Patent Description:
<NUM>,<NUM>-octanediol, with octane-<NUM>,<NUM>-diol, <NUM>,<NUM>-dihydroxyoctane and caprylyl glycol as well-known alternative names, is a well-known ingredient that is commonly used in personal care products and that offers a multitude of beneficial effects. Its hydrophilic diol-moiety enables the absorption of moisture from the atmosphere. The lipophilic alkyl-function provides further conditioning and emollient effects and helps the skin to retain its moisture. <NUM>,<NUM>-octanediol is also known for its broad spectrum antimicrobial activity, in particular against bacteria. This effect is observed already at low use-levels of between <NUM> wt. -% and <NUM> wt. The underlying mechanism of action is related to a physical weakening of cell membranes. Synergistic effects in conjunction with other antimicrobial agents are frequently observed.

Besides its wide application in hygiene and personal care products, <NUM>,<NUM>-octanediol can also be used as a valuable and cost-effective additive in a multitude of further, preferably aqueous formulations. Its weak surface activity suggests a variety of technical applications, such as rheology modification, solubilization of lipophilic components and enhancement of visual clarity.

Pure <NUM>,<NUM>-octanediol of more than <NUM> wt. -% content is a waxy solid at ambient temperature with a melting range of <NUM>-<NUM>. The substance frequently forms an undercooled melt that remains stable as a liquid below its melting point for an unpredictable period of time. Therefore, <NUM>,<NUM> octanediol is typically molten before its use by heating to temperatures ranging from <NUM> to about <NUM>. This mandatory melting process correlates with a variety of drawbacks:.

In summary, pure <NUM>,<NUM>-octanediol is inconvenient and expensive to use. Its handling as a hot melt can be harmful and is especially cumbersome in cold-process applications such as the production of toiletries, wet wipes or perfumes.

There are different solutions available in the state of the art which aim at overcoming the described drawbacks related to the handling of pure <NUM>,<NUM>-octanediol:.

None of the above-mentioned solutions provides a liquid form of <NUM>,<NUM>-octanediol without significantly altering its performance profile. Furthermore, none of the above-mentioned solutions contains a high concentration of <NUM>,<NUM> octanediol and at the same time does not separate upon repeated freezing and thawing.

<CIT> discloses stabilized multiple emulsions comprising the compounds a), b) and c), methods for the stabilization of multiple emulsions and the use of multiple emulsions as skin protection products, in particular for protection against aqueous noxa, where: a) at least one aliphatic unbranched diol with <NUM> to <NUM> carbon atoms in the hydrocarbon chain, b) at least one further branched or unbranched aliphatic diol with <NUM> to <NUM> carbon atoms in the hydrocarbon chain that is different from a), whereby the hydrocarbon chain may be interrupted by an oxygen atom, c) at least one single-value aliphatic alcohol with <NUM> to <NUM> carbon atoms in the hydrocarbon chain. <CIT> shows the problem that in embodiments of the multiple emulsions, <NUM>,<NUM>-octanediol is only used in rather low concentrations, and this in combination with similar or even higher concentrations of other water-soluble alkanediols, which is expected to significantly alter the performance profile of <NUM>,<NUM>-octanediol.

The composition disclosed in <CIT> comprises glyceryl caprylate and phenylpropanol in addition to caprylyl glycol, glycerin and water. However, caprylyl caprylate has limited stability and solubility in aqueous compositions and it is noted that phenylpropanol has a distinct odor, which restricts its use in compositions with no or different scents, such as odorless cosmetics.

<CIT> discloses blends of caprylohydroxamic acid, caprylyl glycol and one or more glycols or vicinal diols that are liquid at room temperature, such that the entire blend is liquid and therefore easy to blend into a cosmetic, toiletry or pharmaceutical emulsion.

The present invention relates to a hygiene product or pharmaceutical composition in the form of a gel or dressing, for topical application to the skin or mucosa including glycerol, at least one poly(meth)acrylate polymer, at least one polyethylene glycol with a molecular weight of less than <NUM>/mol, octanediol and water.

