Patent Application
20100261630
The present invention resides in the art of antimicrobial hand wash formulations. More particularly, the present invention relates to a highly efficacious antimicrobial hand wash containing relatively low levels of skin-irritating surfactants and active ingredients.
Most antimicrobial hand wash formulations exhibiting broad spectrum activity contain surfactants, active ingredients, or both. Surfactants are employed, in part, to help solubilize the active ingredients, and to make them useful in the formulation. The surfactants are typically selected from anionic, non-ionic, amphoteric, quaternary ammonium, and amine oxide surfactants. As is generally appreciated, all of these classes of surfactants have their positive and negative properties. For example, quaternary ammonium compounds are compatible with phenol-based active ingredients such as 2,3,4′-trichloro-2′-hydroxydiphenylether (triclosan), 2,2′-dihydroxy-5,5′-dibromodiphenyl ether, p-chloro-m-xylenol (pcmx), and ortho-phenylphenol, but, when they are used, the hand washes do not foam to a great extent. Amphoterics and amine oxides are expensive. Anionics and non-ionics also tend not to interact well with the active ingredients.
Active ingredients are typically selected from bisguanidines, quaternary ammonium compounds, benzyl alcohols, trihalocarbanilides, iodine-containing compounds, and phenol-based compounds. All of these types of active ingredients have found niches in today's cosmetic markets. The phenol-based actives, such as triclosan, 2,2′-dihydroxy-5,5′-dibromodiphenyl ether, pcmx, and ortho-phenylphenol are extensively used in hand wash formulations. But, despite their extensive use, there are numerous negative associations with using these as active agents. Owing to the non-polar character of these compounds, they are sparingly soluble in an aqueous environment. Solvents, such as propylene glycol, or hydrotropes, such as sodium xylene sulfonate, are often required to incorporate them into an aqueous hand wash system. The use of solvents and hydrotropes usually cause detrimental effects to the final hand wash either via an increased cost or increased irritancy. The aqueous environment might be heated in order to increase solubility and avoid the negative effects of the solvents and hydrotropes, but adding heat is undesirable because large amounts of energy and extended manufacturing times are required. A hand wash that is low in solids would offer the advantages of reduced cost combined with a probable reduction in irritation through minimizing the use of irritating surfactants.
A second deterrent for using the phenol-based actives results from incompatibility between these compounds and commonly used surfactants, specifically anionic, non-ionic and amphoteric surfactants. Because of this adverse effect, the surfactant choices are limited to those classes remaining, namely quaternary ammonium compounds and amine oxides. These two surfactant types, however, have their detrimental properties. Quaternary ammonium compounds do not produce an aesthetically pleasing hand wash due to their inability to foam, and these compounds are comparatively much more expensive than the commonly used surfactant classes. Amine oxides, much like quaternary ammonium compounds, lack the full gamut of necessary aesthetic properties to produce a commercially viable hand wash. Although amine oxides have relatively standard flash foaming properties, the foam is not stable, and again this surfactant class is expensive compared to the commonly used surfactants. Therefore, there is a need in the art for a surfactant combination that allows for an aesthetically pleasing hand wash that also has the necessary antimicrobial properties.
Current consumer trends drive for a hand wash which copiously foams, has the desired antimicrobial properties, and does not irritate skin. To produce a hand wash that foams to the extent desired, anionic surfactants are usually added. But these surfactants usually deactivate the active ingredient and are detrimental to the skin. The next best choice for foaming enhancement are the amphoteric surfactants. Although they do not foam as greatly as the anionic surfactants, they do have better skin compatibility. Again, amphoteric surfactants are not usually compatible with the active agents. Non-ionics, although excellent in militating against irritation, do not foam to an appreciable extent, and, because of this, their use is limited. Moreover, non-ionic surfactants usually deactivate the active ingredients. Therefore, there is a need in the art for a surfactant combination which meets the desired foaming properties, is of low irritancy, and provides highly efficacious properties.
One step used to reduce irritancy in a hand wash is reducing the amount of active ingredient within the hand wash. This reduction, although reducing the irritancy of the hand wash, causes a detrimental effect on the washing properties. This reduction requires the use of other ingredients within the hand wash that have nearly no negative affect on the efficacious properties of the active agent. This minimization of negative interactions requires two possible arrangements. One, the use of other ingredients which only positively affect or at least have no negative affect on the active ingredient, or two, any ingredients which negatively impact the active ingredient are minimized.
