A swing analysis system includes a housing having an upper surface and a ball support mounted to the upper surface. A first array of optical sensors is mounted in the upper surface on a first side of the ball support, and a second array of optical sensors is mounted in the upper surface on a second side of the ball support, opposite the first array of sensors. A third array of optical sensors in mounted in the upper surface, with the sensors positioned around the ball support. A controller is coupled to each sensor of the three arrays of sensors for receiving output signals therefrom. The controller monitors the output signals for change in state events and creates data files containing a sequence of events with associated timestamps. The computer is programmed to use the data files to calculate swing path angle, club head speed, club head angle, club head lateral alignment with respect to the ball support, and club head height of an implement (e.g., a golf club) swung over the housing. The system can also be provided with at least one tower attached to a side of the housing and extending above the upper surface. The tower includes additional sensors that are used by the computer to calculate club head loft angle. The computer can also calculate an effective club head speed from the measured values of club head speed, swing path angle, club head lateral alignment and club head angle.

1. Field of the Invention
The present invention relates to devices to aid in analyzing the swing or stroke associated with certain athletic activities. More particularly, the present invention relates to a sensor-based system to detect the path and orientation of the component swung, and a computer system to analyze the data obtained from the sensing system. Still more particularly, the present invention is well suited to the analysis of the swing of a golf club but is not limited thereto.
2. Description of the Prior Art
There are many ways for participants in athletic activities to improve their skills in order to improve performance. One obvious way is to practice the skills and strategies associated with the particular activity. In addition, there exist devices and systems that a sport participant can use to make critical evaluations of the techniques and mechanics associated with the particular sport. For example, football and baseball players can review videotapes of their efforts during the course of a game or practice. Based on flaws detected during the review, the participant can adjust mechanics and/or strategies. However, in certain athletic activities, particularly those involving the use of an implement moving at a high rate of speed, it can be difficult to assess accurately any flaws in the effort Such activities include, but are not limited to, tennis, baseball (bat swinging), ice hockey, field hockey, lacrosse, and golf.
In the sport of golf in particular, there have been a number of advances in golf club swing analysis. Initially, an individual mentor or coach would observe a player swing a club to hit a ball and then critique the swing. While a skilled observer can detect flaws in a swing, the human eye may not be able to make an assessment that is complete and completely correct. Moreover, the expense associated with a personal coach can be prohibitive for many participants. Given the wide popularity of golf, there are many individuals unable to take advantage of the expertise of a skilled swing observer. Therefore, when the portable video camera became commonly available, it provided a convenient method for local golf course professionals and other golf teachers to observe more players"" swings more critically. Further, it enabled individual players to record and assess their own swing. However, as with observation by a skilled teacher, it is difficult for an individual to analyze completely and completely accurately the flaws in his or her own swing. Additionally, even skilled observers cannot assess a swing completely based on videotape.
More recently, systems have been described to aid in the analysis of a golf swing. For example, U.S. Pat. No. 5,718,639 issued to Bouton describes a golf club swing sensing system and a method of playing a simulated golf game. In particular, Bouton provides a mat with a plurality of photodetectors used to record the passage of a reflector applied to the golf club head. The output of the detectors is transmitted to a computer system that produces a video representation of the swing. Alternatively, U.S. Pat. No. 5,474,298 issued to Lindsay describes a swing analyzer that includes a magnet set applied to a club head and an inductive array positioned in the vicinity of the club head path. As the magnets pass over (or do not pass over) the inductive array, electrical signals are or are not transmitted to an analyzer. The signal set is then converted into an indication of swing path and that detected path is compared to an idealized path. The user is then informed about swing deviation and can work to adjust the swing.
While the prior systems appear to improve upon the relatively inaccurate method of swing analysis by videotape, they provide information on a limited number of swing parameters. As a result, these devices fail to provide a complete assessment of the golf swing. In particular, the prior systems do not completely assess the orientation of the club head at the point of impact.
Therefore, it would be desirable to have a swing analysis system that was able to assess a large number of swing or club head parameters.
The above-mentioned need is met by the present invention, which provides a swing analysis system comprising a housing having an upper surface and a ball support mounted to the upper surface. A first array of optical sensors is mounted in the upper surface on a first side of the ball support, and a second array of optical sensors is mounted in the upper surface on a second side of the ball support, opposite the first array of sensors. A third array of optical sensors in mounted in the upper surface, with the sensors positioned around the ball support. A controller is coupled to each sensor of the three arrays of sensors for receiving output signals therefrom. The controller monitors the output signals for change in state events and creates data files containing a sequence of events with associated timestamps. A computer is connected to the controller for receiving the data files. The computer is programmed to use the data files to calculate swing path angle, club head speed, club head angle, club head lateral alignment with respect to the ball support, and club head height of an implement swung over the housing. The system can also be provided with at least one tower attached to a side of the housing and extending above the upper surface. The tower includes additional sensors that are used by the computer to calculate club head loft angle. The computer can also calculate an effective club head speed from the measured values of club head speed, swing path angle, club head lateral alignment and club head angle.
The present invention and its advantages over the prior art will become apparent upon reading the following detailed description and the appended claims with reference to the accompanying drawings.


The invention relates to specific aqueous compositions comprising alkoxylated sugar esters and their use as a softener. The alkoxylated sugar esters are characterised by a molar ratio of alkoxy units to hydroxy groups of the unmodified sugar from 1:4 to 3:1, a molar ratio of ester groups to hydroxy groups of the unmodified sugar from 0.25 to 0.70, and an HLB value below 8, preferably from 1-3. Preferably the alkoxylated sugar esters are combined with performance boosters selected from cationic and non-ionic compounds to increase their softening performance.

The present invention relates to the use of sugar derivatives as a softener in liquid aqueous softener compositions and to liquid aqueous softening compositions comprising at least one sugar derivative and at least one performance booster.
Such use and compositions are known from WO 98/16538, where it is disclosed to use a combination of i) esterified or etherified sugar compounds comprising at least 2 or more ester or ether groups and containing at least 35% tri or higher esters and ii) a deposition aid, preferably a fabric softening quaternary ammonium compound.
However, improved aqueous sugar-based liquid softening compositions that combine excellent dispersion stability with a good softening performance are desired. Because of their non-ionic sugar ester structure, the ecotoxicity of these softening compounds is superior to the ecotoxicity of conventional (fabric) softeners. Preferably, softening compositions are developed which comprise a sugar moiety with inherent biodegradability and have a softening performance close to that of conventional (fabric) softeners and a dispersion stability superior to that of the compositions of WO 98/16538.
Extensive research on this well-developed subject has led to surprising results. More specifically, it was observed that when a specific type of sugar derivative is used, most of the known problems associated with current sugar-based (fabric) softeners could be overcome.
Accordingly, the current invention relates to the use of alkoxylated sugar esters with:
a molar ratio of alkoxy groups in the alkoxylated sugar ester to hydroxy groups of the starting sugar from 1:4 to 3:1,
a molar ratio of ester groups in the alkoxylated sugar ester to hydroxy groups of the sugar that was used from 0.25 to 0.70, and
a HLB value below 8,
in aqueous liquid softening compositions. Preferably, the alkoxylated sugar esters have a HLB value below 5, more preferably below 3.5, and most preferably below 3, while a preferred use is in one or more aqueous wash or rinse cycles.