The present invention aims to resolve at least some of the problems and disadvantages mentioned above. In particular, it is desirable to solve the technical problem of providing a stable, liquid and easy to use form of <NUM>,<NUM>-octanediol by combining it with low-cost, safe and neutral additives for physical stabilization. The resulting blend should offer a safe and cost-effective alternative to pure <NUM>,<NUM>-octanediol while still providing maximum flexibility to a formulator.

In a first aspect, the present invention relates to a homogeneous liquid composition, according to claim <NUM>. Preferred embodiments of the homogeneous liquid composition according to the first aspect of the invention are shown in any of the claims <NUM> to <NUM>.

In a second aspect, the invention relates to a use of a homogeneous liquid composition according to the first aspect of the invention by dosing said composition as a liquid in batch and / or continuous processes where said composition is not heated above <NUM>, according to claim <NUM>. A preferred embodiment of the use according to the second aspect of the invention is shown in claim <NUM>.

In a third aspect, the invention relates to a use of a homogeneous liquid composition according to the first aspect of the invention in cosmetic, pharmaceutical, dermatological or hygienic preparations, according to claim <NUM>.

The expression "wt. -%", here and throughout the description unless otherwise defined, refers to the relative weight of the respective component based on the overall weight of the formulation.

The above-mentioned technical problem was solved by mixing <NUM>,<NUM>-octanediol with water and at least one additional C3-C4 alkanediol and/or C3-C4 alkanetriol. These mixtures were surprisingly found to stay liquid within a wide temperature range and not to separate after repeated freezing and thawing.

The phenomenon of freezing-point depression is well-known. It occurs essentially because the foreign molecules do not fit well into the crystal structure of the main component. In a simplified approximation, the freezing-point depression depends mainly on the number of dissolved particles and not on their structure. The freezing-point depression is therefore called a 'colligative property'.

The following equation, also known as Blagden's law, can be used to estimate the freezing-point depression of a liquid which occurs when other compounds are dissolved inside: <MAT>.

As can be seen from the above equation, the depression of the freezing point of a liquid is directly proportional to the number of foreign molecules per mass of the major component. However, the chemical structure of the additives can be disregarded only for diluted solutions. At higher concentrations the freezing point depression also depends on the structural properties and interactions of the different components.

Based on this common knowledge, additives consisting of small molecules or ions would have the biggest decreasing impact on the freezing point of a high-melting liquid. In view of applications in personal care products, water as well as short chain alkanediols or alkanetriols would be attractive candidates as additives for the purpose of freezing point depression. All these substances have a low molecular weight, are of low toxicity and of low odor, and they have a comparatively neutral behavior on skin and in formulations.

The partition coefficient between n-octanol and water, also called 'log POW' and performed according to OECD Test No. <NUM> at <NUM>, of <NUM>,<NUM>-octanediol is <NUM>. This value indicates that <NUM>,<NUM>-octanediol is a relatively lipophilic compound. In contrast to that, the log POW of short chain alkanediols and triols are negative and hence confirm their hydrophilic character. A specialist trained in the art could therefore expect that a mixture of water, <NUM>,<NUM>-octanediol and hydrophilic short chain alkanediols and/or alkanetriols would form a hydrophilic phase containing water, and a separate lipophilic phase containing <NUM>,<NUM>-octanediol. However, it was surprisingly found that <NUM>,<NUM>-octanediol forms stable, homogeneous and low melting solutions in combination with water and alkanediols and/or alkanetriols.

The solubility of water in <NUM>,<NUM>-octanediol exceeds <NUM>% at <NUM>. However, mixtures of <NUM>,<NUM>-octanediol with water tend to form highly viscous gels at ambient temperature which are hard to handle.

Glycerol, with glycerine and <NUM>,<NUM>,<NUM>-trihydroxypropane as well-known alternative names, is a C3 alkanetriol. The solubility of glycerol in <NUM>,<NUM>-octanediol exceeds <NUM>%. However, mixtures of <NUM>,<NUM>-octanediol and glycerol tend to be highly viscous and might separate at low temperatures. Furthermore, the addition of high amounts of glycerol to skin care formulations may cause a sticky skin-feel.