This invention provides an antimicrobial hand wash comprising a phenol-based active ingredient and an amphoteric surfactant selected from the group consisting of derivative compounds of a fatty amine with a nitrogen atom bound to at least one, but not greater than two, propionic acids. Specific, non-limiting examples of such acids include disodium capryloamphodiactate, cocaminpropionic acid and cocoamphodipropionic acid. Specific non-limiting examples of useful active ingredients include triclosan, 2,2′-dihydroxy-5,5′-dibromodiphenyl ether, pcmx, ortho-phenylphenol, and mixtures thereof.
In another embodiment, this invention provides an antimicrobial hand wash comprising a phenol-based active ingredient and a quaternary ammonium compound selected from the group consisting of polyethylene glycol (PEG) derivatives of a quaternary ammonium salt of a fatty amine, polypropylene glycol (PPG) derivatives of a quaternary ammonium salt of a fatty amine, and mixture thereof. The PEG and PPG derivative compounds are cationic surfactants that have the uncanny ability to solubilize the active ingredient. Even upon dilution of the formulation into water, the active ingredients remain in solution. Thus, by employing the cationic PEG and/or PPG derivative surfactant, the total solids amount in the formula is minimized, which ultimately relates to reduced skin irritation. The reduction in solids content is a result of not having to employ a significant amount of additional solubilizing surfactants and/or glycols.
In yet another embodiment, this invention provides an antimicrobial hand wash comprising a phenol-based active ingredient; an amphoteric surfactant selected from the group consisting of derivative compounds of a fatty amine with a nitrogen atom bound to at least one, but not greater than two, propionic acids; and a quaternary ammonium compound selected from the group consisting of polyethylene glycol (PEG) derivatives of a quaternary ammonium salt of a fatty amine, polypropylene glycol (PPG) derivatives of a quaternary ammonium salt of a fatty amine, and mixture thereof.
In particular embodiments of the foregoing hand washes, additional compounds are employed, as generally known, to hone the aesthetic properties of the hand wash. These compounds include dyes, fragrances, foam modifying agents skin conditioning agents, including but not limited to humectants, emollients, and anti-static agents.
In accordance with this invention, a method for producing an antimicrobial hand wash includes the steps of creating an active ingredient premix comprised of a phenol-based active ingredient and a polyethylene glycol derivative of a quaternary ammonium salt of a fatty amine, wherein the polyethylene glycol derivative dissolves at least a portion of the phenol-based active ingredient. In another step, a water-based premix is created comprised of water and a supplemental surfactant package. The active ingredient premix is mixed with the water-based premix. In this production process, it is not necessary to heat the premix solution to dissolve the active ingredient. As a result, creating the hand wash requires less mixing time and less energy input.
Antimicrobial hand washes in accordance with this invention are aqueous hand washes including at least one active ingredient incorporated into water in combination with at least one surfactant. Although this describes the basic make up, as is generally common in the art, to produce an acceptable end hand wash product, multiple surfactants are employed, as are skin conditioning agents, pH adjusting agents, foam modifying agents, preservatives, dyes, fragrances, and the like.
The antimicrobial hand wash contains at least one active ingredient, which is generally appreciated as a term of art for those compounds that produce acceptable time-kill antimicrobial activity to be suitable for sanitizing. More specifically, the hand wash herein has efficacious properties against both Gram-positive and Gram-negative microorganisms. For purposes of this disclosure, the terms “active ingredient” and “actives” are to cover compositions that have greater than 2 log kill reduction on both Gram-negative bacteria, specifically Klebsiella pheumoniae, and Gram-positive bacteria, specifically Staphylococcus aureus. In this invention, phenol-based active ingredients are employed.
