beginning with the product designated for the site nearest the elbow, using the appropriate procedure as follows:
- Liquid Product a. Dispense 0J0 cc of test product from a syringe into the center of the appropriate marked area. b. Wet two finders of gloved (latex) hand under the running tap (index and middle fingers). c. Move wetted fingers in a circular motion over the application site for 10 seconds to lather product. d. Lather remains on the application site for 90 seconds, then is rinsed off with running tap water for 15 seconds, taking care not to wash lather off the adjacent sites. After 10 seconds of the rinse has expired, the Clinical Assistant will gently rub the site being rinsed with her two gloved fingers for the remaining 5 seconds of the rinse..
- Bar Product a. Wet two finders of gloved (latex) hand under the running tap (index and middle fingers). b. Wet bar by holding bar briefly under running tap water. Test bars must be wet under a running tap at the start of each day. c. Rub wetted fingers in a circular motion, over the surface of the bar, for 15 seconds to form lather on bar and fingers. d. Rub the lathered fingers on the application site in a circular motion for 10 seconds to lather product on the skin. e. Lather remains on the application site for 90 seconds, then is rinsed off with running tap water for 15 seconds, taking care not to wash lather off the adjacent sites.
- Wive Products a. Fold wipe in half, crosswise, and gently rub the wipe in a curricular motion within the appropriate area. b. Allow site to air dry for 90 seconds. Do not rinse site.
- Leave-on Product a. Dispense 0J0 cc of test product from a syringe into the center of the appropriate marked area. b. Move gloved fingers in a circular motion over the application site for 10 seconds. c. Allow site to air dry for 90 seconds. Do not rinse site.
- Steps 1-4 are repeated on the appropriate test areas so two applications of product are made to test areas.
- the clinical assistant gently pats the subject's arm dry with a disposable paper towel.
- the skin on each treatment area is evaluated by an expert grader at baseline and three hours after the final study wash.
- the treatment areas are evaluated under 2J5x magnification (model KFM-IA Luxo Illuminated Magnifying Lamp, Marshall Industries, Dayton, OH) with controlled lighting (General Electric Cool White, 22-watt, 8" Circuline fluorescent bulb).
- the skin is evaluated by an expert grader, for dryness and a rating is assigned based on the definitions set forth below.
- Rc 0 The average rating of control product area at baseline
- Rcf The average rating of control product area at test end
- Rt 0 The average rating of test product area at baseline
- Rtf The average rating if test product area at test end.
- the test is valid only if sufficient response is observed in the skin to the control product.
- the control response must be greater than 1.0 (i.e., Rcf - Rc 0 > 1.0) for the test to be valid.
- the Mildness Index of the test product is the difference in the skin responses to two products.
- the Carrimed CSL 100 Controlled Stress Rheometer is used to determine Shear Index, n, and Consistency, k, of the lipophilic skin moisturizing agent used herein. The determination is performed at 35°C with the 4 cm 2° cone measuring system typically set with a 51 micron gap and is performed via the programmed application of a shear stress (typically from 0.06 dynes/sq. cm to 5,000 dynes/sq. cm) over time. If this stress results in a deformation of the sample, i.e. strain of the measuring geometry of at least 10-4 rad/sec, then this rate of strain is reported as a shear rate. These data are used to create a viscosity ⁇ Vs.
- shear rate ⁇ ' flow curve for the material. This flow curve can then be modeled in order to provide a mathematical expression that describes the material's behavior within specific limits of shear stress and shear rate.
- the Wells-Brookfield Cone/Plate Model DV-II+ Viscometer is used to determine the viscosity of the leave-on antimicrobial compositions herein. The determination is performed at 25°C with the 2.4 cm° cone (Spindle CP-41) measuring system with a gap of 0.013 mm between the two small pins on the respective cone and plate. The measurement is performed by injecting 0.5 ml of the sample to be analyzed between the cone and plate and rotating the cone at a set speed of 1 rpm. The resistance to the rotation of the cone produces a torque that is proportional to the shear stress of the liquid sample. The amount of torque is read and computed by the viscometer into absolute centipoise units (mPa's) based on geometric constants of the cone, the rate of rotation, and the stress related torque.
- mPa's absolute centipoise units
- Ingredients are identified by chemical or CTFA name.
- Leave-on Antimicrobial compositions are prepared according to the tables below. Leave-on Antimicrobial Com ositions
- the leave-on antimicrobial compositions shown all have a Gram Negative Residual Effectiveness Index of greater than about 0.3, a Gram Positive Residual Effectiveness Index of greater than 0.5, have a One-wash Immediate Germ Reduction Index of greater than about 1.0; and a Mildness Index of greater than 0.3.
- Procedure for Making Leave-on Antimicrobial Composition Examples When mineral oil is used, premix mineral oil, propylene glycol, active, steareth 2 and 20, oleth 2 and 20, and 50%>, by weight of the oil, glycol, active, steareth and oleth materials, water to a premix vessel. Heat to 165°F ⁇ 10°F. Add additional 50%>, by weight of the oil, glycol, active, steareth and oleth materials, of water to the premix tank.