In a second embodiment, the invention relates to aqueous liquid softening compositions comprising such alkoxylated sugar esters. Such compositions may be in the form of dispersions of said alkoxylated sugar esters, in the form of clear solutions of the alkoxylated sugar esters, or in a form wherein one or more of the alkoxylated sugar esters are partially dispersed and/or partially dissolved. The term aqueous means that the composition contains water. Usually, the liquid solvent/dispersing medium is predominantly water. However, in compositions according to the invention, more or less of the water may be replaced by other suitable solvents/diluents, such as alcohols, diols, and polyols. Preferably, such additional solvents/diluents are acceptable from an environmental point of view.
In respect of the HLB value of these compounds, the result of the HLB test as described below is decisive, because it has been observed that the results of calculus as used in the industry to predict the HLB value of a compound often are erroneous.
It is noted that conventional fabric softeners typically are based on hydrophobic quaternary ammonium compounds, mostly of the dialkyl ammonium type. For an indication of hydrophobic compounds, reference is made to E. Jungermann, ed., Cationic Suffactants (Marcel Dekker, 1970). The micelles formed by conventional (fabric) softening compounds in the washing water typically are adsorbed for 85 to 95% by the negatively charged textile fibres within 1 to 3 minutes. Such softeners are known to be unsuitable as detergents and may even act as soil fixatives. Hence they are often added to textiles after the washing step.
It is further noted that non-ionic compounds may also exhibit a softening performance, albeit one inferior to that of conventional dialkyl quaternary ammonium-based fabric softeners. WO 98/16538 discloses sugar esters, which are non-ionic compounds, with advantageous biodegradation properties when compared to conventional quaternary softeners. Until now, it has generally been believed that sugar-derived products typically have good biodegradation properties but insufficient dispersing properties and insufficient softening performance.
Furthermore, it is noted that, in contrast to the process to make typical sugar ester compounds, the process to make the alkoxylated sugar esters according to the invention does not necessarily make use of additional emulsifiers. Compared to the process to make conventional sugar ester compounds, the process according to the invention does not require the use of high-boiling, difficult to remove, a-protic solvents like DMSO and DMF, and again there is no need to use additional emulsifiers and/or catalysts. Hence, the alkoxylated sugar esters of the invention can be prepared in such a way as to make them less contaminated with emulsifiers and solvent than the conventional sugar ester compounds, with all associated advantages.
Alkoxylated sugar esters are known compounds. Their production is disclosed, for example, in GB 982,078, DE-AS-1 277 237, and DE-AS-1 934 540. In GB 982,078 the products are disclosed to be useful as plasticiser, foam stabiliser, emulsifier, dispersing agent, levelling agent, wetting agent, and as a raw material for plastics. According to DE-AS-1 277 237, they are compounds with optimal surface-active properties, while DE-AS-1 934 540 discloses that the products have good biodegradation properties and are useful as a raw material for laundry detergent compositions, in particular as an emulsifier, detergent, solubiliser and/or defoamer. Hence, a wide range of uses of these compounds has been proposed, including those in the laundry detergent field. The products, however, so far have only been promoted as a mere detergent, meaning that they are used to remove deposits from the surface of the textiles to be laundered, which is the purpose of most non-ionics in use today. Typically, detergents have a HLB value of 12-14 (see, for instance, H. E. Garrett, Surface Active Chemicals (Oxford: Pergamon Press, 1972), p. 56) and a corresponding high water solubility.
It is noted that conventional hydrophobic fabric softeners were often applied after the washing and rinsing steps of the laundry process, e.g., by spraying a solution of such conventional agents onto the fabric during or after drying, or by adding a substrate impregnated with such a conventional softener to the fabric during the drying step. Such impregnated substrates are also known as dryer sheets, since they are typically sheets of an impregnated pliable material that are added to the fabric when it is being dried. U.S. Pat. No. 5,376,287, for example, discloses the use of such dryer sheets wherein the heat of the drying cycle liberates the softeners for redistribution over the fabric being dried. Accordingly, the known products are highly ethoxylated and/or just slightly esterified with (hydrophobic) acids, or they are in the solid form, viz. in dryer sheet form, which is not according to the present invention.
Surprisingly, it has now been found that the aqueous alkoxylated sugar ester compositions according to the invention can be used as a softener in, inter alia, laundry applications. This means they can be added during a rinse and/or washing cycle. Typically, the aqueous compositions will contain 0.5 to 50, preferably 2.5 to 40, more preferably 5 to 30 per cent by weight of the total composition of said alkoxylated sugar esters.
Preferred alkoxylated sugar esters for use in said compositions have a HLB value of less than about 5, more preferably less than 3.5, and most preferably of 1 to 3. In order to obtain an optimum performance, they are preferably combined with a performance booster selected from the group consisting of cationic, anionic, amphoteric, and non-ionic surfactants, as known in the art. The group of performance boosters includes betaines, amines, water-soluble salts of amines, amine-oxides, and combinations thereof. Such boosters are typically present in an amount of 0 to 75, preferably 0.5 to 50 per cent by weight of the total composition according to the invention.
Preferred water-soluble salts of amines are salts of tertiary amines, more preferably those of tertiary amines with one C16-18 hydrocarbyl group, and even more preferably the neutral salts thereof, with the amine being neutralised with organic or inorganic acids, such as citric acid or hydrochloric acid. Preferred amines, or salts thereof, that are suitable for use according to the invention include stearyl dimethyl amine (Armeen(copyright) 18 ex Akzo Nobel), tallow bis(2-hydroxyethyl) amine (Ethomeen(copyright) T/12 ex Akzo Nobel), and salts thereof. Preferred amine-oxides that can be used as a performance booster according to the invention are amine-oxides comprising one C16-18 hydrocarbyl group, such as tallow bis(2-hydroxyethyl) amine-oxide (Aromox(copyright) T/12 ex Akzo Nobel). Preferred amphoterics include stearyl dimethyl betaine and tallow amphopolycarboxy glycinate (Ampholak(copyright) 7TX ex Akzo Nobel). Preferred anionic compounds include fatty alcohol sulfates, fatty alcohol ether sulfates, olefin sulfonates, and fatty acid salts (soaps). Typical examples of such compounds are sodium C12-18 alkyl sulfate (Elfan(copyright) 280 D ex Akzo Nobel), sodium C12-15 alkyl ether (2.5) sulfate (Elfan(copyright) NS 252 S ex Akzo Nobel), sodium C14-16 olefin sulfonate (Elfan(copyright) OS 46 ex Akzo Nobel), and sodium stearate. However, preferably the performance booster is a cationic or non-ionic surfactant, as described below.
If the alkoxylated sugar esters are used together with one of the above-mentioned performance boosters, they are deposited, e.g., on a textile fabric, rather than remaining in the water phase and acting as a detergent. However, the dispersion of the alkoxylated sugar esters is more stable than that of corresponding non-alkoxylated sugar esters and therefore exhibits advantages with respect to storage stability and softening performance. Furthermore, the use during the washing/rinse cycle ensures a good distribution of the softener over the fabric, and the amount of softener can be easily controlled. It makes the use of dryer sheets superfluous.