The phenol-based active ingredients useful in this invention are exemplified by the following compounds, and may be used alone or in combination:
wherein Y is chlorine or bromine, Z is SO2H, NO2, or C1-C4 alkyl, r is 0 to 3, o is 0 to 3, p is 0 or 1, m is 0 or 1, and n is 0 or 1. In preferred embodiments, Y is chlorine or bromine, m is 0, n is 0 or 1, o is 1 or 2, r is 1 or 2, and p is 0. In especially preferred embodiments, Y is chlorine, m is 0, n is 0, o is 1, r is 2, and p is 0. A particularly useful 2-hydroxydiphenyl compound has the structure:
having the adopted name, triclosan, and available commercially under the tradename IRGASAN DP100, from Ciba Specialty Chemicals Corp., Greensboro, N.C. Another useful 2-hydroxydiphenyl compound is 2,2′-dihydroxy-5,5′-dibromodiphenyl ether. Additional bisphenolic compounds are disclosed in U.S. Pat. No. 6,113,933, incorporated herein by reference.
wherein R1 is hydro, hydroxy, C1-C4 alkyl, chloro, nitro, phenyl, or benzyl; R2 is hydro, hydroxy, C1-C6 alkyl, or halo; R3 is hydro, C1-C6 alkyl, hydroxy, chloro, nitro, or a sulfur in the form of an alkali metal salt or ammonium salt; R.sub.4 is hydro or methyl; and R5 is hydro or nitro. Halo is bromo or, preferably, chloro.
Specific examples of phenol derivatives include, but are not limited to, chlorophenols (o-, m-, p-), 2,4-dichlorophenol, p-nitrophenol, picric acid, xylenol, p-chloro-m-xylenol, cresols (o-, m-, p-), p-chloro-m-cresol, pyrocatechol, resorcinol, 4-n-hexylresorcinol, pyrogallol, phloroglucin, carvacrol, thymol, p-chlorothymol, o-phenylphenol, o-benzylphenol, p-chloro-o-benzylphenol, phenol, 4-ethylphenol, and 4-phenolsulfonic acid. Other phenol derivatives are listed in WO 98/55096 and U.S. Pat. No. 6,113,933, incorporated herein by reference.
wherein X is sulfur or a methylene group, R1, and R′1, are hydroxy, and R2, R′2, R3, R′3, R4, R′4, R5, and R′5, independent of one another, are hydro or halo. Specific, nonlimiting examples of diphenyl compounds are hexachlorophene, tetrachlorophene, dichlorophene, 2,3-dihydroxy-5,5′-dichlorodiphenyl sulfide, 2,2′-dihydroxy-3,3′, 5,5′-tetrachlorodiphenyl sulfide, 2,2′-dihydroxy-3,5′,5,5′,6,6′-hexachlorodiphenyl sulfide, and 3,3′-dibromo-5,5′-dichloro-2,2′-dihydroxydiphenylamine. Other diphenyl compounds are listed in WO 98/55096, incorporated herein by reference.
In particular embodiments, the phenol-based active ingredient is selected from triclosan, 2,2′-dihydroxy-5,5′-dibromodiphenyl ether, pcmx, ortho-phenylphenol, and mixtures thereof.
The hand wash formulations of this invention are typically comprised of from about 0.01 to 10 weight percent (wt %) of the phenol-based active ingredient. In particular embodiments, the active ingredient makes up from about 0.05 to 1 wt % of the formulation, and in other embodiments, from about 0.2 to 0.4 wt %.
In its most basic form, the hand wash formulation further includes at least one amphoteric, more particularly zwitterionic, surfactant selected from the group consisting of derivative compounds of a fatty amine with a nitrogen atom bound to at least one, but not greater than two, propionic acids. Preferably the fatty chain has from 6 to 20 carbon atoms. Specific non-limiting examples of such zwitterionic surfactants include disodium capryloamphodiactate, cocaminopropionic acid, lauraminopropionic acid, cocoamphodipropionic acid, lauriminodipropionic acid, and lauramphodipropionic acid, and mixtures thereof. These specific zwitterionic surfactants have unexpectedly been found to be compatible with phenol-based active ingredients such that they maintain the antimicrobial efficacy of the active while still allowing for an increase in foam quality when it is desired to provide a hand wash formulation that foams. Given the substantial commercial success of foamed hand washes, it is envisioned that a foaming hand wash formulation in accordance with this invention is most preferred. The most preferred zwitterionic surfactant is cocaminopropionic acid because of its excellent compatibility with the phenol-based active ingredients.
The hand wash formulations of this invention are typically comprised of from about 0.05 to 25 weight percent (wt %) of such zwitterionic surfactants. In particular embodiments, the zwitterionic surfactant makes up from about 0.1 to 12 wt % of the formulation, and in other embodiments, from about 0.5 to 2.5 wt %.