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- Dermatology (AREA)
- Epidemiology (AREA)
- Birds (AREA)
- Emergency Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Cosmetics (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Detergent Compositions (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU77048/98A AU745392B2 (en) | 1997-06-04 | 1998-05-29 | Mild, leave-on antimicrobial compositions |
JP50260799A JP2001518941A (ja) | 1997-06-04 | 1998-05-29 | マイルドなリーブオン抗菌性組成物 |
BR9811706-8A BR9811706A (pt) | 1997-06-04 | 1998-05-29 | Composições antimicrobianas brandas sem-remoção |
EP98925006A EP0996420A2 (fr) | 1997-06-04 | 1998-05-29 | Composition nettoyante liquide antimicrobienne douce a conserver |
CA002291249A CA2291249C (fr) | 1997-06-04 | 1998-05-29 | Composition nettoyante liquide antimicrobienne douce a conserver |
Applications Claiming Priority (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US86871897A | 1997-06-04 | 1997-06-04 | |
US86930397A | 1997-06-04 | 1997-06-04 | |
US86930197A | 1997-06-04 | 1997-06-04 | |
US08/869,301 | 1997-06-04 | ||
US08/869,303 | 1997-06-04 | ||
US08/868,718 | 1997-06-04 | ||
US08/967,972 | 1997-11-12 | ||
US08/967,972 US6287577B1 (en) | 1997-11-12 | 1997-11-12 | Leave-on antimicrobial compositions which provide improved residual benefit versus gram positive bacteria |
Publications (2)
Publication Number | Publication Date |
---|---|
WO1998055081A2 true WO1998055081A2 (fr) | 1998-12-10 |
WO1998055081A3 WO1998055081A3 (fr) | 1999-03-11 |
Family
ID=27505954
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1998/010978 WO1998055081A2 (fr) | 1997-06-04 | 1998-05-29 | Composition nettoyante liquide antimicrobienne douce a conserver |
Country Status (10)
Country | Link |
---|---|
EP (1) | EP0996420A2 (fr) |
JP (1) | JP2001518941A (fr) |
CN (1) | CN1265028A (fr) |
AR (1) | AR012240A1 (fr) |
AU (1) | AU745392B2 (fr) |
BR (1) | BR9811706A (fr) |
CA (1) | CA2291249C (fr) |
CO (1) | CO4940379A1 (fr) |
PE (1) | PE79499A1 (fr) |
WO (1) | WO1998055081A2 (fr) |
Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000061107A1 (fr) * | 1999-04-13 | 2000-10-19 | The Procter & Gamble Company | Chiffons antimicrobiens |
WO2000061106A1 (fr) * | 1999-04-13 | 2000-10-19 | The Procter & Gamble Company | Chiffons antimicrobiens presentant une meilleure reduction immediate de germes |
WO2000061105A1 (fr) * | 1999-04-13 | 2000-10-19 | The Procter & Gamble Company | Chiffons antimicrobiens |
WO2001053444A1 (fr) * | 2000-01-20 | 2001-07-26 | The Procter & Gamble Company | Compositions antimicrobiennes |
US6436885B2 (en) | 2000-01-20 | 2002-08-20 | The Procter & Gamble Company | Antimicrobial cleansing compositions containing 2-pyrrolidone-5-carboxylic acid |
EP1264589A1 (fr) * | 2001-06-07 | 2002-12-11 | L'oreal | Utilisation d'un additif polaire dans une composition cosmétique comprenant une phase grasse liquide structurée par au moins un organogelateur pour donner à la composition un caractére thixotrope |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6324781B2 (ja) * | 2014-03-19 | 2018-05-16 | 花王株式会社 | 殺菌洗浄剤組成物 |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4026756A1 (de) * | 1990-08-24 | 1992-02-27 | Turner Gmbh | Konservierungsmittel und deren verwendung |
WO1992018100A1 (fr) * | 1991-04-15 | 1992-10-29 | The Procter & Gamble Company | Nettoyant liquide, doux, antibacterien pour la peau |
WO1995003781A1 (fr) * | 1993-07-03 | 1995-02-09 | The Procter & Gamble Company | Composition de nettoyage destinees aux personnes |
WO1995024179A1 (fr) * | 1994-03-11 | 1995-09-14 | The Procter & Gamble Company | COMPOSITIONS COSMETIQUES HYDROLYTIQUEMENT STABLES, A pH BAS, CONTENANT DES INGREDIENTS ACTIFS ACIDES |
GB2288811A (en) * | 1994-04-26 | 1995-11-01 | Procter & Gamble | Cleansing compositions |
WO1995032705A1 (fr) * | 1994-06-01 | 1995-12-07 | Unilever Plc | Formulations nettoyantes liquides, antimicrobiennes et douces |
WO1997003647A1 (fr) * | 1995-07-24 | 1997-02-06 | The Procter & Gamble Company | Compositions topiques pour application locale a contact cutane plus confortable |
WO1997040816A1 (fr) * | 1996-05-02 | 1997-11-06 | The Procter & Gamble Company | Compositions topiques comportant un complexe de tensio-actifs disperses |
