BASED SURFACTANTS

CROSS REFERENCE TO RELATED U.S. APPLICATIONS This patent application relates to, and claims the priority benefit from,

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March 7, 2005, in English, entitled HIGH ALCOHOL CONTENT FOAMING COMPOSITIONS WITH SILICONE-BASED SURFACTANTS, and which is incorporated herein by reference in its entirety.

FIELD OF THE INVENTION

The present invention relates to compositions with high contents of lower alcohol (C _1-4 ) that could be dispensed as a foam both under low pressure from unpressurized containers and from pressurized containers achieved with an aerosol packaging system. The compositions to be dispensed as foams contain a silicone-based surfactant and when mixed with air provide a stable alcohol foam which can be used for personal cleaning or for disinfecting purposes.

BACKGROUND OF THE INVENTION

Ethanol and/or lsopropyl alcohol and/or n-propyl alcohol compositions with at least 60% percent v/v (approximately 52% by weight) are well known to be antibacterial, therefore widely accepted for disinfecting purposes. Nonetheless due to the inherent characteristics of alcohol, it is perceived that the higher the content the better the product and a solution with higher than

60% by volume alcohol content is more desirable.

Alcohol disinfectant solutions are generally thickened in order to eliminate the waste and facilitate spreading the composition throughout the desired area. It is also known that other than gelling agents one can use paraffin or waxes to achieve thickening of a solution with high alcohol concβπtrstion. Such s composition with lanolin sddθd to ΓΘUUCΘ thθ πiθltiny point closer to body temperature is described in United States Patent No. 2,054,989. One of the disadvantages of gels and the above-mentioned type of thick alcohol-containing compositions is that if they do not leave a tacky feeling on the hands after one use (although some do), the effect builds up after repetitive use during the day, making it necessary to eventually wash off the thickeners before continuing the usage of an alcohol antiseptic solution. The present invention if formulated for the above-mentioned type of product does not leave such a feel, and does not need to be washed off after repeated use. Generally speaking a high alcohol content disinfectant solution disinfects but does not clean. In order to make them disinfect and clean, so much soap would need to be added to the solution that the skin would feel soapy and disagreeable resulting in a formulation that would have little commercial appeal. Nonetheless, a non-irritant skin disinfecting formulation with a high content of a lower alcohol for use as a skin-washing agent has been successfully achieved by combining emulsifiers, surfactants and skin emollients as described in United. States Patent No. 5,629,006.

Surfactants other than for cleaning purposes are also used for spreading an aqueous composition containing one or more active substances rapidly and evenly over a surface due to their wetting properties. The use of

good wetting agents definitely improves the efficient use of active substances in different compositions as described in United States Patent No. 5,928,993.

Although a high alcohol content disinfectant solution has good disinfectant characteristics, it has a sharp smell and is generally perceived to csϋSΘ drying of lhs skin, chsrsc-tθπstics which csπ slso be diminished to « desirable level in the present invention.

A foam product with greater than 40% v/v alcohol, which is easy and safe to use, is desirable over conventional liquid, gel or ointment type composition products. The concentration of alcohol already poses a hazard in itself, and there are many applications in which the perceived risk may be diminished if it could be dispensed as a foam. A foam intended to be useful as a skin disinfecting agent must have a uniform consistency, spreadability, cleansing ability, and have a pleasant feel, i.e. have rapid breaking power when pressure is applied; all of which present a challenge.for a high lower alcohol content composition.

The description of an aqueous foaming skin disinfecting composition using 15% w/w alcohol as a co-solvent, which requires no pressurized container or added propellant to produce the foam, is described in United States Patent No. 3,962,150. The foam-forming agents utilized heretofore, have been incapable of forming stable foams when the liquid phase has high alcohol content without using other ingredients. Furthermore, lower alcohols have been considered to be defoamers rather than foam-promoting chemicals. According to Klausner, in United States Patent No. 3,131 ,153, if more than 64% alcohol is used non-

homogeneous compositions are obtained. The compositions in the patent required propellant to foam and the foams produced were of limited stability.

Various examples of compositions with a high content of a lower alcohol that are dispensed as a foam have been described, although for the purpose uf lhe present Invention lhe concentrations of alcohol and the levels of other ingredients are not suitable. More importantly, the use of propellants and aerosol containers to generate the foam is not desirable. For example, the compositions described in United States Patent No. 5,906,808 disclose a product that uses an emulsifying wax NF, and a combination of stearyl and cetyl alcohol, or other wax combinations, which improve the foaming performance of the composition, in combination with cetyl lactate, to produce a 0.8% chlorhexidine gluconate alcohol product.

United States Patent No. 5,167,950 issued to Lins discloses a foam product which requires a propellant and where no surfactant is added as a cleaning agent. The composition disclosed in this patent is based upon using an emulsifier system (fatty alcohol ROH 16-22 carbons) in combination with the use of a thickening agent (carbomer, klucel, etc.) to produce an antimicrobial aerosol mousse having a high alcohol content. The mousse includes alcohol, water, a polymeric gelling agent and a surfactant system comprising a C16-C22 alcohol, aerosol propellant and a non-ionic polyethoxylated surfactant.

Despite the work done to date it has been shown that there is little specific knowledge on how foams react and are formed, and surprisingly formulations that might seem not foamable result in the best foam producing ones while other formulations which seemed to have been producing foam

even while being prepared did not perform well at all in some non-aerosol foam dispensers. The behaviour of aqueous foams is not the same as that of an alcohol foam.

Silicone-based surfactants have been used in applications requiring lowering of u ^~ \& surface tension and increased wetting properties, especially in applications that require materials to be compatible with solvent systems other than water and non-reactive to other components in the compositions. Silicone surfactants are desirable since they can achieve relatively low surface tension levels with relatively low concentrations in the compositions of interest Commercial examples of the exploitation of the advantage of the low surface tension levels achieved using Silicone based surfactants are crop protection products, printing inks, paints, floor coatings, etc. The characteristics mentioned above make silicone surfactants a candidate for the intention of this patent. It would be very advantageous to have alcohol based disinfecting formulations containing silicone-based surfactants which may be dispensed as a foam under low pressure conditions and/and or through an aerosol packaging system. Further, it would be very advantageous and desirable to find a foaming agent that could be used in concentrations that would allow it to be used in products that can remain in the area on which they have been applied and do not need to be rinsed or wiped off due to small amounts of residue remaining after evaporation. Thus it would also be very advantageous to provide foams that do not leave an unpleasant sticky after-feel as most commercial alcohol gel products are known to, or which clog up the dispensing equipment used to dispense the foams. Silicone-based surfactants

are more than desirable for the purpose aforementioned since they are currently used as desirable cosmetic ingredients in creams, lotions, and other cosmetics due to their soft after-feel and properties. i

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The present invention provides high alcohol content compositions, which contain a surfactant/cleaning agent as well as a disinfectant/cleaning/solvent/carrier that causes very little drying to the skin or the hands of the user and is able to be dispensed as a foam from both pressurized and non-pressurized systems dispensing systems.