In other embodiments, the antimicrobial hand wash further includes a quaternary ammonium compound. More specifically, the quaternary ammonium compound is chosen due to its unique ability to at least partially dissolve the active ingredient even at low usage levels, as low as a three to one molar ratio of the quaternary compound to the phenol-based active ingredients. The quaternary ammonium compound is preferably selected from polyethylene glycol (PEG) derivatives of a quaternary ammonium salt of a fatty amine, polypropylene glycol (PPG) derivatives of a quaternary ammonium salt of a fatty amine, and mixtures thereof. Preferably the fatty chain contains from about 6 to 20 carbon atoms. The most preferred compound is PEG-5 oleammonium methosulfate. PEG-2 oleammonium chloride and PEG-15 oleammonium chloride are also particularly preferred.
Whereas, in the prior art it has been necessary to heat the solution to solubilize the active ingredient, the disclosed quaternary ammonium compounds at least partially solubilize the active ingredient at room temperature, thus allowing the hand wash formulation to be mixed without the addition of heat. These quaternary cationic surfactants, when employed, allow for a lesser amount of total surfactants than were normally required in the prior art to dissolve active ingredients. Because surfactants can be irritating to the skin, their reduction in the hand wash formulation is advantageous, providing formulations with increased efficacious properties, due to the solubilized active ingredient, and with minimal irritating ingredients, due to the use of a lesser amount of surfactants. Whereas the prior art uses a normal about of solids within a formulation being from about 12 to 30 weight percent, the preferred embodiments herein include only from about 3 to 5 weight percent solids.
The hand wash formulations of this invention are typically comprised of from about 0.01 to 10 weight percent (wt %) of the quaternary ammonium compound. In particular embodiments, the quaternary ammonium compound makes up about 0.05 to 5 wt % of the formulation, and in other embodiments, from about 0.15 to 2 wt %. The quaternary ammonium compound dissolves at least a portion of the phenol-based active ingredient, and, preferably, dissolves substantially all of the active ingredient.
In its most preferred form, an antimicrobial hand wash in accordance with this invention will include each of the ingredients disclosed above, namely, phenol-based active ingredient, zwitterionic surfactant, and quaternary ammonium compound, as disclosed. These ingredients are balance with water. However, as known, additional compounds are typically used to produce an acceptable hand wash for consumer use. These compounds include, but are not limited to, foam modifying agents, pH adjusting agents, emollients, humectants, skin conditioning agents, dyes and fragrances. Herein, they may be employed in amounts and for reasons known in the prior art. Thus, additional surfactants may be employed but are not necessary.
Benefits are also realized by creating hand washes without all three main ingredients as just disclosed. Thus, this invention contemplates hand wash formulations including phenol-based active ingredient and zwitterionic surfactant (i.e., without the beneficial quaternary ammoniums disclosed) and other hand wash formulations including phenol-based active ingredient and quaternary ammoniums as disclosed (i.e., without the beneficial zwitterionic surfactant).
Although the zwitterionic surfactants do not foam inexhaustibly, they do promote foaming. Also, they have little irritation so there is no critical upper limit for the amount at which they are used in the hand wash. Although, the quaternary ammonium compound does not foam to any appreciable extent, it has unique interactions with the active ingredients (i.e., it dissolves at least a portion thereof), allowing for maximum efficacious properties.
To make hand wash formulations in accordance with prior art processes, generally all ingredients are mixed and brought to a temperature of about 60° C. to 70° C., with the mixing continuing for hours to create a homogeneous mix. In accordance with this invention, a hand wash formulation can be made through a “cold” process that does not require heating formulation mixtures.
A method for producing an antimicrobial hand wash in accordance with this invention includes creating an active ingredient premix including an active ingredient and a quaternary ammonium compound selected from polyethylene glycol (PEG) derivatives of a quaternary ammonium salt of a fatty amine, polypropylene glycol (PPG) derivatives of a quaternary ammonium salt of a fatty amine, and mixtures thereof, wherein the quaternary ammonium compound dissolves at least a portion of the active ingredient. A second premix is made containing water, the zwitterionic surfactant of choice, and any extra compounds as seen fit to create an aesthetically pleasing hand wash. These two premixes are combined and mixed until homogeneous.