-
1998
- 1998-05-29 EP EP98925006A patent/EP0996420A2/fr not_active Withdrawn
- 1998-05-29 AU AU77048/98A patent/AU745392B2/en not_active Ceased
- 1998-05-29 BR BR9811706-8A patent/BR9811706A/pt not_active IP Right Cessation
- 1998-05-29 CA CA002291249A patent/CA2291249C/fr not_active Expired - Fee Related
- 1998-05-29 JP JP50260799A patent/JP2001518941A/ja not_active Ceased
- 1998-05-29 WO PCT/US1998/010978 patent/WO1998055081A2/fr not_active Application Discontinuation
- 1998-05-29 CN CN98807631A patent/CN1265028A/zh active Pending
- 1998-06-04 CO CO98031818A patent/CO4940379A1/es unknown
- 1998-06-04 PE PE1998000450A patent/PE79499A1/es not_active Application Discontinuation
- 1998-06-04 AR ARP980102626A patent/AR012240A1/es not_active Application Discontinuation
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4026756A1 (de) * | 1990-08-24 | 1992-02-27 | Turner Gmbh | Konservierungsmittel und deren verwendung |
WO1992018100A1 (fr) * | 1991-04-15 | 1992-10-29 | The Procter & Gamble Company | Nettoyant liquide, doux, antibacterien pour la peau |
WO1995003781A1 (fr) * | 1993-07-03 | 1995-02-09 | The Procter & Gamble Company | Composition de nettoyage destinees aux personnes |
WO1995024179A1 (fr) * | 1994-03-11 | 1995-09-14 | The Procter & Gamble Company | COMPOSITIONS COSMETIQUES HYDROLYTIQUEMENT STABLES, A pH BAS, CONTENANT DES INGREDIENTS ACTIFS ACIDES |
GB2288811A (en) * | 1994-04-26 | 1995-11-01 | Procter & Gamble | Cleansing compositions |
WO1995032705A1 (fr) * | 1994-06-01 | 1995-12-07 | Unilever Plc | Formulations nettoyantes liquides, antimicrobiennes et douces |
WO1997003647A1 (fr) * | 1995-07-24 | 1997-02-06 | The Procter & Gamble Company | Compositions topiques pour application locale a contact cutane plus confortable |
WO1997040816A1 (fr) * | 1996-05-02 | 1997-11-06 | The Procter & Gamble Company | Compositions topiques comportant un complexe de tensio-actifs disperses |
Non-Patent Citations (1)
Title |
---|
See also references of EP0996420A2 * |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000061107A1 (fr) * | 1999-04-13 | 2000-10-19 | The Procter & Gamble Company | Chiffons antimicrobiens |
WO2000061106A1 (fr) * | 1999-04-13 | 2000-10-19 | The Procter & Gamble Company | Chiffons antimicrobiens presentant une meilleure reduction immediate de germes |
WO2000061105A1 (fr) * | 1999-04-13 | 2000-10-19 | The Procter & Gamble Company | Chiffons antimicrobiens |
US6413529B1 (en) | 1999-04-13 | 2002-07-02 | The Procter & Gamble Company | Antimicrobial wipes which provide improved residual benefit versus gram negative bacteria |
US6482423B1 (en) | 1999-04-13 | 2002-11-19 | The Procter & Gamble Company | Antimicrobial wipes which provide improved residual benefit versus gram positive bacteria |
US6488943B1 (en) | 1999-04-13 | 2002-12-03 | The Procter & Gamble Company | Antimicrobial wipes which provide improved immediate germ reduction |
WO2001053444A1 (fr) * | 2000-01-20 | 2001-07-26 | The Procter & Gamble Company | Compositions antimicrobiennes |
US6436885B2 (en) | 2000-01-20 | 2002-08-20 | The Procter & Gamble Company | Antimicrobial cleansing compositions containing 2-pyrrolidone-5-carboxylic acid |
EP1264589A1 (fr) * | 2001-06-07 | 2002-12-11 | L'oreal | Utilisation d'un additif polaire dans une composition cosmétique comprenant une phase grasse liquide structurée par au moins un organogelateur pour donner à la composition un caractére thixotrope |
FR2825618A1 (fr) * | 2001-06-07 | 2002-12-13 | Oreal | Utilisation d'un additif polaire dans une composition cosmetique comprenant une phase grasse liquide structuree par au moins un organogelateur pour donner a la composition un caractere thixotrope |
Also Published As
Publication number | Publication date |
---|---|
AU7704898A (en) | 1998-12-21 |
PE79499A1 (es) | 1999-10-15 |
EP0996420A2 (fr) | 2000-05-03 |
AR012240A1 (es) | 2000-09-27 |
CO4940379A1 (es) | 2000-07-24 |
CA2291249A1 (fr) | 1998-12-10 |
BR9811706A (pt) | 2000-07-25 |
AU745392B2 (en) | 2002-03-21 |
WO1998055081A3 (fr) | 1999-03-11 |
JP2001518941A (ja) | 2001-10-16 |
CN1265028A (zh) | 2000-08-30 |
CA2291249C (fr) | 2004-03-02 |
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