The miscibility of <NUM>,<NUM>-octanediol with C3-C4 alkanediols is well-known. However, comparably large amounts of these diols are needed for lowering the melting point of <NUM>,<NUM>-octanediol below <NUM>. Furthermore, C3-C4 polyols are highly hydrophilic components with a log POW of ≤ <NUM>, as detailed in the following table (Table <NUM>).

A specialist trained in the art could therefore expect that the addition of water to a mixture of <NUM>,<NUM>-octanediol and the above-mentioned short chain alkanediols or alkanetriols would lead to a phase separation. However, it was now surprisingly found that the addition of water to these mixtures increases their physical stability in addition to decreasing their melting points. Comparably lower concentrations of the short-chain polyols are therefore needed in order to obtain low-melting compositions. The concentration of the active component <NUM>,<NUM>-octanediol in the resulting mixture can be increased due to the presence of water. The aqueous mixtures are also more cost-effective and provide a higher flexibility during formulation compared to anhydrous mixtures. The lower necessary amounts of C3-C4 alkanediol or alkanetriol solvents additionally result in lower unwanted sideeffects in formulations and on skin.

In a first aspect, the invention relates to a homogeneous liquid composition consisting of:.

supplemented with water as component (C) up to <NUM> wt.

In a preferred embodiment, the invention relates to a homogenous liquid composition consisting of :.

The term "homogenous" or "homogeneous" as used herein has the meaning of a single and clear liquid phase. That is to say the ratio of solute to solvent remains the same throughout the composition and any existing particles a second separate liquid phase are not visible with the naked eye.

-% are expressed with regard to the total weight of the homogeneous liquid composition according to the first aspect of the invention.

In a preferred embodiment, the invention provides a homogeneous liquid composition according to the first aspect of the invention, wherein the composition comprises from <NUM> wt. -% to <NUM> wt. -%, more preferably from <NUM> wt. -% to <NUM> wt. -%, and even more preferably from <NUM> wt. -% to <NUM> wt. -% of water.

In a preferred embodiment, the invention provides a homogeneous liquid composition according to the first aspect of the invention, wherein the component (B) is at least one C3-C4 alkanediol and/or C3-C4 alkanetriol with a log POW from - <NUM> to -<NUM>, which is measured according to OECD Test No. <NUM> at <NUM>.

In a preferred embodiment, the invention provides a homogeneous liquid composition according to the first aspect of the invention, wherein the component (B) is selected from the group consisting of glycerol, <NUM>,<NUM>-propanediol, <NUM>,<NUM>-propanediol, <NUM>-methyl-<NUM>,<NUM>-propanediol, <NUM>,<NUM>-butanediol, <NUM>,<NUM>-butanediol, <NUM>,<NUM>-butanediol and <NUM>,<NUM>-butanediol.

In a preferred embodiment, the invention provides a homogeneous liquid composition according to the first aspect of the invention, wherein the component (B) is selected from the group consisting of glycerol, <NUM>,<NUM>-propanediol and <NUM>,<NUM>-propanediol.

In a preferred embodiment, the invention provides a homogeneous liquid consisting of :.

The use of two components (B) and (C), preferably glycerol (B) and water (C) is necessary in order to obtain a stable liquid composition together with <NUM>,<NUM>-octanediol in the high amounts. In the case where either only glycerol or only water is combined with <NUM>,<NUM>-octanediol, the corresponding binary mixtures will not be stable liquids. This decisive fact is not explicitly taught by the prior art. Glycerol and water are particularly advantageous due to their low toxicity and high availability. Glycerol and water are both "hydrophilic", while <NUM>,<NUM>-octanediol is a "hydrophobic" waxy solid. Obtaining a homogeneous, stable liquid composition from the mixture thereof is surprising.

The homogeneous liquid composition according to the first aspect of the invention is stable also after repeated freeze-thaw cycles, hence avoiding the necessity for homogenization prior to use. One such cycle comprises cooling of the composition below its melting point and subsequent warming above its melting point.

The homogeneous liquid composition according to the first aspect of the invention is a stable homogeneous liquid at low temperature. In a preferred embodiment, the invention provides a homogeneous liquid composition according to the first aspect of the invention, wherein the composition has a melting point of at most <NUM>, more preferably at most <NUM>, more preferably of at most <NUM>, and even more preferably of at most <NUM>. The melting point is defined as the lowest temperature where the composition is a clear liquid. It is therefore possible to use the compositions without the necessity of heating by using special equipment. Simple storage at common ambient temperature, for example of between <NUM> and <NUM>, is sufficient to obtain a uniform liquid.