The combination of the active premix and the water premix may proceed in one of two fashions, either the active premix may be added to the water premix or the water premix may be added to the active premix. Also, the combining of these two solutions may occur at any time during the addition of compounds to the water. More precisely, the two premixes may be added prior to any compound addition to the water premix, or after the addition of any number or compounds. This addition of the active premix should proceed only after the polyethylene glycol derivative dissolves at least a portion, and preferably substantially all, of the active ingredient. Through this production process, it is not necessary to heat the solution, i.e. the production of the hand wash may proceed at ambient temperature, to dissolve the active ingredient, thereby creating a hand wash which requires less mixing time. This yields cost savings via shorter turn-over time and energy savings.
The use of amphoteric surfactants in antimicrobial hand washes containing triclosan, and/or p-chloro-m-xylenol, is a rarity because these amphoteric surfactants normally deactivate the active ingredients. Unexpectedly, it has been found that there are a few amphoteric surfactants, more specifically zwitterionic surfactants, that do not inhibit the antimicrobial properties of the active ingredient. The following sample creation and testing will demonstrate this discovery.
Multiple hand wash test samples were made in accordance with the formulation provided directly below, wherein the zwitterionic surfactant was changed for each sample. The zwitterionic surfactants employed, as well as the efficacy of the resultant hand wash in reducing Escherichia coli, are reflected in Table 1. The process for making the samples was as follows: the active ingredient was added to the surfactant and mixed until all of the solid active ingredient dissolved into the surfactant. If required, heat was administered to dissolve the active ingredient. Water was then added to this “active premix”. The samples were tested against Escherichia coli by inoculating a sample of the organism with a loopful of the hand wash solution for 15 seconds. A sample was then taken from the broth and incubated on a nutrient rich agar plate for 48 hours prior to counting. The formulation was as follows:
Of the numerous zwitterionic surfactants tested only a few actually did not inhibit the active ingredient. With the diminished log reductions, the surfactants become less and less desirable for use in an antimicrobial hand wash. The class of surfactants is limited to disodium capryloamphodiacetate and those of compounds containing a nitrogen atom bound to at least one but not greater than two propionic acid groups, and a fatty acid chain from carbon length 6 to 20.
The efficacy of a particular hand wash in accordance with this invention was tested against multiple microorganisms and strains thereof. The organisms tested varied greatly, including bacterial, yeast and fungal species, and are of the type most commonly found in settings where clean, sanitized hands are most desired. The test procedure was as follows: the hand wash was diluted to 99% volume/volume of the original concentration, and this new sample was then added to a second solution containing the microorganism to be tested. This inoculation occurred at 15 and 30 seconds. The samples were then plated onto agar plates and incubated. The log reduction was calculated by comparing the values between a non-inoculated sample and the sample inoculated with the hand wash.
The hand wash contained the following ingredients:
Acinetobacter baumannii
Aspergillus flavus
Aspergillus niger
Bacillus megaterium
Bacteroides fragilis
Burkholderia cepacia
Campylobacter jejuni
Candida albicans
Candida tropicalis
Citrobacter freundii
Clostridium difficile
Clostridium perfringens
Corynebacterium
diphtheriae
Enterococcus faecalis
Enterococcus faecalis
Enterococcus faecium
Epidermophyton floccosum
Escherichia coli
Escherichia coli
Escherichia coli
Haemophilus influenzae
Klebisella pheumoniae
Klebsiella pneomoniae
Lactobacillus plantarum
Listeria monocytogenes
Penicillum citrinum
Proteus mirabilis
Proteus vulgaris
Pseudomonas aeruginosa
Pseudomonas aeruginosa
Salmonella choleraesuis
Salmonella choleraesius
Salmonella choleraesuis
Serratia marcesens
Shigella dysenteriae
Shigella sonnei
Staphylococcus aureus
Staphylococcus aureus
Staphyloccus aureus
Staphylococcus epidermidis
Staphylococcus
haemolyticus
Staphyloccus hominis
Staphylococcus
saprophyticus
Streptococcus pneumoniae
Streptococcus pyogenes
Trichophyton
mentagrophytes
The hand wash exhibited broad, fast acting antimicrobial activity against Gram-positive and Gram-negative bacteria. There was a limited degree of efficacy against molds, but the log kill was sufficient to not impede the use of this hand wash as a sanitizer. Of the 46 organisms tested the hand wash had greater than 5.0 log reduction on 26 of the organisms; 7 organisms had greater than 4.0 log reduction; 5 organisms had greater than 3.0 log reduction; 3 organisms had greater than 2.0 log reduction; 1 organism had greater than 1.0 log reduction; and the remaining four had below one log reduction. The four organisms that had less than one log reduction were Aspergillus niger, Trichophyton mentagrophytes, Penicillum citrinum and Aspergillus flavus, all of which are fungus colonies.
