3-hydroxypropylesters as solubility enhancers for lipophilic ingredients

Abstract

The present invention pertains to the use of at least one of compounds of formula (I) as a solubilizer or a co-solubilizer of a lipophilic substance in a water based preparation.

Description

Applicant: Symrise AGSerial Number: New ApplicationSymrise AGMuhlenfeldstraBe 1 , 37603 Holzminden,Germany3-Hydroxypropylesters as solubility enhancers for lipophilic ingredientsThe present invention primarily relates to 3-Hydroxypropylesters and their use as a solubilizer or a co-solubilizer of a lipophilic substance in a water based preparation. It is one of a series of inventions related to 3-Hydroxypropylesters and structurally related compounds co-filed by the same applicant and on the same date as PCT patent applications, which are titled “3-Hydroxypropylesters as antioxidants and tocopherol boosters”, “3-Hydroxypropylesters as solubility enhancers for lipophilic ingredients”, “3- Hydroxypropylesters as foam and viscosity modulating agents in surfactant containing formulations”, “3-Hydroxypropylesters as emulsifying agents”, “3-Hydroxypropylesters as antimicrobial agents”, and “Antimicrobial synergies”, whose content is incorporated herein by way of reference.Personal care preparations including cosmetic and dermatological pharmaceutical preparations are water based, complex mixtures mainly intended to be applied topically. Many of them contain substances with significant lipophilic properties. In fact, a broad spectrum of lipophilic substances are used in a wide range of personal care preparations to serve a variety of functions, such as anti-inflammatory, anti-itching, anti-redness, antidandruff, anti-microbial, anti-perspirant, anti-cellulite, anti-viral, anti-oxidative, anti-wrinkle, skin-whitening, skin tanning, pain-reducing, swelling reduction, skin barrier strengthening, anti-mycotic, anti-sagging, deodorant and skin soothing properties.The drawback of the use of functional substances being lipophilic is their poor water solubility. This property makes it particular difficult to incorporate them in formulations mainly constituted of water including aqueous / alcoholic and aqueous / glycolic formulations, which often provides the basis for liquid soaps, shampoos and gels. With lipophilic substances it is also challenging to prepare clear and non-turbid formulations such as solutions for wet wipe, micellar water, mouth wash, after shave, cleansing solution, hair tonic, hair and body mist, facial serum, facial toner, deodorants, cleaning products like floor cleaner, hand dish wash, liquid detergents, room sprays etc.In order to improve the solubility of lipophilic substances, solubilizers are widely used. A solubilizer is an ingredient that helps solubilize, i.e. dissolve, an ingredient which is otherwise not or less soluble in the corresponding medium. An example where a solubilizer is often deemed appropriate is when an essential oil is to be incorporated in a water-based formulation. Other substances often solubilized in water-based preparations include fragrance oils and preservatives with oil soluble components, such as ethylhexylglycerin. Also many household preparations include solubilizers for dissolving functional lipophilic substances or fragrance components.Solubilizers are similar to emulsifiers in that they have both hydrophilic and lipophilic traits, but solubilizers tend to be completely water soluble and only slightly oil soluble. In practice this means they can suspend smaller amounts of oils. With a solubilizer, the dispersed phase has a particle size in the nanometer range and because they are solubilizing only small amounts of lipophilic active substances, the overall solution can still appear clear or lightly hazy.Usually essential oils, fragrance oils or preservatives with oil soluble components (such as benzyl alcohol) or other lipophilic active substances in water (or hydrosols) are solubilized. The concentration of the to-be solubilized ingredients is usually between 0.01 to 5.0 %.Dispersants are somewhere between solubilizers and emulsifiers. They can disperse very low concentrations of oils (such as vitamin E or even a triglyceride) in water. They don't completely solubilize the oil though; the product is not completely transparent. They disperse the oil in a translucent to milky solution which remains stable for a reasonable period of time.Apart from the appearance, there are safety and functional problems with such formulations. In a uniformly solubilized product, the lipophilic active ingredients are uniformly dispersed in the product as very small droplets and their concentration is exactlythe same through the whole solution from the very first splash to the very last ml till the bottle is completely empty. Without the use of a solubilizer the distribution of the lipophilic active ingredient, would be quite haphazardly in the solution and would vary from application to application.Many solubilizers are known. However, it is needless to say that there is not one solubilizer, which fits all needs. Moreover, many solubilizers have different negative side effects like increased foam formation. This behavior is undesired in non-surfactant-based formulations. Often they are based on ethoxylated fatty alcohols which have negative side effects on the skin since they increase the skin permeation.In addition, there is a general desire to replace existing substances by “green” or biobased alternatives. Hence, there is an ongoing demand for