Even more surprisingly, it has now been found that the improved dispersion behaviour of the alkoxylated sugar ester is accompanied by a good softening performance. Sometimes the softening performance of the ethoxylated sugar ester is even better than that of the sugar ester itself. This cannot be explained from theory, because theory predicts that alkoxylation with hydrophilic epoxides like ethylene oxide leads to a decrease of the softening performance due to the expected increase in HLB value. Furthermore, the excellent softening performance of combinations of alkoxylated sugar esters and one or more performance boosters is considered to be remarkable. Upon further investigation, it was observed that, contrary to theory, the alkoxylation of sugar esters leads to a decrease of the HLB value of the compounds. The most remarkable drop within the group of ethoxylated sugar esters was observed for compounds with a low degree of ethoxylation. Upon introduction of further ethylene oxide molecules, the HLB value again increases as expected, but often the HLB value will remain below the HLB value of the corresponding non-ethoxylated compound. Although this may explain the good softening performance of these compounds, it makes the improved dispersion stability the more surprising, because a more hydrophobic compound is expected to be less stable when dispersed in an aqueous phase.
The alkoxylated sugar esters to be used according to the invention can be prepared in well-known ways. For instance, they can be prepared by the process of GB 982,078, where an etherified sugar derivative is reacted with a fatty acid ester, optionally in the presence of a solvent, using sodium methylate or potassium carbonate as a catalyst at temperatures of 90-155xc2x0 C. A similar process is described in DE-AS-1 934 540, where a sugar compound is first ethoxylated at 120xc2x0 C. and subsequently esterified using a triglyceride at 100xc2x0 C. and a potassium carbonate catalyst or a fatty acid at 180xc2x0 C. with hydrochloric acid as the catalyst. However, they can also be prepared according to DE-AS-1 277 237, where a sugar compound is reacted in one step with ethylene oxide and a C6-30 fatty acid at a temperature of 70-200xc2x0 C. and a pressure of 1-50 atm in the presence of a C1-18 alcohol. Furthermore, the process may consist of the steps where the sugar compound is first esterified and subsequently etherified. Optionally, a solvent is used in these processes and if the conditions are chosen properly, also an enzyme may be used to catalyse the esterification reaction as in, for instance, EP-A-0 882 798. It is preferred to produce the alkoxylated sugar esters according to the invention by first alkoxylating the sugar compound, followed by esterification of the intermediate. If the use of a solvent is desired during the alkoxylation step, e.g., to facilitate the contacting of the reactants and more efficient reaction heat removal, then it is preferred to use a solvent selected from the group consisting of water, glycerol, glycols, lower (preferably aliphatic) alcohols, and sorbitol. In a most preferred embodiment, a saturated solution of sugar in water is alkoxylated and subsequently, after removal of the water, esterified. It is to be noted that the term xe2x80x9cesterificationxe2x80x9d as used herein comprises both direct esterification processes, e.g., by reaction of acid and alcohol, and transesterification processes, e.g., the reaction of an alcohol with a triglyceride.
If the alkoxylated sugar esters are to be used in softening compositions that do not comprise performance boosters, then it is preferred to use alkoxylated sugar esters with a HLB value of less than 5, more preferably of less than 3, and most preferably of less than 2, in order to obtain a good softening performance. Typically, the HLB value is greater than 1.
The sugar compounds that can be used according to the invention are mono- and disaccharides, reduction products thereof wherein the aldehyde or ketone group has been reduced to an alcohol moiety, dehydrated sugar derivatives, and mixtures of such compounds. Preferred sugar compounds have at least 4 hydroxy groups. Preferred monosaccharides are glucose, fructose, galactose, ribose, mannose, xylose, arabinose, and sorbose. Preferred disaccharides are maltose, sucrose, cellobiose, and lactose. Sucrose is the most preferred sugar compound used in the invention. Reduced saccharides include, but are not limited to, sorbitol, mannitol, xylitol, and erythritol. Sorbitol is a particularly preferred reduced sugar compound with 6 hydroxy groups. Of the less preferred dehydrated sugar derivatives, sorbitan is preferred, a compound with 4 hydroxy groups.
In order to obtain preferred alkoxylated sugar esters, the sugars are alkoxylated so that a molar ratio of alkoxy units in the final alkoxylated sugar ester to hydroxy groups of the original sugar molecule is from 1:4 to 2:1, more preferably from 1:4 to 3:2, and most preferably from 1:3 to 2:3. The alkoxylation reaction is preferably carried out by reacting epoxides with the sugar compound. Because alkoxylation of the various hydroxy groups of the starting sugar (or of the esterified sugar) will occur in a statistical fashion, as is known in the art, the above-mentioned ratio of alkoxy units to hydroxy groups is a ratio that may differ for each particular molecule but is on average within the specified range. Epoxides that can be used include, but are not limited to, ethylene oxide, propylene oxide, 1-butylene oxide, cis-2-butylene oxide, trans-2-butylene oxide, and combinations thereof. Preferred epoxides to make the alkoxylated sugar esters according to the invention are ethylene oxide, propylene oxide, and combinations thereof. If a combination of epoxides is used, this can be done by using a mixture of the respective epoxides during one and the same alkoxylation step, or by using different epoxides subsequently. The order in which the different epoxides are used is not restricted and the same epoxide can be used twice. By varying the degree of alkoxylation and/or the types and sequence of epoxides used, the skilled person will know how to adapt the HLB value of the resulting softener, if so desired.
The ester functions in the alkoxylated sugar esters of the invention typically are derived from saturated or unsaturated, linear or branched C8-22 fatty acids, optionally substituted with, e.g., one or more hydroxy groups. Preferred fatty acids used in making the alkoxylated sugar esters of the invention include coconut, palm, palm kernel, soya, oleic, tallow, rapeseed, canola, behenic, eruca fatty acids, and mixtures thereof. Preferably a fatty acid mixture is used comprising at least 50 per cent by weight (%w/w) of C16-18 fatty acids. The acids may be used as such in a conventional direct esterification process, but also derivatives can be used, such as the corresponding acid chlorides or (mixed) anhydrides. In transesterification reactions typically a fatty acid ester is used. In such transesterification reactions the methyl, ethyl, and/or glycerol esters of the acids are preferably used. Most preferred are mono-, di- and/or triglycerides of the acids. In order to arrive at softening compounds with the desired HLB value, the skilled person can vary the degree of esterification and the type of, optionally substituted, fatty acid in well-known ways. Nevertheless, the sugar compounds, or alkoxylated sugar compounds, are to be esterified with said acids such that the formed alkoxylated sugar ester has a molar ratio of ester groups to the OH groups of the original sugar compound from 0.25 to 0.70, meaning that 25-70% of all hydroxy groups, or etherified hydroxy groups, are esterified. Preferably, said ratio of ester to OH groups is from 0.30 to 0.65, white the most preferred ratio is from 0.35 to 0.60. Because such non-stoichiometric esterification reactions will not lead to one well-defined product, the specified ratio is the ratio as found on average in the resulting alkoxylated sugar ester.
The alkoxylated sugar esters with a HLB value of less than 8 and obtained as described above, when used in aqueous solutions, combine a good dispersion stability with a good softening performance, especially compared to the other known sugar derivatives. However, in a further embodiment of the invention, these alkoxylated sugar esters are combined with performance boosters to obtain a dispersion stability and a softening performance comparable with those of the best present-day softeners available.