The present invention provides high alcohol content compositions that are able to be dispensed as a foam which are readily spread over the desired surface for the particular application. The present compositions can be formulated as an antimicrobial alcohol foam. The foamable compositions when dispensed from a suitable dispenser are stable and do not require the use of propellants and pressurized containers although if used would also foam.

Accordingly, the present invention provides foamable alcohol composition, comprising; a) a C-ι-4 alcohol, or mixtures thereof, present in an amount greater than about 40% v/v of the total composition; b) an effective physiologically acceptable silicone-based surface active agent, which includes a lipophilic chain containing a silicone backbone ( - (R ₂ Si-O) _n - ), for wetting and foaming present in an amount of at least 0.01 % weight percent of the total composition; and

c) water present in an amount to balance the total composition to 100% weight percent.

In this aspect of the invention the effective silicone-based surface active agent is present in an amount from about 0.001 % to about 10.0% weight percent cf ins total composition which is physiologically acceptable so it can be used in personal care type products.

In a preferred embodiment of the invention the silicone-based surfactant may be a Bis-PEG-[10-20] dimethicone, a 3-(3-Hydroxypropyl)- heptamethyltrisiloxane, an ethoxylated silicone-based surfactant, a Bis- PEG/PPG 18/6 Dimethicone, a Polyether-modified polysiloxane or a

Polysiloxane betaine, or mixtures thereof. The present invention also provides an alcohol disinfecting composition, comprising; a) a) an alcohol Ci _-4 , or mixtures thereof, present in an amount between about 60% to about 80% v/v of the total composition; b) an effective physiologically acceptable silicone-based surface active agent for wetting and foaming present in an amount from about 0.01% to about 10.0% weight percent of the total composition; c) a foam stabilizing agent present in an amount from about 0.01 to about 12.0 % weight percent; d) any one of moisturizers, emollients and combinations thereof present in an amount from about 0.05 to about 5.0 % weight percent; and e) water in an amount to balance the total composition to 100% weight percent.

The present invention also provides a composition concentrate, comprising;

a) an effective silicone-based surface active agent for wetting and foaming present in an amount of at least 0.01% weight percent of the total composition 0.01 to about 15.0 %; b) a foam stabilizing agent including at least from about 0.01 to about

c) one of moisturizers, emollients and combinations thereof present in a range from about 0.05% to about 5.0%; and d) water.

DETAILED DESCRIPTION OF THE INVENTION

Definitions

The term "emollient" as used herein refers broadly to materials which are capable of maintaining or improving the moisture level, compliance, or appearance of the skin when used repeatedly. The term "emulsifier" as used herein refers to surfactants or other materials added in small quantities to a mixture of two miscible liquids for the purpose of aiding in the formation and stabilization of an emulsion.

The phrase "emulsifying ingredients" as used herein is synonymous with emulsifier defined above. The term "emulsion" as used herein refers to a colloidal dispersion of one liquid in another.

The term "surfactant" as used herein is the widely employed contraction for "surface active agents" which is the descriptive generic term for materials that preferentially adsorb at interfaces as a result of the presence of both, lipophylic and lipophobic structural units, the adsorption generally

resulting in the alteration of the surface or interfacial properties of the system.

The term "silicone-based surfactant" as used herein refers to a surface active agent in which the lipophylic chain contains a silicone chain, also described as any organosilicon oxide polymer in which the structural unit is usually cosϊipπsifiQ; — R. ₂ Si-O)n— whβrs R is s monovalent OΓQSΓHC radical, sπd which enables the composition in which it is contained to clean, wet and foam.

The phrase "foam stabilizer" as used herein refers to an additive that increases the amount or persistence of foam produced by a surfactant system. The term "disinfect" as used herein means to destroy or reduce harmful microorganisms.

The phrase "physiologically acceptable" as used herein means a material that does not usually produce irritation or toxicity when applied to the skin and is acceptable by users to apply to human skin "Foam" as used herein means a liquid and a gas mixed to form a mass of small bubbles that has a structure that lasts for a variable length of time.

A bubble is a cell of gas surrounded by a film of liquid.

The term "aerosol" as used herein means a package and delivery system, and the. product delivered, in which a pressurized gas is used to force the product out for dispensing. The gas may or may not be dispensed with the product.

An "aerosol foam" is a foam dispensed out of an aerosol package and delivery system as defined above.

The phrase "low pressure" in the context of producing a foam as used herein means a pressure of around an atmosphere or less such as when

dispensing the foam from an unpressurized conainer. Typically when foams are dispensed from aerosol containers the foam is considered to be being dispensed under high "pressure" conditions.

The present invention provides foamable alcohol compositions which Include slllconc-bassd surfactants with high contents of lower alcohol (G ₁ - ₄ } able to be dispensed as a foam under low pressure conditions from unpressurized containers and through an aerosol packaging system. The present foamable compositions when mixed with air deliver a stable foam to provide an alcoholic liquid solution which can be used for personal cleaning or for disinfecting purposes and which breaks on pressure application such as when a user rubs their hands or when applied over a surface. All percentages provided herein are based on the total weight unless otherwise indicated.

The alcohol used in the present invention is a lower hydrocarbon chain alcohol such as a C ₁ - ₄ alcohol. The preferred alcohol is chosen from ethanol, 2-propanol, or n-propanol, most preferably ethanol, well accepted by Health -

Care personnel as an adequate disinfectant at the right percentages. It will be appreciated by those skilled in the art that if the alcohol used in the formulation is ethanol or a combination of ethanol with one or more of the other C- ₁ - ₄ alcohols the ethanol preferably will be properly denatured to meet the local regulations of the targeted markets, but for the purposes of this patent it will be referred just as ethanol without it being specific as to whether it has been denatured. The compositions may use a single alcohol or as mentioned a blend of two or more alcohols may comprise the alcohol content of the composition

A significant and very surprising achievement of the present invention is that compositions suitable for disinfecting have been made containing greater than 40% v/v alcohol and a silicone-based surfactant able to be dispensed as a cosmetically appealing foam from both, low pressure iΛJi iUlUUi iό αH<-! iϋϋJUyi i an <3<7i uo«->l μαUru-iyiϊ iy &»oici i i.