In a preferred embodiment, the invention provides a homogeneous liquid composition according to the first aspect of the invention, wherein the composition has a low dynamic viscosity at <NUM>, preferably of at most <NUM> mPa·s, and more preferably of at most <NUM> mPa·s, as measured with a rotary viscometer at <NUM>. The homogeneous aqueous compositions according to the first aspect of the invention typically have a lower viscosity than comparable anhydrous mixtures. The composition comprising water is therefore easier to handle than water-free compositions, thereby improving productivity.

The origin of the components (A) and (B) can vary. The components can be produced starting from various feedstock by means of various technologies such as, but not limited to, organic chemistry, extraction, fermentation or combinations thereof, resulting in a petrochemical and/or vegetal and/or biotechnological origin.

The preparation of a homogeneous liquid composition according to the first aspect of the invention is preferably carried out at a temperature where all its components are liquids. However, it is also possible to dissolve solid components in liquid components. Any heating of the components can either take place directly in a mixing equipment or separately outside. The temperature during mixing should be selected in a way that the mixture stays above its freezing point, in order to ensure the uniformity of the mixture. The order of addition of the separate components can be selected according to practicality and availability of production equipment.

In a further embodiment of the invention, the homogeneous liquid composition is added to an aqueous mixture. A temperature of addition can be chosen according to the process. The preferred temperature of addition is between <NUM> and <NUM>. The most preferred procedures include an addition of said composition to an aqueous mixture without any additional heating.

In a second aspect, the invention relates to a use of a homogeneous liquid composition according to the first aspect of the invention by dosing said composition as a liquid in batch and / or continuous processes where said composition is not heated above <NUM>. Preferably, said dosing is performed continuously.

In a third aspect, the invention relates to a use of a homogeneous liquid composition according to the first aspect of the invention in cosmetic, pharmaceutical, dermatological or hygienic preparations.

The homogeneous liquid composition according to the first aspect of the invention can be used as ingredient for personal care products, such as, but not limited to:.

The composition according to the first aspect of the invention can be added to final formulations of personal care products at any time during the production process. The addition preferably takes place towards the end of the formulation process of the personal care products, in order to ensure a high concentration of <NUM>,<NUM>-octanediol in the water phase of the formulation.

The melting-point of different compositions comprising <NUM>,<NUM>-octanediol was measured. The individual components were thoroughly mixed in a liquid state. The liquid mixtures were cooled to -<NUM> and subsequently thawed by warming to <NUM> in steps of <NUM>. The melting point was defined as the lowest temperature where all components of the mixture were present as liquids. In the table below (Table <NUM>), relative concentrations of the components are expressed in wt. -%, referring to the relative weights of the respective components based on the overall weight of the composition.

The compositions according to embodiments of the invention (Examples <NUM>-<NUM>) are all clear liquids with a low-melting point of not more than <NUM>. The amounts of polyol additives necessary to achieve a stable mixture are lower in the compositions according to embodiments of the invention (Examples <NUM>-<NUM>) than in the comparative compositions (Examples <NUM>-<NUM>). The impacts of the additives on formulations comprising <NUM>,<NUM>-octanediol are consequently lower for compositions according to embodiments of the invention than for the comparative compositions.

The stability of embodiments of the composition of the invention mentioned in Examples <NUM>-<NUM>, was evaluated in Examples <NUM>-<NUM> by repeated freezing to -<NUM> and thawing to +<NUM>. Samples of <NUM> each were subjected to three consecutive freeze-thaw-cycles. The uniformity of the mixtures was subsequently determined by measuring the refractive indices of the upper and lower layers at +<NUM>. Comparative Examples <NUM>-<NUM> were evaluated as stated below in Table <NUM> for comparative purposes.

All the compositions according to embodiments of the first aspect of the invention (Examples <NUM>-<NUM>) had a uniform composition also after repeated freezing and thawing. The observed physical stability confirms that the stabilizing effect of water and short chain polyol additives persists also after solidification and subsequent melting.