The preferred performance boosters are selected from cationic surfactants and hydrophobic non-ionic compounds. The cationic surfactants can be of the conventional water-dispersible type, particularly quaternary dialkyl ammonium compounds, such as di(hydrogenated tallow) dimethyl ammonium chloride, methyl di(hydrogenated tallowamidoethyl) (2-hydroxyethyl) ammonium methylsulfate, 1-methyl 1-tallowamido-ethyl 2-tallow imidazolinium methylsulfate, and quaternary diesteralkyl ammonium salts, such as di(hydrogenated tallowoyloxyethyl) dimethyl ammonium chloride, 2,3-bis(hydrogenated tallowoyloxy)-propane trimethyl ammonium chloride, polyol ester quats as described in EP-A-0 638 639, and di(tallowoyloxyethyl) (2-hydroxyethyl) methyl ammonium methylsulfate, or of the type of water-soluble mono- and polyquats comprising one or more alkyl or alkenyl groups attached to the nitrogen either directly or by means of a functional group like oxyalkylene, polyoxyalkylene, and preferably a cleavable group like an ester or amide function. It is noted that the term water-dispersible compounds is meant to denote compounds that have a solubility in water of about 0.1%w/w or less at room temperature, while the term water-soluble compounds is used to refer to compounds with a solubility in water of greater than about 1%w/w at room temperature. Preferred are cationic surfactants that are water-soluble, of which typical examples include:
monoalkyl quats like cocotrimethyl ammonium chloride, hexadecyl trimethyl ammonium bromide, hexadecyl trimethyl ammonium chloride, octadecyl trimethyl ammonium chloride, tallow trimethyl ammonium chloride, and tallow (hydroxyethyl) dimethyl ammonium chloride;
monoester quats like Me3xe2x80x94N+xe2x80x94CH2CH2OC(O)R Xxe2x88x92, Me3xe2x80x94N+xe2x80x94CH2C(O)OR Xxe2x88x92, Me2xe2x80x94N+xe2x80x94(CH2CH2OH)CH2CH2OC(O)R Xxe2x88x92, Me2xe2x80x94N+xe2x80x94(CH2C(O)OMe)CH2CH2O(O)CR Xxe2x88x92, wherein R=C8-22 fatty acid based and X=Cl, Br, MeSO4, or acetate;
amidoquats like RCONHCH2CH2CH2N+xe2x80x94Me3 Xxe2x88x92;
water-soluble polyolester quats as described in EP-A-0 638 639, and
water-soluble polyquats comprising at least one C8-22 moiety with a preferred N/C8-22 moiety ratio of 1:2 to 2:1.
More preferred water-soluble or self-emulsifying cationics contain C16-18 groups. Most preferred are the C16-18 monoalkyl and monoester quats. It was especially remarkable that water-soluble quaternary ammonium compounds, which as such exhibit just a minor or medium softening performance, have such a softening performance boosting effect.
Hydrophobic nonionics that can be used as performance boosters according to the invention include, but are not limited to, fatty alcohols like stearic alcohol, cetearyl alcohols or (hydrogenated) tallow alcohols, fatty acids like stearic acid or (hydrogenated) tallow fatty acids, and mono-, di- and/or triglycerides like coconut, palm, palm kernel, soya, oleic, tallow, rapeseed, canola, behenic and eruca oils, which optionally may be at least partly hydrogenated. C16-18 alkyl groups-containing alcohols like hydrogenated tallow alcohol, hydrogenated tallow fatty acid, glycerol monostearate, and glycerol distearate are especially preferred. Other useful hydrophobic nonionics include alkoxylated, preferably ethoxylated, derivatives like C8-22 fatty alcohol alkoxylates, C8-22 fatty acid alkoxylates, C8-22 fatty amide alkoxylates, alkoxylated C8-22 glycerides, and mixtures thereof. Such hydrophobic nonionics typically have a HLB value of below 8, preferably below 5, in order to be effective.
The performance booster may be applied alone or in any combination with other known performance boosters. The weight ratio in which the (combination of) alkoxylated sugar esters and the (combination of) performance boosters are used typically ranges from 95:5 to 40:60%w/w. Preferably, the ratio between alkoxylated sugar esters and performance boosters ranges from 85:15 to 50:50 %w/w. If a combination of water-dispersible quats and hydrophobic non-ionic performance boosters is used according to the invention, then the preferred ratio of quat to nonionic is from 70:30 to 90:10%w/w. For combinations of water-soluble type of quats and hydrophobic non-ionic performance boosters the preferred ratio is from 0.1:99.9 to 50:50%w/w.
Even more preferred are combinations of alkoxylated sugar esters prepared by transesterification of glycerides, and still containing the residual mixture of non-ionic mono-, di-, and tri-glycerides, with one or more water-soluble cationic performance boosters. Preferably, such mixtures comprise 40-60%w/w of alkoxylated sugar ester, 40-60%w/w mono-, di- and/or tri-glycerides, and 40-60%w/w of water-soluble cationics, up to a total of 100%.
It is noted that the melting point of the alkoxylated sugar ester may have an influence on its performance as a softening agent. This feature was not optimised in the following examples. However, the skilled person will have no difficulty in varying, for example, the chain length of the fatty acid moiety of the alkoxylated sugar ester, the degree of alkoxylation, the types and ratio of epoxides used to alkoxylate the sugar (ester) or the type of sugar that is used as a starting material, in order to obtain products with optimum performance.
The compositions according to the invention can also contain one or more optional ingredients that do not impart the softening performance. Examples of optional ingredients that can be used are perfumes, perfume carriers, electrolytes, pH buffering agents, fluorescers, colourants, antifoaming agents, antiredeposition agents, anti-shrinking agents, anti-wrinkle agents, anti-spotting agents, anti-oxidants, anti-corrosion agents, antistatic agents, thickeners, enzymes, optical brighteners, opacifiers, germicides, fungicides, drape imparting agents, sunscreens, colour care agents, and ironing aids.
Other than for use in fabric softening, the alkoxylated sugar esters can also be used for conventional surface treatments. The alkoxylated sugar esters are, for instance, very suitable for use in personal care applications, such as hair and skin conditioners. For example, the use of the alkoxylated sugar esters according to the invention, especially in combination with water-soluble quaternary ammonium compounds, in hair rinsing compositions led to an efficient reduction of combing force and fly-away. The non-ionic nature of the alkoxylated sugar esters allows easy formulation of conditioning shampoos comprising them. Furthermore, the low impact on the environment (low ecotoxicitity) and resistance to long-term crystallisation make the alkoxylated sugar esters according to the invention particularly suitable for use in car-rinse applications. Finally, it is expected that the alkoxylated sugar esters according to the invention can be used with advantage in fluff and tissue softening, conveyor belt lubricants, mineral flotation, and manufacturing processes of organoclays.
The invention is further elucidated by the examples given below.
The HLB value as given for the various compounds throughout this document is determined according to a practical test derived from the methods as published in xe2x80x9cThe HLB system, a time saving guide to emulsifier selectionxe2x80x9d by ICI Americas Inc, revised March 1980. Use is made of the principle as described therein that the HLB value of a mixture of emulsifiers is the weight averaged HLB value of each emulsifier. More particularly, Pioneer(copyright) 2076 paraffinic oil ex Hansen and Rosenthal is known to have a required HLB value of the emulsifier system of 10 in order to obtain the most stable oil in water (O/W) dispersion in demineralised water. In order to determine the HLB value of a test material with a HLB value below 10, it is combined with a known emulsifier with a HLB value greater than 10, in our case a polyoxyethylene-20 sorbitan monolaurate with HLB value 16.5 (supplied as Armotan(copyright) PML20 ex Akzo Nobel), in specific weight ratios. By determining which combination gives the best O/W dispersion, one can calculate the HLB value of the test material on the basis of the weight ratio. If so desired, subsequent further tests with more narrow mixing ratios can be performed. From these test the HLB value of the test material can be determined with an accuracy of about 0.25.