The use of a silicone-based surfactant is the key ingredient as the primary foaming agent in the compositions designed to foam. Silicone surfactants have various interesting properties such as leaving little residue, being able to function in harsh chemical and thermal environments; they have an unparalleled wetting power, characteristics that are in general better than those of traditional surfactants, they show better surface-active properties in organic solvents, and that have made them widely used for applications in coatings, oilfield, material finishes, cleaning, paints, pesticides application, etc. Traditional surfactants have carbon chains as the hydrophobic portion of the molecule. The hydrophile that is added to the carbon chain will determine the solubility and the general class of surface active agents as anionic, cationic, non-ionic or amphoteric. The silicone-based surfactants suitable for the compositions disclosed herein may include, but are not limited to, phosphate esters, sulphates, carboxylates, Imidazole quats, Amino Quats,

Alkyl Quats, Amino propionates, ethoxylates, glycerol esters, amine oxides, acetylenic alcohol derivatives, phosphates, carbohydrate derivatives, sulfonates, betaines, Isethionates, esters, polyamides, and hydrocarbon surfactants that have a silicone chain -(F^-Si-O) _n - and are compatible with the other components being used for a particular formulation.

From the different silicone surfactants commercially available, samples from different manufacturers and different chemical surfactant groups were evaluated. Particularly, the Silicone Polyethers, also known as dimethicone copolyols showed the best performance. Amongst them, samples of multi- pendant and linsar-difunctlonal showed activity but thε later was found to give superior foam properties. This is interesting as well as unexpected since in most water based applications if one of the multi-pendant or linear-difunctional silicone surfactatns produces foam in water based mixtures, the other does not perform as well. However this is in agreement with the observations that foaming alcohol compositions behave quite differently from foaming water- based compositions.

While trying different surfactants, mixtures of two or more were evaluated to find out whether there was any synergy identifiable to optimize usage and foam performance. While some synergies were identified, it was also found that particularly difunctional silicone surfactants Bis-PEG [10-20]

Dimethicones were the best when used alone. The notation Bis-PEG-[10-20] means all the Bis-PEG compounds having from 10 to 20 repeating oxyethylene groups. This applies to all other constituents as well. Specifically Bis-PEG 12 dimethicone and/or Bis-PEG-20 dimethicone and/or Bis-PEG-17 dimethicone are preferred along with 3-(3-Hydroxypropyl)- heptamethyltrisiloxane, ethoxylated, acetate, a polyether-modified polysiloxane and a polysiloxane betaine, showed promising results but not as good as the dimethicone ones.

In preferred embodiments of the compositions, the effective silicone- based surface active agent may be a physiologically acceptable Bis-PEG-[10-

20] dimethicone , a 3-(3-Hydroxypropyl)-heptamethyltrisiloxane, ethoxylated, acetate, a Polyether-modified polysiloxane or a Polysiloxane betaine, or mixtures thereof from about 0.01 % to about 10.0% weight percent of the total composition. It was surprisingly found that despite the characteristics of silicone- based surfactants, there is little or no information on their use to produce a foamable product with high alcohol content under either, low pressure conditions or through an aerosol packaging system.

Furthermore, in order to obtain a high alcohol content product able to produce a foam even if no pressurized containers or propellants are used, surface tension values as low as possible are required so that the pressure required to produce such foam by hand pumps and mechanical means would be sufficient.

During the development of the present invention, it was unexpectedly found that a relatively stable quick breaking foam could be obtained when using just ethanol and the silicone-based surfactant with as high as 80%v/w while using traditional surfactants at higher percentage yielded results that could not be even slightly similar and no foam at all could be obtained.

In order to achieve a commercially suitable formulation (one that lasts long enough for the purpose of use in disinfecting applications)., reducing the amount of silicone-based surfactant used while using the assistance of other ingredients such as secondary surfactants, emulsifiers, foam stabilizers, fragrances, and the like ingredients employed in cosmetics, aerosols, toiletries, personal care, etc. is one of the approaches that were followed. One of the commercial products obtained uses emulsifiers and polyethoxylated

fatty acid surfactants disclosed in United States Patent Nos. 5,167,950 and 6,090,395, both incorporated herein by reference, while other examples use a combination of different foam stabilizers to achieve a similar result.

Examples of secondary surfactants that may be used in the present compositions include other silicone surfactants, fluorinatsci surfactants, alkylglucosides, a poly(ethoxylated and/or propoxylated)alcohol, a poly(ethoxylated and/or propoxylated)ester, a derivative of a poly(ethoxylated and/or propoxylated)alcohol, a derivative of a poly(ethoxylated and/or propoxylated)ester, an alkyl alcohol, an alkenyl alcohol, an ester of a polyhydric alcohol, an ether of a polyhydric alcohol, an ester of a polyalkoxylated derivative of a polyhydric alcohol, an ether of a polyalkoxylated derivative of a polyhydric alcohol, a sorbitan fatty acid ester, a polyalkoxylated derivative of a sorbitan fatty acid ester, a betaine, a sulfobetaines, imidazoline derivatives, aminoacid derivatives, lecithins, phosphatides, some amine oxides and sulfoxides and mixtures thereof, present in an amount between about 0.10 % to about 5% weight percent.

A preferred betaine is cocamidopropyl betaine. A preferred alkylglucoside is cocoglucoside. A preferred fluorinated surfactant is DEA C[8- 18] perfluoroalkylethyl phosphate; another preferred fluorinated surfactant is Ammonium C[6-16] perfluoroalkylethyl phosphate, Preferred polyethoxylated fatty alcohols are polyethoxylated stearyl alcohol (21 moles ethylene oxide) and polyethoxylated stearyl alcohol (2 moles ethylene oxide), and a combination of these two.

The compositions may include an antimicrobial agent. The following antimicrobials are offered as non-limiting examples of suitable antimicrobials

for use in the present invention and may include chlorhexidine salt, iodine, a complexed form of iodine, parachlorometaxylenol, triclosan, hexachlorophene, a phenol, behenyl alcohol, a surfactant having a long chain hydrophobic group and a quaternary group, hydrogen peroxide, silver, a silver salt, silver oxide, other quaternary ammonium salts and mixtures thereof.