As disclosed, hand washes made in accordance with the particularly preferred embodiments of this invention have a reduced level of solids. To show this, the solids content of the hand wash formulation of Example Two, above, was compared with competitive antimicrobial hand washes. Competitive antimicrobial hand washes were tested for solids content by placing a weighed sample into a 50° C. oven for 48 hours to ensure all the volatile components were removed. After the 48 hours the samples were removed from the oven and allowed to cool to room temperature. Then the samples were weighed a second time and the percent solids calculated from the two values.
The total solids amount of the hand wash of Example Two was 8.4 weight percent. Compare this value to the average value from the competitive hand washes, 18.95 weight percent. There is over a fifty percent reduction in the total solids content of the hand wash.
Because of the reduced amount of solids in the present hand washes, the irritancy of the hand wash is minimized. As seen in Example Three, the solids of a hand wash described herein has solids content that is nearly 50% of the average for competitive antimicrobial hand washes. This reduction in solids shows a positive effect on reducing the irritancy of the hand wash. In this the hand wash of Example Two was diluted in deionized water to one percent of the original volume. The sample was then applied to a patch. This patch, after being soaked in the solution, was placed on a test subject's skin for a set amount of time. After the patch sat on the skin for the required time, moisture measurements and redness values were assigned. Also similarly tested were both positive, sodium lauryl sulfate, and negative, Johnson and Johnson Baby Oil, controls. These two samples were diluted to 0.2 percent of the original volume into deionized water.
The scale or classification is as follows:
Per Table Four, the hand wash of this invention has a very low irritancy score, lower in fact than the negative control. This low irritation comes from the reduction of solids in the hand wash, because some of the compounds found in the hand wash are appreciated as irritants, primarily the surfactants. Their reduction ensures a non-irritating hand wash, which fits with one of the criteria for use as a repeated hand wash.
One of the desires of end users for hand washes is copious amounts of foam during the hand wash experience. One way to test the amount and type of foam created using a hand wash is to dilute the hand wash sample into water and then shake the sample to produce foam. The process used here was a 100 fold dilution of 1 mL of the hand wash of Example Two into deionized water. This solution was mixed gently to prevent foaming and then added to a 500 mL graduated cylinder. The cylinder was stoppered and the sample was inverted ten times. The sample was then set on a flat surface, the top was removed, and the sample sat for 5 minutes. Once the inversions were done, the height of the foam was recorded and the volume of liquid was subtracted from this to yield the height of the foam. After 5 minutes the foam height was measured again and the volume of liquid was subtracted from this.
The first measurement of the foam height gives an indication of the flash foaming ability of the hand wash. This means the hand wash's ability to produce quick amounts of foam requiring little mechanical force to generate it. The second measurement is a relative measure of the stability of the foam. While washing, the foam deteriorates, but the longer the foam lasts in this test, the more likely it will last during a hand wash.
The product on the bottom of the prototype disclosed herein. Although the hand wash of Example Two has much less solids than competitive counterparts, the foam generated was near the average of all the other samples and well within one standard deviation of this norm.
In light of the forgoing, it should be evident that the present invention provides improvements in hand wash formulations and their method of manufacture. While particularly preferred embodiments of this invention have been here disclosed in accordance with the dictates of the patent statutes, the present invention, also in accordance with patent statutes and rules of interpretation, is not to be limited thereto or thereby. The following claims will establish the scope of this invention.
This continuation application claims priority from U.S. patent application Ser. No. 11/435,070 filed on May 16, 2006, which is incorporated herein by reference in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| Parent | 11435070 | May 2006 | US |
| Child | 12818672 | US |