The dispersion stability of the softening compositions according to the invention is measured by dispersing a total amount of 5 grams of the (combination of) alkoxylated sugar esters and optional performance booster(s) in 95 grams of water, and transferring the dispersion to a graduated cylinder of 100 ml. After 1 and 24 hours the degree of phase separation is measured. The dispersion stability is expressed in terms of volume percentage of dispersed (W/O) phase.
The softening compositions according to the invention were evaluated for their softening performance in a fabric softening panel test. Pre-washed terry towels (using phosphate-free test detergent IEC-456, type A, from WFK-Institutes, Krefeld, Germany) were treated with the test material at a use level of typically 1.25 g per kg of fabric. The treated towels were line dried for 20 hours at 20xc2x0 C. and 50% relative humidity, and cut into strips of 10 by 20 cm. A test panel of 24 people evaluated the softness in comparison with three standards (see below), and the data was statistically processed in accordance with standard DIN 10954.
References were selected as follows:
1) dimethyl-di(hydrogenated tallow) ammonium chloride (Arquad(copyright) 2HT ex Akzo Nobel), a conventional water-dispersible (fabric) softener,
2) 1 -methyl-2-tallowalkyl-3-tallowamido-ethyl imidazolinium methosulfate (Rewoquat(copyright) 7500 ex Witco), a conventional water-dispersible softener, and
3) untreated (no fabric softener used).
The performance of the tested fabric softener was ranked as follows:
+++ if equal to or better than Arquad 2HT
++(+) if significantly better than Rewoquat 7500
++ if equal to or better than Rewoquat 7500
+(+) if significantly better than untreated
+ if equal to or better than untreated
xe2x88x92 if worse than untreated
Significant meaning with a probability of at least 95% according to DIN 10954.

Use of alkoxylated sugar esters in liquid aqueous softening compositions


A nail lacquer for the treatment or prevention of fungal infections, such as, onychomycosis, includes fungicidally effective amount of ciclopirox, econazole, or other antifungal agent in a compatible film-forming lacquer vehicle which includes a water-insoluble film-forming polymer; pentadecalactone, or similar cyclic lactone compound or derivative thereof, and volatile solvent. The pentadecalactone functions as a plasticizer for the film-forming polymer and as a penetration enhancer for the antifungal agent. The composition, when applied to the nails provides a hard, clear, water-resistant film containing the antifungal agent. The compositions are used for the treatment of onychomycosis.

(1). Field of Invention
This invention relates to antifungal nail lacquer compositions useful in the treatment of onychomycoses or other fungal infestations affecting toe nails or finger nails using the nail lacquer composition. More particularly, the invention relates to antifungal nail lacquers which may be applied to nails to form films from which the antifungal agent will be released and become available for nail penetration; and to the method for treating or preventing fungal infestations of animal nails by applying the antifungal composition to the infected nail or to the fungal susceptible nail.
(2). State of the Prior Art
Fungal infection of the nails, commonly referred to as onychomycosis, is most frequently caused by dermatophytes but also can be caused by molds and Candida. Mixed infections also occur. Onychomycosis includes dermatophyte infection of the nail plate and includes infection of nails by any fungus, ineluding yeast or molds. Thus, for example, onychomycosis serves as a reservoir for dermatophytes and contributes to treatment failure and recurrence of tinea pedis.
Most common causes of tinea unguium are Trichophyton rubrum (most frequent), T. mentagrophytes, and Epidermophyton floccusum. Onychomycosis due to nondermatophytes is usually caused by Candida species.
Nail lacquers for the treatment of onychomycoses and similar fungal infections affecting nails (toe nails and/or finger nails) of humans, in particular, or other animals, are known. Representative examples are described in the patent literature, of which the following U.S. Pat. Nos. can be mentioned:
4,957,730 (1-hydroxy-2-pyridone in water-insoluble film-former);
5,120,530 (amorolfine in quaternary ammonium acrylic copolymer);
5,264,206 (tioconazole, econazole, oxiconazole, miconazole, tolnaftate, naftifine hydrochloride, in water-insoluble film-former); 5,346,692 (with urea and dibutyl phthalate plasticizer);
5,487,776 (griseofulvin as colloidal suspension).
Other U.S. Pat. Nos. which relate to antifungal products include, for example, 4,636,520, 5,002,938, 5,110,809, 5,219,877, 5,391,367, 5,464,610, 5,696,105.
Effectiveness of nail lacquers as a delivery vehicle for topically administering the antifungal agent amorolfine is described by Jean-Paul L. Marty, J. of the European Academy of Dermatology and Venereology, 4(Suppl. 1), pp.S17-S21 (1995). As described by the author, the film-generating solution as the lacquer base for the active principle basically consists of volatile solvent (ethanol, ethyl/butyl/methyl acetate, methylene chloride, methyl ethyl ketone, isopropanol), and a non-water-soluble polymer (methacrylic acid copolymers, vinyl polymers) which leaves a thin continuous film following evaporation of the solvent. Plasticizers (triacetin, dibutyl phthalate) impart sufficient mechanical flexibility to prevent flaking and removal.
More recently, some of the present inventors developed highly effective antifungal nail lacquer formulations which incorporated 2-n-nonyl-1,3-dioxolane or related dioxolane, dioxane and acetal compounds as skin (nail) permeation enhancers (SPE) and also, surprisingly, discovered that the SPE compounds function as plasticizers for the film-forming polymer. Thus, the nail lacquer formulation containing the dioxolane, dioxane and acetal classes of skin penetration enhancing compounds were able to be formulated without additional plasticizer while still providing clear, hard, water-resistant films exhibiting good adherence to nails and from which the antifungal agent could be readily dispensed into the affected nail. These antifungal nail compositions are disclosed in WO 99/39680, published Aug. 12, 1999.
Based on this experience, the present inventors attempted to find other penetration enhancing compounds which would also be useful in formulating antifungal lacquer compositions and capable of functioning as plasticizer for the film forming polymers of lacquer formulations. As a result, it was discovered that the skin penetration enhancing cyclic lactones and derivatives thereof, as disclosed in U.S. Pat. Nos. 5,023,252 and 5,731,303, the disclosures of which, are incorporated herein, in their entireties, also are compatible with a range of lacquer formulations containing film-forming polymer, antifungal agent and solvent. The present invention is based on this discovery.
The present invention provides an antifungal nail lacquer composition which will provide clear, hard, films adherent to nail surfaces.
According to the present invention there is provided a nail lacquer formulation incorporating an antifungal agent, which formulation, when applied to nails may yield a substantially clear film, for use in the treatment or prevention of fungal infestations or infections on or associated with nails.