A preferred antimicrobial agent in the present compositions is chlorhexidine gluconate (CHG) present in an amount between about 0.10 % to about 4.0 % weight percent. Another preferred antimicrobial agent is didecyl dimethyl diamonium chloride in an amount between about 0.05% to 5% weight percent. Another preferred antimicrobial agent is Benzalkonium chloride in an amount between about 0.05% to 5% weight percent. Another preferred anitimicrobial is Behenyl alcohol between 0.05-15% weight percent.

If the amount of ingredients employed is little enough not to leave a tacky feeling after the composition evaporates after single or multiple uses, and this is achieved while maintaining at least 60% v/v ethanol or n-propanol concentration or 70% v/v isopropanol, then the composition would be ideal for use as an alcohol hand sanitizer/disinfectant foamable composition.

The addition of water to the alcohol produces a more stable foam while allowing to reduce the amount of silicone-based surfactant required to foam the product. For example, using 0.5 to 1.0% silicone-based surfactant with a

50 to 60% v/v alcohol water solution produces a stable foam that does not readily collapse and that produces a stable puff that does not fall even when inverted and does not collapse until pressure is applied (such as when rubbed in hands or on over a surface) to provide an alcoholic liquid solution, while

levels of up to 5% are required if the percentage of alcohol used is greater than 65%w/w.

The use of a mild non-irritant surfactant widely used in the cosmetic industry such as cocamidopropyl betaine or a fluorinated surfactant such as DEA C[8-18] perflucroalkylβthyl phosphate or Ammonium C[6-18] perfluoroalkylethyl phosphate as a secondary surfactant is more suitable to prepare the foamable hydroalcoholic composition of the present invention depending on the silicone-based surfactant being used.

In order to stabilize the foam, foam stabilizers, as well as emulsifying ingredients have been tried with good results in allowing the product to be dispensed as a foam even when no propellant and/or pressurized container systems are used.

Examples of compatible foam stabilizers that can optionally be employed include lactic acid esters of monoglycerides, cationic emulsifiers, triquaternized stearic phospholipid complex, hydroxystearamide propyltriamine salts, lactic acid monoglycerides, food emulsifiers such as glyceryl monostearate, Behentrimonium chloride, Cetrimonium chloride, propylene glycol monostearate, glycols, sodium stearoyl lactylate, silicone wax, an encapsulated oil, Microcapsule Mineral Oil. A preferred foam stabilizer used in the present foamable compositions is cetyl betaine. Another preferred foam stabilizer is glycerine. Another preferred foam stabilizer is Cetrimonium chloride and also Behentrimonium chloride.

Examples of moisturizers and/or emollients which may be used in the present formulations include lanolin, vinyl alcohol, polyvinyl pyrrolidone and

polyols selected from the group consisting of glycerol, propylene glycol, glyceryl oleate and sorbitol, cocoglucoside or a fatty alcohol selected from the group consisting of cetyl alcohol, stearyl alcohol, lauryl alcohol, myristyl alcohol and palmityl alcohol, cetyl alcohol, ceteareth 20, and combinations thsrsof, prsssπt in sπ amount up to sbout 5%. i hθ compositions msy include a lipid layer enhancer such as a mixture of alkylglucoside and glyceryl Oleate, or PEG-200 Hydrogenated Glyceryl Palmiate, or Dihydroxypropyl PEG-5 Linoleammonium Chloride or PEG-7 Glyceryl Cocoate.

The compositions are formulated to be dispensed as a foam from an unpressurized dispenser having a dispenser pump for mixing the composition with air and dispensing foam therefrom. Alternatively the composition may be packaged in an aerosol container and dispensed under high pressure conditions.

The present invention is unique in that it can be dispensed as a foam from such manual low pressure dispensing systems as described, however, the composition can alternatively be dispensed under high pressure systems as well.

The composition may include an aerosol propellant in an amount from about 3 to about 20 weight percent of the total composition for pressurized discharge of the foam. The aerosol propellant may include propane, carbon dioxide, butane, dichloro difluoro methane, dichloro tetra fluoro ethane, octafluorocyclo butane; 1 ,1 ,1 ,2-tetrafluoroethane; 1 ,1 ,1 ,2,3,3,3 heptafluoropropane, and 1 ,1 ,1 ,3,3,3,-hexafluoropropane. When stored in a metal container with propellant, the formulation may include a corrosion inhibitor such as sorbic acid, benzoic acid, potassium sorbate and sodium

benzoate, in an amount from about 0.1 to about 5 weight percent of the total composition.

The inventors have very surprisingly discovered that it is possible to produce alcohol foams which include a combination of both the silicone surfactants disclosed herein and flueroεurfactants disclosed in copending

U.S. Patent Application Serial No. 10/952,474, filed: September 29, 2004 and PCT Publication WO 2005/030917 A1 with the resulting foam exhibiting an interesting synergy with respect to the foam quality.

While both types of surfactants in the extremes of the concentrations of alcohol covered produce more and better foam when the alcohol concentration is closer to 40% and produce a lower quality foam that does not last in concentrations higher than 80% it was very interestingly found that the foam quality observed with fluorosurfactants is different from that obtained using silicone based surfactants. With the pumps used for the examples, compositions using fluorinated surfactants are as described as an aereated "quick" breaking foam disappearing within seconds depending on the amount of alcohol and percentage of surfactant used, while with the silicone based surfactants the foam has a distinctive different appearance, it appears to be more dense and sometimes looks more uniform giving the appearance to be "whiter" not necessarily because there might seem to be more bubbles but because the bubbles last longer, they are more stable.

The difference is better observed when comparing side-by-side samples containing the same percentage of alcohol, and while it is evident that when the foam is first dispensed it shows more volume and a "better"

quality appearance if a fluorinated surfactant is used, this visual advantage is observed only during the first few seconds since the foam quite rapidly breaks down to a smaller volume to more resemble the foam obtained with the silicone-based surfactant. The most important difference appears to be how long the foam containing only the εiϋcone-bassd surfactant lasts compared to the time the foam lasts with a foam containing only the fluorinated surfactant.

It should also be noted that one of the main differences in using one surfactant or the other (fluorosurfactants versus silicone surfactants) is the fact that fluorinated surfactants can reduce the surface tension to lower levels than those achieved using silicone-based surfactants alone, therefore compositions with only silicone based surfactants generally need a higher percentage of the silicone based surfactants to achieve a similar result.