Dynamic viscosities of several compositions according to embodiments of the first aspect of the invention were measured at <NUM> by using a rotary viscometer with spindle R1 at rotation speeds of <NUM>-<NUM> rpm, which corresponds to Examples <NUM>, <NUM>, <NUM> and <NUM> shown below in Table <NUM>. Comparative Examples <NUM>, <NUM>, <NUM> and <NUM> were evaluated as stated below in Table <NUM> for comparative purposes.

All the aqueous mixtures shown in the above table have a significantly lower viscosity than the corresponding water-free mixtures. The blends containing water are therefore easier to handle and dose than comparable anhydrous mixtures.

A liquid composition according to Example <NUM> was used to preserve and disinfect natural hydrosols. Hydrosols are commonly also known as hydrolats or floral waters. These are aqueous distillates resulting from a steam distillation of aromatic plants. Several hydrosols were subjected to microbial challenge tests according to ISO <NUM>, in order to evaluate their level of protection against microbial contamination. Furthermore, the number of colony forming units per gram (cfu/g) inside the hydrosols was determined in accordance with the European Pharmacopoeia, 10th edition, section <NUM>. <NUM> (Total Aerobic Microbial Counts, TAMC and Total Yeast and Mould Counts, TYMC). Results are shown in Table <NUM>, in which also comparative Examples are shown which were performed for comparative purposes.

The obtained challenge test results demonstrate that the crude or raw hydrosols are insufficiently protected against microbial contamination. This finding confirms a risk for contamination by microbes during handling and storage. Furthermore, the TAMC and TYMC analyses reveal the potential presence of microbes inside the raw hydrosols. In contrast to that, the hydrosols comprising a composition according to embodiments of the first aspect of the invention are essentially free of microbes and well protected against external microbial infection.

The liquid form of the added composition according to Example <NUM> allows for the addition of <NUM>,<NUM>-octanediol at ambient temperature without any heating during the handling of the hydrosols. The cold process saves time and energy. It also helps to preserve the original composition of the hydrosols, which contain volatile natural aroma ingredients. These components could partly evaporate upon heating, resulting in an undesired change of the odor profile.

A liquid composition according to Example <NUM> was added to a cleaning formulation at <NUM>, said cleaning formulation corresponds to Example <NUM> and of which the composition is shown in Table <NUM> below.

The cleaning formulation according to Example <NUM> is a shampoo. While the unprotected formulation failed a microbial challenge test according to ISO <NUM>, the same product containing the composition according to Example <NUM> reached criteria A according to ISO <NUM>. The production of a shampoo is typically a cold process. Adding a composition according to this invention instead of pure <NUM>,<NUM>-octanediol avoids the necessity for heating of the ingredient <NUM>,<NUM>-octanediol (INCI: caprylyl glycol). The cold process is more reproducible and saves times and energy.

A liquid composition according to Example <NUM> was added to a shampoo, which shampoo corresponds to Example <NUM> and of which the composition is shown in Table <NUM> below.

The resulting shampoo, which is also a hydrogel, reached criteria A in a challenge test according to ISO <NUM>. No heating was required for the addition of phase C. This production process could be therefore also carried out in continuous production equipment.

A liquid composition according to Example <NUM> was added to water, resulting in a mist formulation corresponding to Example <NUM> and of which the composition is shown in Table <NUM> below.

A clear solution was obtained upon stirring at ambient temperature. No heating was needed for the introduction of <NUM>,<NUM>-octanediol into water.

A liquid composition according to Example <NUM> was added to an O/W emulsion, resulting in a cream corresponding to Example <NUM> and of which the composition is shown in Table <NUM> below.

Claim 1:
Homogeneous liquid composition, wherein the composition is a homogeneous liquid at <NUM>, consisting of:
- as component (A) from <NUM> wt.-% to <NUM> wt.-% of <NUM>,<NUM>-octanediol; and
- as component (B) from <NUM> wt.-% to <NUM> wt.-% of at least one C3-C4 alkanediol and/or C3-C4 alkanetriol,
supplemented with water as component (C) up to <NUM> wt.-%.