In particular, the present invention provides a composition effective for the treatment or prevention of fungal infections of nails, comprising:
(a) at least one antifungal agent effective in the treatment or prevention of onychomycoses;
(b) a plasticizing and penetration enhancing agent selected from compounds of the following formula (I):
xe2x80x83wherein
A is is group having the structure
m and n are integers having a value from 1 to 20 and the sum of m+n is not greater than 25,
p is an integer having a value of 0 or 1,
q is an integer having a value of 0 or 1,
r is an integer having a value of 0 or 1,
R represents hydrogen or a straight or branched chain alkyl group having from 1 to 6 carbon atoms, and,
R1, R2, R3, R4, R5 and R6, each, independently, represent hydrogen or a straight or branched chain alkyl group having from 1 to 6 carbon atoms, with the provisos that
(i) only one of R1 to R6 may be said alkyl group, and
(ii) when p, q and r have a value of 0, m+n is at least 11,
(c) water-insoluble, film-forming polymer; and,
(d) volatile solvent.
The composition, when applied to nails, forms, upon evaporation of the volatile solvent, a film lacquer from which the antifungal agent is releasable and becomes available to treat or prevent fungal infection.
The invention also provides lacquer compositions effective for providing long-lasting, water-resistant adherent films on animal (e.g., human) skin and nails comprising a substantially non-aqueous solution of water-resistant, film-forming polymer, and plasticizing effective amount of at least one compound of formula (I).
The resulting water-resistant, adherent films will be suitable as a delivery matrix for drugs, including antifungal agents and others. When such film with drug incorporated therein, is deposited on animal, especially human or other mammal, skin or nail, the drug can leach from the film and be capable of being absorbed by or transported into and through the skin or nail.
The present invention provides antifungal nail lacquer compositions capable of forming films which will adhere to nails upon evaporation of the volatile solvent from the film-generating solution of nail lacquer composition. These films allow diffusion of active principle(s) included in the lacquer composition from the resulting film.
The cyclic lactones and related compounds as disclosed in the aforementioned U.S. Pat. Nos. 5,023,252 and 5,731,303, are described only as enhancers for penetration of various pharmacologically active principles through the skin. The compounds of formula (I), additionally, will provide a plasticizing effect for film-forming polymers of lacquer compositions and, therefore, are sometimes referred to hereinafter as PSPE""s (xe2x80x9cplasticizing skin penetration enhancersxe2x80x9d).
The preferred PSPE""s for use in the present invention are the cyclic lactones of formula (I):
wherein
A is is group having the structure
m and n are integers having a value from 1 to 20 and the sum of m+n is not greater than 25,
p is an integer having a value of 0 or 1,
q is an integer having a value of 0 or 1,
r is an integer having a value of 0 or 1,
R represents hydrogen or a straight or branched chain alkyl group having from 1 to 6 carbon atoms, and,
R1, R2, R3, R4, R5 and R6, each, independently, represent hydrogen or a straight or branched chain alkyl group having from 1 to 6 carbon atoms, with the provisos that
(i) only one of R1 to R6 may be said alkyl group, and
(ii) when p, q and r have a value of 0, m+n is at least 11.
Examples of the alkyl group for R and R1 to R6 include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, amyl, hexyl, and the like.
Preferably, each of R1 and R1 to R6 are hydrogen atoms. These preferred compounds of formula (I) are, therefore, cyclic lactones.
Another preferred class of compounds of formula (I) may be represented by the following general formula (I-A):
wherein X, Y, R, A, m, n, p, q and r, are as defined above.
Preferably, in formula (I-A), R is hydrogen.
The amount of enhancer compound is selected to provide the desired plasticization of the film-forming polymer and the desired delivery rate for the active compound but, taking into consideration such additional factors as, product stability, side effects, carrier system and the like. Generally, depending on the particular antifungal agent and film-forming polymer, amounts of the PSPE compound in the range of from about 0.5 to 35%, preferably from about 2 or 3 up to about 25 or 30 percent, especially from about 5 to 20 or 25 percent, most especially, from about 8 to 20% by weight of the total composition, will be compatible with the other ingredients of the lacquer composition and should provide transungal delivery of the active principle over the duration of the film on the nail. Within these ranges, the desird results (flexibility, release and skin permeation characteristics) may usually be achieved without incorporating additional co-solvents or plasticizers.
The PSPE""s are, generally speaking, compatible with acrylate and methacrylate copolymers. Compatibility between the film-forming polymer and the PSPE compounds may be readily determined by one of ordinary skill in the art, such as, for example, by formation of a single homogenous phase when the polymer and PSPE are mixed together, and, more particularly, by formation of a clear film upon evaporation of solvent. As will be appreciated by those skilled in the art, various factors, such as, for example, polarity of xe2x80x9cmerxe2x80x9d units of the polymer, molecular weight, and the like, will be considered for compatibility.
It is expected that the plasticizing and adhesion promoting functions of the subject PSPE compounds may also be exhibited with the below-described film-forming polymers, for virtually any drug which may be dissolved in the polymer/enhancer compound matrix, with or without the assistance of solvents or co-solvents. Thus, drugs which may be topically administered to the skin as well as drugs which are adapted for use in treating nails for onychomycoses or other ailments, may be incorporated into the nail and skin-adherent polymer plus enhancer compound film-forming composition of this invention.
The film-forming polymers which may be used in the present invention are not particularly limited and may be chosen from among any of the film-forming polymers previously used in or useful for nail lacquer film-forming polymers and which are compatible with the PSPE and which have good adhesion to nail keratin (and/or skin) and form water-insoluble and/or water-resistant films which permit release of the antifungal agent and also the steroidal antiinflammatory agent, if present.
Examples of water-insoluble, film-forming polymers which may be used in the nail lacquer compositions of this invention, include, for example, polyvinyl acetate, mixed polymers (or copolymers) of vinyl acetate with acrylic or methacrylic acid, copolymers of (meth)acrylic acid and (meth)acrylate esters, copolymers of (meth)acrylic acid esters with amino group and/or quaternary ammonium group-containing comonomers, and the like. These polymers may be used alone or in mixtures with each other or with other film-forming polymers that will not impair the objectives of this invention.
As used in this application, the term xe2x80x9clowerxe2x80x9d in connection with xe2x80x9calkylxe2x80x9d, etc., refers generally to carbon chain lengths of up to 6 carbon atoms, however, the preferred lower alkyl groups typically have from 1 to 4 carbon atoms.
Especially preferred film-forming polymers include acrylate (co)polymers, methacrylate (co)polymers, and copolymers of alkyl vinyl ether and maleic anhydride. For example, a preferred acrylic copolymer comprises recurring units of at least one of the following moieties (IV) and (V):
wherein R1 represents H or CH3; and R2 represents an alkyl group of from 1 to about 12 carbon atoms, preferably from about 2 to about 12 carbon atoms, especially preferably, from about 4 to about 10 carbon atoms. The alkyl group may be linear or branched. Examples of alkyl groups for R2 include methyl, ethyl, propyl, isopropyl, t-butyl, isobutyl, n-butyl, n-pentyl, 4-methyl-n-pentyl, n-hexyl, n-heptyl, n-octyl, 2-methyloctyl, n-nonyl, n-decyl, n-dodecyl, and the like.
Another useful acrylic copolymer comprises recurring units of a moiety of formula (VI)
wherein R3 represents an alkyl group, such as, for example, the alkyl groups described above for R2; preferably an alkyl group of at least two and up to about 12 carbon atoms, especially preferably C4 to C10 alkyl.