A significant advantage to mixing both types of surfactants in the same composition is that the silicone based surfactant gives a longer lasting effect while the fluorinated surfactant has a better tolerance at higher levels of alcohol hence when mixed the combination provides an improvement in foam quality greater than obtaining using either one individually under some conditions.

Combining the surfactants allows the achievement of the desired foaming effect without exceeding solubility limits of either surfactant while at the same time taking advantage of the particular characteristics of the foam differences produced by each one.

The combination of silicone-based surfactants and fluorinated surfactant is of increasing advantage as the alcohol concentration increases, which is desirable to improve the microbiological efficacy.

The following non-limiting examples are set forth to show for the various preferred embodiments and are not in any way to limit the scope of the present invention.

EXAMPLES

Examples 1 through 12 were prepared to illustrate the ability to produce alcohol-based disinfecting formulations which can be dispensed as foams using different surfactants and a solution of water and 50% ethanol. Examples 13 through 16 illustrate increasing concentrations of a silicone- based surfactant to produce foam with 40% ethanol. Examples 17 through 32 show increasing concentrations of ethanol with different silicone-based surfactants to produce foam. Examples 33 through 36 illustrate increasing concentrations of a silicone-based surfactant to produce acceptable foam at 62% ethanol. Examples 37 through 52 illustrate the ability to produce foam using different surfactants and a solution of 70%v/v Isopropanol. All parts and percentages are expressed by weight unless otherwise indicated.

Comparatively, it was also found that for instance, Cocamidopropyl betaine (CAPB) alone even at 40% ethanol and at 3% CAPB, was unable to produce as good results as those with 60%v/v ethanol, and Silicone-based surfactants using much less percentage (less than 1.0%). Cocamidopropyl betaine does not give any acceptable foam above that percentage of alcohol and the lower than 60% v/v alcohol content makes it inadequate for a sanitizing solution. Also the solution left an unacceptable feeling on the skin after the alcohol evaporated (i.e. a soapy sticky feeling) indicating high levels of surfactant. Advantageously, the afterfeel of the present compositions was

not only not soapy but actually pleasant makes the present invention suitable for many different applications.

The following examples were intended to evaluate the foaming ability of different groups of Silicon surfactants with different combinations of ethanol, n-prnny! alcohol and lsopropyl alcohol. They were also designed to assss the effect in the after feel as well as in the foam quality of some emollients and humectants, lipids, and other cosmetic type desired ingredients to be used with a leave-on hand sanitizer product. Some ingredients with antibacterial properties were also added to again evaluate their effect on foam quality and after feel.

Examples 53 to 293 have total alcohol contents from 61 %w/w to 75%w/w. The best foam was achieved with only ethanol as the alcohol, with the next best being the combination Ethanol and n-propyl alcohol using up to 10% n-propyl alcohol. The worst foams were those obtained using only lsopropyl alcohol and/or n-propyl alcohol. Also interesting is the fact that the surfactant that works the best with just ethanol is not the same that works the best with the other 2 alcohols tried. More specifically it was found that the PEG-17-Dimethicone as well as the Bis-PEG/PPG 18/6 Dimethicone work better than the Bis-PEG 12 -Dimethicone with just n-propyl alcohol and/or lsopropyl alcohol. While combining different silicone surfactants if different alcohols are used seems to show a synergy to boost the foam when the addition of another alcohol disrupts the foaming ability of a particular silicone surfactant in the end the preferred silicone for the combination of alcohols emollients and other ingredients lies amongst the Bis-PEG [10-20] Dimethicone silicone surfactants.

Combinations of silicone surfactants with other surfactants were also tried; various experiments showed that although it was possible to find acceptable foam quality improvement when using other surfactants, the soapy after-feel was unacceptable for a leave-on product for many surfactants. However the compositions combining silicone surfactants with fluorosufactants mentioned above showed an improvement that very advantageously allows for the reduction in the percentage of silicone surfactant to optimize percentages in the formulation regarding cost and other efficacy desired outcomes. While some cosmetic ingredients like Cocoglucoside Glyceryl Oleate appear to deteriorate the foam quality when present in the composition, if the after-feel effect is beneficial increasing then the foam quality may be improved by increasing the percentage of surfactant present and/or adding a foam stabilizer to the composition to improve the foam quality. It was also interesting to find that while a higher percentage of silicone surfactant present in the composition has been observed to increase the quality of the foam, the increased amount of silicone surfactant present has to be considerable before an improvement is observed. For example, the foam quality achieved with 1 % was not significantly better with 1.5% but was considerably better with 2% and the foam quality using 3% or 4% was very similar while 5% was much better than just 3%.

The quality of the dispensed foam can be dependant upon the characteristics of the pump mechanism used for dispensing the foam from a bottle. For instance the quality of the foam was better with the smaller shot size of 0.75ml than the bigger shot size of 1.5ml from a pump for the same

size bottle. The shot size is the amount of liquid dispensed when the pump is activated.

From the above examples it can be concluded that they are clearly denoting how the art of foaming alcohol is different form that of foaming water based composition in more than one aspect and that unexpected Outcomes could arise depending on the combination of ingredients desired for the final formulation in combination with the type of foaming device/mechanism to use. Below are some more specific examples for compositions following a formulation to produce alcohol/silicone-surfactant hand/skin sanitizing foamable compositions ; more than one being a foamable disinfecting composition with only alcohol being the only disinfectant ingredient, while other foamable disinfecting compositions use an added antimicrobial such as

Chlorhexidine Digluconate or Didecyl Dimethyl Diammonium Chloride,

Benzalkonium Chloride, Behenyl alcohol, etc. EXAMPLE 294

Alcohol hand sanitizing foamable disinfecting composition

0.01- 5.0 % * silicone-based surfactant (primary surfactant)

0.01 - 1.0% cocoamidopropylbetaine (secondary surfactant)

0.05 - 1.0% cetyl betaine (foam stabilizing agent) 0.10 - 1.5% emulsifier fatty alcohol ROH 16-22 carbons or combination that works well in a final formulation containing

60-70% v/v ethanol

Q. S. water

• Preferably a Bis-PEG-[10-20] dimethicone, a 3-(3-Hydroxypropyl)- heptamethyltrisiloxane, ethoxylated, acetate , a Bis-PEG/PPG 18/6

Dimethicone, acetate, a Polyether-modified polysiloxane or a Polysiloxane betaine, or mixtures thereof.

EXAMPLE 295 Alcohol hand sanitizing foamable disinfecting composition Concentrate 0.1- 5.0 % * a physiologically acceptable silicone-basecl su* lactam* ;(ρrirπary surfactant) 0.001 - 12.0% 1 ,3 Butyleneglycol, 2-Butoxyethanol, or glycerin (foam stabilizing agents)

0.05 - 5.0% cocoglucoside, glyceryl oleate (moisturizers, emollients and the like)

60-70% v/v ethanol, n-propanol, isopropanol or a combination thereof Q.S. water

• Preferably a Bis-PEG-[10-20] dimethicone, 3-(3-Hydroxypropyl)- heptamethyltrisiloxane, ethoxylated, acetate , a Bis-PEG/PPG 18/6 Dimethicone, acetate, a Polyether-modified polysiloxane or a

Polysiloxane betaine, or mixtures thereof.

EXAMPLE 296 Alcohol hand sanitizing foamable disinfecting composition

0.01- 5.0 % * silicone-based surfactant (primary surfactant) 0.01 - 1.0% fluorinated surfactant and or other silicone-based surfactants or mixtures (secondary surfactant/s)

0.05 - 1.0% Cetrimonium Chloride (foam stabilizing agent) 0.05 - 1.0% Behentrimonium Chloride (foam stabilizing agent) 0.10 - 1.5% Dihydroxypropyl PEG-5 Linoleammonium Chloride, Glyceryl Oleate, PEG-200 Hydrogenated Glyceryl Palmate, Behenyl PG-

Trimomium chloride, PEG-7 Glyceryl Cocoate or combination of emollients, lipids, humectants that works well in a final formulation containing 1-10% n-propyl alcohol 80-70% w'v ethanol

Q.S. water

• Preferably a Bis-PEG-[10-20] dimethicone, a 3-(3-Hydroxypropyl)- heptamethyltrisiloxane, an ethoxylated, a Bis-PEG/PPG 18/6 Dimethicone, acetate, a Polyether-modified polysiloxane or a Polysiloxane betaine, or mixtures thereof.

EXAMPLE 297 Alcohol hand sanitizing foamable disinfecting composition

0.01- 5.0 % * silicone-based surfactant (primary surfactant)

0.05 - 1.0% Cetrimonium Chloride (foam stabilizing agent) 0.05 - 1.0% Behentrimonium Chloride (foam stabilizing agent)

0.10 - 1.5% Dihydroxypropyl PEG-5 Linoleammonium Chloride, Glyceryl

Oleate, PEG-200 Hydrogenated Glyceryl Palmate, Behenyl PG- Trimomium chloride, PEG-7 Glyceryl Cocoate or combination of emollients, lipids, humectants that works well in a final formulation containing

1-10% n-propyl alcohol

60-70% v/v ethanol

Q.S. water

• Preferably a Bis-PEG-[10-20] dimethicone, a 3-(3-Hydroxypropyl)- heptamethyltrisiloxane, an ethoxylated, a Bis-PEG/PPG 18/6

Dimethicone, acetate, a Polyether-modified polysiloxane or a Polysiloxane betaine, or mixtures thereof.

EXAMPLE 298 Alcohol hand sanitizing foamable disinfecting composition

0,01- 5.0 % ^* siiicone-based surfactant (primary surfactant)

0.01 - 1.0% fluorinated surfactant and or other silicone-based surfactants or mixtures (secondary surfactant/s)

0.05 - 1.0% Cetrimonium Chloride (foam stabilizing agent) 0.05 - 1.0% Behentrimonium Chloride (foam stabilizing agent) 0.10 - 1.5% Dihydroxypropyl PEG-5 Linoleammonium Chloride, Glyceryl

Oleate, PEG-200 Hydrogenated Glyceryl Palmate, Behenyl PG- Trimomium chloride, PEG-7 Glyceryl Cocoate or combination of emollients, lipids, humectants that works well in a final formulation containing 60-70% v/v ethanol

Q.S. water

• Preferably a Bis-PEG-[10-20] dimethicone, a 3-(3-Hydroxypropyl)- heptamethyltrisiloxane, an ethoxylated, a Bis-PEG/PPG 18/6 Dimethicone, acetate, a Polyether-modified polysiloxane or a Polysiloxane betaine, or mixtures thereof.

EXAMPLE 299 Alcohol hand sanitizing foamable disinfecting composition

0.01- 5.0 % * silicone-based surfactant (primary surfactant) 0.05 - 1.0% Cetrimonium Chloride (foam stabilizing agent) 0.05 - 1.0% Behentrimonium Chloride (foam stabilizing agent)

0.10 - 1.5% Dihydroxypropyl PEG-5 Linoleammonium Chloride, Glyceryl

Oleate, PEG-200 Hydrogenated Glyceryl Palmate, Behenyl PG- Trimomium chloride, PEG-7 Glyceryl Cocoate or combination of emollients, lipids, humectants that works well in a final s formuisiJon oontsinlnc!

60-70% v/v ethanol

Q.S. water

• Preferably a Bis-PEG-[10-20] dimethicone, a 3-(3-Hydroxypropyl)- heptamethyltrisiloxane, an ethoxylated, a Bis-PEG/PPG 18/6 10 Dimethicone, acetate, a Polyether-modified polysiloxane or a

Polysiloxane betaine, or mixtures thereof.

EXAMPLE 300

Chlorhexidϊne gluconate (CHG) & alcohol hand sanitizing foamable disinfecting composition

Ϊ5 Formulation 294, 295, 296, 297, 298 or 299 added with

0.50 - 4.0% Chlorhexidine Gluconate (CHG)

EXAMPLE 301

Didecyl Dimethyl Diammonium Chloride & alcohol hand sanitizing foamable disinfecting composition

20 Formulation 294, 295, 296, 297, 298 or 299 added with

0.01 - 5.0% Didecyl Dimethyl Diammonium Chloride

EXAMPLE 302

Benzalkonium Chloride & alcohol hand sanitizing foamable disinfecting composition

Formulation 294, 295, 296, 297, 298 or 299 added with 0.01 - 5.0% Benzalkonium Chloride

EXAMPLE 300

Behenyl Alcohol & alcohol hand sanitizing foamable disinfecting composition

Formulation 294, 295, 296, 297, 298 or 299 added with 0.01 - 5.0% Behenyl Alcohol

The process to prepare the compositions of the present invention described herein is straightforward since most of the ingredients are liquid. When wax type ingredients are to be used, they can be incorporated by warming up to 40-45 ⁰ C preferably to the water portion while mixing and then allowing it to cool down or they could be added in "cold", at room temperature to the alcohol before any other ingredient and mixed until completely incorporated before adding the rest of the ingredients according to the composition.