Acrylic copolymers which comprise recurring units of formula (V) or formula (VI) or both formulas (V) and (VI), and, optionally, recurring units of formula (IV), as defined above, wherein at least one of R2 and R3 represents an alkyl group having at least 4 carbon atoms, are particularly preferred.
Another preferred class of acrylic copolymer comprises recurring units of acrylic and/or methacrylic acid esters and recurring units of a moiety containing a cationic amine and/or quaternary ammonium group, such as, for example, carboethoxy-t-butyl ammonium.
As is well known in the art, the cationic amine group may be quaternized by reaction of the amine with an alkylating agent or other appropriate reagent to form a salt.
For example, any of the water-insoluble quaternary ammonium group containing acrylic copolymers disclosed in the aforementioned U.S. Pat. No. 5,120,530, the disclosure of which is incorporated herein by reference thereto, may be used as the film-forming copolymer in the compositions of the present invention.
Another preferred example of the water-insoluble, film-forming polymer comprises a copolymer of alkyl vinyl ether, such as, for example, methyl vinyl ether or ethyl vinyl ether, and at least one comonomer of a monoester of a dicarboxylic acid. Examples of such comonomer of a monoester of a dicarboxylic acid are shown by the following formula (VII):
wherein R4 represents a lower alkyl group, especially an alkyl group of from 1 to 4 carbon atoms, such as, for example, methyl, ethyl, propyl.
See also the film-forming polymers disclosed in the aforementioned U.S. Pat. No., 5,264,206, and the other patents mentioned above, which may also be used in this invention.
Film-forming polymers useful in the present invention are commercially available, such as, for example, the acrylic copolymers sold by National Starch Co. under the tradename DERMACRYL, e.g., DERMACRYL 79, DERMACRYL LT; the amine or quaternary ammonium group containing acrylic copolymers sold by Rohm (a division of Huls Group) under the tradename EUDRAGIT, it e.g., EUDRAGITs E, RS, RL,; the methylvinyl ether copolymers sold by ISP Corp. under the tradename GANTREZ, e.g., GANTREZ ES-3351, GANTREZ ES-425, ES-435; the quaternary ammonium acrylic copolymers sold by National Starch Co. under the tradename AMPHOMER, e.g., AMPHOMER LV-71. Particularly good results have been obtained with each of the following commercially available products:
The amount of film-forming polymer will depend on such factors as, for example, the molecular weight of the polymer, the desired thickness of the resulting film, the degree of water-resistance and the intended duration and delivery rate of the active agent(s), the compatibility with the other ingredients, and the like. Usually, however, satisfactory results are obtained when the amount of film-forming polymer is in the range of from about 10 to about 70 percent, preferably from about 15 to about 50 percent, especially from about 20 to 40 percent by weight of the total nail lacquer composition.
In terms of weight ratio between film-forming polymer and penetration enhancing and plasticizing compound of formula (I), suitable values of polymer:enhancer/plasticizer generally-range from about 4:1 to about 1:1, preferably from about 3:1 to about 1.2:1, especially preferably from about 2:1 to about 1.2:1. The plasticizing function of the compounds of formula (I) is exhibited over generally the same or somewhat higher concentrations as the skin penetration enhancing function. Therefore, when other plasticizing additives, as described below, are included in the compositions of this invention, the ratio of polymer to enhancer may be somewhat higher than the above ranges, for example, from about 5:1 to about 1:1.
Conventional plasticizers compatible (e.g., forming a homogenous solution and clear films) with film-forming polymers may be included in the compositions of this invention to provide additional flexibility to the dried polymer film upon evaporation of the solvent, and/or additional releasability of the antifungal agent as well as for the PSPE compound. Suitable plasticizers include, for example, 1,2,3-propanetriol triacetate (triacetin), dibutyl phthalate, dioctyl phthalate, dibutoxy ethyl phthalate, diamyl phthalate, sucrose acetate isobutyrate, butyl acetyl ricinoleate, butyl stearate, triethyl citrate, dibutyl tartrate, polyethylene glycol, dipropylene glycol, polypropylene glycols, propylene glycol, glycol fatty acid esters, such as, propylene glycol dipelargonate, and the like.
Particularly preferred plasticizers are glycols, such as propylene glycol and dipropylene glycol, glycol esters, phthalate esters, citrate esters, polyethylene glycols, and polypropylene glycols.
The type and amount of additional plasticizer, when present in the formulation, affects resistance of the dried polymer film to water and may also affect the release rate of the active drug ingredients as well as that of the PSPE compound. Those skilled in the art will recognize that the degree of water resistance can also be controlled by the type and amount of the plasticizer(s), the nature of the active principles, the choice of polymer (e.g., amount of acid groups in the polymer, etc.), the amount of the polymer, and the like.
When additional plasticizer is present it will generally be used in amounts which depend on the types and amounts of the film-forming polymer and the PSPE, most usually in the range of from about 0.5 to about 20 percent, preferably from about 2 to 10 percent, especially, from about 4 to 8 percent, based on the total weight of the composition.
While additional plasticizers may be incorporated in the invention compositions, as noted above, sufficient flexibility and adhesion, as well as compatibility (both wet and dry) between the respective ingredients, will usually be achieved without the addition of conventional plasticizers.
Solvents which may be used in the nail lacquer compositions of this invention are also not particularly critical but may be selected from among the usual physiologically safe organic solvents for lacquer compositions, so long as the active principles and film-forming polymers are soluble therein and so long as the lacquer is easy to apply and sufficiently volatile to provide acceptable drying times, usually dry to the touch in less than about 5 minutes, preferably less than about 2 minutes. As examples of such solvents mention may be made of lower alkanols, e.g., ethanol, propanol, isopropanol, butanol, isobutanol; lower alkyl esters of lower carboxylic acids, e.g., ethyl acetate, propyl acetate, n-butyl acetate, n-amyl acetate; lower alkyl ethers, e.g., methyl ether, methyl ethyl ether; lower alkyl ketones, e.g., methyl ethyl ketone; halogenated hydrocarbons, e.g., methylene chloride, methyl chloroform; aromatic hydrocarbons, e.g., toluene; cyclic ethers, such as, tetrahydrofuran, 1,4-dioxane; and mixtures thereof. Anhydrous ethanol (EtOH) is especially preferred.
The solvents used in the nail lacquer formulations of this invention are generally and preferably non-aqueous. However, in some cases small amounts of water, generally less than about 10%, preferably less than about 5% by weight of total solvents, may be used if not substantially impairing the homogeneity, clarity and solubility of the various ingredients in the lacquer solution. For example, ethanol when used may sometimes be added in the form of a 95% ethanol solution.
Again, in view of the good compatibility between the film-forming polymer and the enhancer/plasticizer compounds of formula (I), use of co-solvents, such as propylene glycol, in addition to solvent, e.g., ethanol, are usually not required and, therefore, may be omitted.
On the other hand, however, it may be desirable and, in some cases, preferred, to decrease the water-resistance of the dried polymer film, for example, to facilitate removal of the film after release of all or most of the active ingredients. Thus, in addition to a lacquer film from which the active ingredients are released over periods of several days to about 1 week or longer, lacquer films from which the active ingredient is at least substantially released over shorter periods of time, such as one day, may be desirable since many individuals are accustomed to and prefer treatments requiring applications of a drug on a daily basis.
Techniques for increasing the availability of the active ingredients for transungual delivery have been described above. When the release rate of active ingredient becomes low the film may be removed by application of suitable solvents, such as those described above, e.g., alcohols, acetone, ketones, etc., and/or by scraping or brushing, as also well known in the nail lacquer art.
Often, mixtures of volatile solvents of different boiling points, usually a low boiling solvent in the range of from about 40xc2x0 C. to about 100xc2x0 C. with a medium boiling solvent (boiling point up to about 150xc2x0 C.) may be selected to provide drying times of no more than a few minutes or less, with uniform evaporation rates, good flow and viscosity characteristics and other desirable lacquer parameters, as well known in the cosmetic art. In some cases, high boiling point solvents, such as, for example, cellosolve, butylcellosolve acetate, butyl cellosolve, ethyl cellosolve, and the like, may be added in small amounts provided they do not impede the fast drying property and other desired characteristics.
In this connection, in its preferred embodiment, all of the volatile and non-volatile ingredients are compatible with each other and form upon mixing clear solutions which are stable against phase separation over a wide temperature range above and below room temperature, such as, for example, from temperatures within the range of from about xe2x88x9210xc2x0 C. to about +135xc2x0 C.
Another important characteristic of commmercially acceptable products is that the films formed upon evaporation of the solvent(s) and any other volatile components are strongly adherent to the nail and are water-resistant, namely, capable of withstanding repeated normal washing with soapy water for at least 1 day, usually up to about 5 or more days, preferably, at least one week, depending on the amount of antifungal agent in the film and upon the release rate of the active principles from the film. In addition, the dry films, for cosmetic appearance, should be substantially clear and transparent.
It is also within the scope of the invention to include colorants, such as pigments and/or dyestuffs, nacreous agents, pearlescent agents, fillers, and the like, to cover the nail, for example, to hide any unsightly manifestations of the fungal, yeast or other infection, or otherwise as may be cosmetically desirable.
Other conventional additives customarily present in cosmetic or medicinal nail lacquers may be included in the present formulations in their usual amounts so long as they do not interfere with the diffusion of the active principles and other parameters of the lacquer composition and dried polymer-film. Examples of such additives include, sedimentation retarders, chelating agents, antioxidants, silicates, aroma substances, wetting agents, lanolin derivatives, light stabilizers, antibacterial substances, and the like.
The lacquer compositions of this invention, with or without antifungal agent, may be prepared following any of the procedures normally employed in the nail lacquer field, noting that most of the ingredients are added as mobile liquids such that normal mixing techniques are available, with no particular order of addition of the respective ingredients being required. Generally, however, the polymer film-former, if in powder form, should be added gradually to some or all of the liquid components in such manner as to avoid clumping and resulting protracted dissolution times. Other ingredients may be added as convenient, as will be readily apparent to the practitioner.
The antifungal agent films obtained from the nail lacquers of this invention should be effective in treating onychomycoses and other fungal infections. Usually, repeated applications of the antifungal lacquer will be made over a period of several weeks to several months, depending on the severity of the infection, the amount of active agent, and the condition of the nails of the patient. The antifungal agent containing film will contain sufficient active principle to be diffused through the nail over a period of at least 1 day, and up to about 7 days. Since the film will remain in place usually for the entire period of diffusion, applications of the antifungal nail lacquer need be repeated only about once per day to about once per week. For example, it may be desired to provide formulations for daily application during the initial period of usage until the patient observes substantial reduction in the degree and extent of infection and thereafter to provide different formulations designed for less frequent applications, such as every other day, weekly, etc.
In addition to treating an existing infection or fungal infestation, the nail lacquers of this invention may also be applied prophylactically to the nails of a healthy individual who is or who believes he or she may be at risk for a mycotic infection, as a result, for example, of occupation, geographical location or otherwise. The manner of use is otherwise identical to the use in treating an existing infection, however, smaller dosages, but still at least above the MIC of the antifungal agent, may be sufficient in many cases to prevent the onset of fungal infection in the event of fungal contamination or infestation.
There is no particular limitation on the antifungal agents used in the compositions of this invention; any of the agents known to be effective for this purpose may be used and a listing of such compounds may be found, for example, in any current edition of The Merck Index under the headings xe2x80x9cAntifungal (Antibiotic)xe2x80x9d and xe2x80x9cAntifungal (Synthetic)xe2x80x9d in the Therapeutic Category and Biological Activity Index section.
As examples of suitable antifungal agents mention may be made of, for example, polyenes, e.g., Natamycin, Nystatin; allylamines, e.g., Naftifine, Terbinafine; imidazoles, e.g., Bifonazole, Chlotrimazole, Econazole, Fenticonazole, Ketocanazole, Miconazole, Oxiconazole; triazoles, e.g., Fluconazole, Itraconazole, Terconazole; tolnaftate, ciclopirox, undecylenic acid, sulbentine, and morpholines, e.g., amorolfine, and the related morpholines disclosed in the aforementioned U.S. Pat. No. 5,120,530. The 1-hydroxy-2-pyridone compounds disclosed in U.S. Pat. No. 4,957,730, the disclosure of which is incorporated herein, by reference thereto, may also be used, as may the antifungal agents disclosed in any of the other patent documents discussed in the Background of the Invention.
In the present invention, the antifungal agents are, preferably, present in the free form, e.g., as acid or base, rather than in the form of their salts. In this regard, the free form of antifungal agent will usually have a higher diffusion rate through the nail than a salt of the same agent; or, the salt form of a drug may impair the water-resistance of the lacquer film.
The amount of the active antifungal agent or mixture of such agents in the composition will depend on such factors as its structure and antimicrobial activity, release rate from the polymer film, diffusion characteristics and penetration behavior in the nail. Generally, any amount effective to kill the infecting microorganism, which will generally be several to several tens to hundreds of times greater than the Mean Inhibitory Concentration (MIC), may be included in the nail lacquer (as applied) composition.
Typically, amounts of active antifungal agent in the range of from about 0.5 to 20 percent by weight, preferably from about 1 to 10 percent, by weight, of the total composition (including solvents, film-forming polymer, enhancer, etc.) will suffice for compositions for treatment as well as compositions for prevention. The amount of antifungal agent in the dried film will, therefore, depend on the amount of agent in the lacquer solution and by the thickness of the applied film. The thickness of the film can be controlled by, for example, controlling the viscosity of the lacquer solution, such as by the type and amount of polymer, types and amounts of solvents, etc.
Conversely, on the basis of the non-volatile components of the composition, the amount of active agent is generally about 1 to 50%, preferably about 2 to 35%, more preferably, from about 2 to 30%, especially preferably from about 5 to 20%, by weight of the composition (film-forming polymer(s), active(s), PSPE, additional plasticizer(s) and other non-volatile additives).
The antifungal nail lacquers according to this invention, by virtue of the incorporation of the penetration enhancer-plasticizer, as described above, may provide therapeutically effective concentrations of antifungal agent deep into the nail bed. The minimum value of the therapeutically effective amount of antifungal agent will depend on several factors, primarily the particular antifungal agent and the degree and severity and cause of onychomycoses or other fungal infection.
Generally concentrations of antifungal agent greater than at least about 150 ppm in deep nail bed should be reached to attain favorable clinical results.

Antifungal nail lacquer and method using same