Active ingredients may be pre-dissolved into the water first, a process that will be well known to anyone skilled in the art. If a specific formulation cannot be adjusted to give the desired quality of foam with the preferred percentages of the different constituents, the characteristics of the dispensing mechanism may be modified to improve foam quality, for example the type and characteristics of the foaming pump, such as changing the air/liquid ratio, screen sizes at the nozzle, to mention a few, can be adjusted in ways which will be apparent to those skilled in the art.

The compositions described herein provide improved alcohol based disinfecting products over commercially available compositions with high concentrations of alcohol, as well as the fact they are able to foam without the use of propellants or pressurized containers, although it will be appreciated that using propellents may in some cases Improve the quality of the resulting foam.

Depending on the alcohol concentration and the application of the particular composition the foam produced can widely vary, being at the high end of a relatively fast breaking foam variety which is stable enough to be thoroughly spread onto the skin without undue waste or effort.

The present formulations may be first made as a concentrate with only some of the constituents which can be shipped and then constituted with the remaining constituents. For example, the concentrate can include a) the effective silicone-based surface active agent for wetting and foaming present in an amount of at least 0.01 % weight percent of the total composition 0.01to about 15.0 %, a foam stabilizing agent including at least from about 0.01 to about 10.0%, and any one of moisturizers, emollients and combinations thereof present in a range from about 0.05% to about 5.0%; and water.

The composition concentrate can then be constituted as an alcohol disinfecting composition by adding a) an alcohol C-M, or mixtures thereof, present in an amount between about 60 % v/v to about 80% v/v of the total composition; and b) water present in an amount to balance the total composition to 100% weight percent.

Due to the nature of the base composition with respect to the alcohol concentration and the quality of the ingredients, an advantageous application

for the present invention is as an alcohol skin/hand disinfectant composition for a foamable product, examples of which are described above. Nevertheless, the present invention lends itself to the preparation of a wide variety of products for disinfecting applications, and it is to be understood that other embodiments may be uti!i~eri and th«t chθnαθs may be made without departing from the scope of the invention.

Consequently, it is intended that the claims be interpreted to cover such modifications and equivalents. To note a few, the following products may be produced using the alcohol/silicone-surfactants: medicated foams, sunscreen foams, hand cream foams, brush-less shaving cream foams, shower or bath oil foams, dry hair shampoo foams, make-up remover foams, analgesic foam rubs, hair grooming foams and antiperspirants hair cleaning foam, antiperspirant foam, hair conditioner foams.

As used herein, the terms "comprises", "comprising", "includes" and "including" are to be construed as being inclusive and open ended, and not exclusive. Specifically, when used in this specification including claims, the terms "comprises", "comprising", "includes" and "including" and variations thereof mean the specified features, steps or components are included. These terms are not to be interpreted to exclude the presence of other features, steps or components.

The foregoing description of the preferred embodiments of the invention has been presented to illustrate the principles of the invention and not to limit the invention to the particular embodiment illustrated. It is intended that the scope of the invention be defined by all of the embodiments encompassed within the following claims and their equivalents.

REFERENCES CITED U.S. PATENT DOCUMENTS

2,054,9899/1936 Moore 167/58

3,131 ,1534/1964 Klausner 252/305

3,962,1506/1976 Leonard et al 252/542

4,440,6534/1984 James et al 252/8.55

FMR7 950 12/1992 Lins .424/47

4^956,170 09/1990 Lee 514/772.1

5,629,0065/1997 Minn et al 424/405

5,906,8085/1999 Osborne, et al 424/43

5,928,9937/1999 lngegard ..504/116

5,951 ,993 09/1999 Scholz et al 424/405

6,090,395 07/2000 Asmus et al 424/401

6,610,315 08/2003 Scholz et al 424/415

6,623,744 09/2003 Asmus et al 424/401

6,562,360 05/2003 Scholz et al 424/405

OTHER PUBLICATIONS

Myers, Drew; "Surfactant Science and Technology", second edition, Drew Myers.VCH Publishers, New York, 1992

Examples 1-6

Amount Ingredients Ex. 1 Ex. 2 Ex. 3 Ex. 4 Ex. 5 Ex. 6

Ethanol. 50.00 50.00 50.00 50.00 50.00 50.00 Silicone-based surfactant 0.50 Cocamidopropyl betaine (1) 8.00 Alkylglucoside (2) 8.00 Alkylglucoside (3) 8.00 Glycomul L 8.00 Sorbitan Sesquioleate 8.00 Purified Water 49.50 42.00 42.00 42.00 42.00 42.00

Total % 100.00 100.00 100.00 100.00 100.00 100.00

(1) Amphoteric, (2) Nonionic, (3) Anionic

Examples 7-12

Amount Ingredients Ex. 7 Ex. 8 Ex. 9 Ex. 10 Ex. 11 Ex. 12

Ethanol 50.00 50.00 50.00 50.00 50.00 50.00

Poiysorbate 20 8.00

Polyoxyethylene Sorbitan Monooleate 8.00

Sorbitan Monooleate 8.00

Cocamidopropyl betaine & sodium caproyl lactate 8.00

Cocamidopropyl hydroxysultaine 8.00

Sodium Cocoamphoacetate 8.00

Purified Water 42.00 42.00 42.00 42.00 42.00 42.00

Total % 100.00 100.00 100.00 100.00 100.00 100.00

Examples 13-16

Amount Ingredients Ex. 13 Ex. 14 Ex. 15 Ex. 16

Ethanol 40.00 40.00 40.00 40.00

Bis-PEG-20 dimethicone 0.01

3-(3-Hydroxypropyl)-heptamethyitrisiloxane,ethoxylated ₎ acetate 0.01

Polyether-modified polysiloxane 0.01

Polysiloxane betaine 0.01

Purified Water 59.99 59.99 59.99 59.99

Total % 100.00100.00 100.00 100.00

Examples 17-20

Amount Ingredients Ex. 17 Ex. 18 Ex. 19 EK. 20

Ethanol 40.00 50.00 60.00 75.00 Bis-PEG-20 dimethicone ^" 0.01 0.01 0.01 8.00 Purified Water 59.99 49.99 39.99 17.00

Total % 100.00 100.00 100.00 - 100.00

W

Examples 21-24

Amount Ingredients Ex. 21 Ex. 22 Ex. 23 Ex. 24

Ethanol 40.00 50.00 60.00 75.00 Polysiloxane betaine 1.0 1.0 1.0 8.00 Purified Water 59.00 49.00 49.00 17.00

Total % 100.00 100.00 100.00 100.00

Examples 25-28

Amount Ingredients Ex. 25 Ex. 26 Ex. 27 Ex. 28

Ethanol 40.00 50.00 60.00 75.00 Polyether-modified polysiloxane 1.0 1.0 1.0 1.0 Purified Water 59.00 49.00 39.00 24.00

Total % 100.00 100.00 100.00 100.00

— - Examples 29-32

Amount Ingredients Ex. 29 Ex. 30 Ex. 31 Ex. 32

Ethanol 40.00 50.00 60.00 75.00 3-(3-Hydroxypropyl)-heptamethyltrisiloxane, ethoxylated, acetate 0.5 0.5 0.5 10.00 Purified Water 59.5 49.50 39.50 15.00

Total % 100.00 100.00 100.00 100.00

Examples 33-36

Amount Ingredients Ex. 33 Ex. 34 Ex. 35 Ex. 36

Ethanol 62.00 62.00 62.00 62.00 Bis-PEG-20 dimethicone 0.50 1.00 2.0 5.00 Purified Water 37.50 37.00 36.00 33.00

Total % 100.00 100.00 100.00 100.00

Examples 37-42

Amount Ingredients Ex. 37 Ex. 38 Ex. 39 Ex. 40 Ex. 41 Ex. 42

70%v/v lsopropanol 99.90 92.00 92.00 92.00 92.00 92.00 Silicone-based surfactant 0.10 Cocamidopropyl betaine (1) 8.00 Alkylglucoside (2) 8.00 Alkylglucoside (3) 8.00 Glycomul L 8.00 Sorbitan Sesquioleate 8.00

Total % 100.00 100.00 100.00 100.00 100.00 100.00

(1 ) Amphoteric, (2) Nonionic, (3) Anionic

Examples 43-48

Amount Ingredients Ex. 43 Ex. 44 Ex. 45 Ex. 46 Ex. 47 Ex. 48

70%v/v lsopropanol 92.00 92.00 92.00 92.00 92.00 92.00

Polysorbate 20 8.00

Polyoxyethylene Sorbitan Monooleate 8.00

Sorbitan Monooleate 8.00

Cocamidopropylbetaine & sodium caproyl lactate - 8.00

Cocamidopropyl hydroxysultaine 8.00

Sodium Cocoamphoacetate 8.00

-4

Total % 100.00 100.00 100. 00 100 .00 100 .00 100.00

Examples 49-52

Amount Ingredients Ex. 49 Ex . 50 Ex. 51 Ex. 52

70%v/v lsopropanol 99.00 99.00 99.00 99.00

Bis-PEG-20 dimethicone 1.0

3-(3-Hydroxypropyl)-heptamethyltrisiloxane, ethoxylated, acetate 1.0

Polyether-modified polysiloxane 1.0

Polysiloxane betaine 1.0

Total % ^: 100.00 100.00 100.00 100.00

The solutions prepared, were evaluated as to whether foam was produced or not and if so, then the foam produced was described as follows:

xample Foam Produced Foam Evaluation/Description/Characteristics

Ex. 1 Yes Very good stable stiff puff creamy and soft lasts a long time

Ex. 2 No Just Very Wet Bubbles produced lasting <10 seconds

Ex. 3 No

Ex. 4 No

Ex. 5 No

OO Ex. 6 No Just Very Wet Bubbles produced lasting <7 seconds

Ex. 7 No Just Very Wet Bubbles produced lasting <10 seconds

Ex. 8 No

Ex. 9 No Just Very Wet Bubbles produced lasting <10 seconds

Ex. 10 No

Ex. 11 No

Ex. 12 No

Ex. 13 Yes Quick fast breaking foam lasts more than a minute

Ex. 14 Yes Very good puff creamy and soft lasts minutes

Ex. 15 Yes Very good puff creamy and soft lasts minutes

Ex. 16 Yes Quick fast breaking foam lasts more than a minute

Ex. 17 Yes Very good puff creamy and soft lasts minutes

Ex. 18 Yes Good puff creamy and soft lasts minutes

Ex. 19 Yes Quick fast breaking foam lasts more than a 10secs

Ex. 20 Yes

Ex. 21 Yes Runny watery foam which lasts more than 45secs

Ex. 22 Yes Quick fast breaking foam lasts more than a IOsecs

Ex. 23 Yes Runny watery foam which lasts more than 20secs

Ex.24 Yes

Ex.25 Yes Runny watery foam which lasts more than 20secs

Ex.26 Yes Runny foam which lasts more than 20secs

Ex.27 Yes Quick fast breaking foam lasts more than a 45secs

Ex.28 No Quick fast breaking foam lasts more than a 45secs

Ex.29 Yes Very good creamy and soft lasts more than a minute

Ex.30 Yes Good creamy and soft lasts more than a minute

Ex.31 Yes Quick fast breaking foam lasts more than a 45secs

Ex.32 No

Ex.33 No Quick fast breaking foam lasts more than a minute

Ex.34 No Good creamy and soft lasts more than a minute

Ex.35 No Very good creamy and soft lasts more than a minute

Ex.36 No Very good creamy and soft lasts minutes

Ex.37 Yes Quick fast breaking foam lasts more than a 20secs

Ex.38 No

Ex.39 No

Ex.40 No

Ex.41 No

Ex.42 No

Ex.43 No

Ex.44 No

Ex.45 No

Ex.46 No

Ex.47 No

Ex.48 No

Ex.49 Yes Runny watery foam which lasts more than a 45secs

Ex.50 Yes Runny watery foam which lasts more than a 45secs

Ex.51 Yes Runny watery foam which lasts more than a 45secs

Ex.52 Yes Runny watery foam which lasts more than a 45secs

Examples 53-63

Examples 64-73

Example 74-84

Example 85-94

Examples 95-115

Examples 116-136

Examples 137-156

Examples 157-167

Examples 168-177

4- -4

Examples 178-188

4-

00

Examples 189-198

4-

Examples 199-219

O

Examples 220-230

Examples 231-240

Examples 241-251

K)

Examples 252-261

Examples 262-272

Examples 273-282

Examples 283-293