further substances which can improve the solubility of lipophilic substances in water based preparations, and thus, increase their availability in the preparations.Moreover, when searching for solubilizers it must be taken into account that substances used in regulated sectors must be toxicologically acceptable, well tolerated by the skin and stable within the matrix forming the preparation. In addition, it is preferred that the solubilizer is odorless or at least has a pleasant smell, cheap and readily available.However, there is no clear dependency between the chemical structure of a substance, on the one hand, and its capability in improving solubility, on the other hand, which makes the search for suitable substances difficult. Furthermore, there is no predictable relationship between solubility improvement, toxicological acceptability, tolerability and the stability of a substance.Against this background, it is an object of the present invention to provide means and methods for improving the solubility of lipophilic substances in water based preparations, thereby increasing their availability in the preparations. A further, optional, aim is that the solubility should be maintained over long time, preferably the shelf life of the product, and the (initial) turbidity should not increase over time, at least not substantially. A yet further aim is that the solubility improving means are environmentally friendly and compatible for the intended use including personal care use. Yet another object is that at least some of the above described negative aspects of commonly used solubilizers are overcome.The above objects are achieved by the various aspects of the present invention.A first aspect of the present invention pertains to the use of at least one of compounds of formula (I) as a solubilizer or a co-solubilizer of a lipophilic substance in a water based preparation.The compounds of formula (I) as described herein are defined as follows:wherein R is selected from the group of residues consisting of formulas l-a to l-f:.ln another aspect of the present invention, a method of improving the solubility of a lipophilic substance in a water based preparation comprises or consists of the following steps (a) to (d):(a) providing at least one of compounds of formula (I) as defined herein;(b) providing at least one lipophilic substance;(c) providing a water based base preparation; and(d) adding the at least one compound of step (a) to the at least one lipophilic substance of step (b) and the base preparation of step (c) in an amount effective to increase the solubility of the lipophilic substance in the water based preparation.Preferably, the use as a solubilizer or the increase of the solubility involves reducing turbidity of the preparation.A water based preparation forms a further aspect of the present invention. The water based preparation comprises the following constituents:(i) at least one of compounds of formula (I) as defined herein;(ii) a lipophilic substance; and(iii) water.Surprisingly it has been found that the addition of an effective amount of at least one of the compounds of formula (I) act as an efficient solubilizer / co-solubilizer for lipophilic substances in water based preparations. The lipophilic substances were further found to remain soluble over a long time and the preparation remained clear and non-turbid. Due to its better solubility, a uniformly solubilized preparation, in which the lipophilic substance is uniformly dissolved can be obtained. Thus, the concentration of the lipophilic substance remains the same until the preparation has been completely emptied by the used. Further, the compounds of formula (I) as described herein ease production of water based preparations. For instance, they render possible the cold preparation, i.e. no heating during preparation is necessary, and there is no need for countermeasures to avoid precipitation during production.In addition, the compounds of formula (I) are environmentally friendly and meet requirements for being integrated into personal care, including oral care, preparations and / or household preparations. In particular, the compounds of formula (I) aretoxicologically and dermatologically acceptable, odorless, and non-ethoxylated (not skin permeable).Formula (I) as defined above defines the following specific compounds:The term “lipophilic” refers to the ability of a chemical compound to dissolve in fats, oils, lipids and non-polar solvents such as hexane or toluene. Such non-polar solvents are themselves lipophilic. Thus, lipophilic substances tend to dissolve in other lipophilic substances, whereas hydrophilic substances tend to dissolve in water and other hydrophilic substances. Therefore, “lipophilic” substances are defined according to the present invention in that they are not soluble in water at room temperature (20°C) in a concentration of more than 0.01 % by weight. The water solubility of a substance is the saturation mass concentration of the substance in water at ambient temperature (20°C).The lipophilic substance is not necessarily one compound, but may also be a mixture of compounds, for instance a fragrance mixture. Further, the lipophilic substance may be characterized by a log PO / W value range of > 0 to 25.0. Preferably, the lipophilic active component has a log PO / W value range of > 0 to 20.0, more preferred a log PO / W value range of > 0 to 16.0, particularly preferred a log PO / W value range of > 0 to 5.0, calculated by EPISuite v4.40 (U.S. Environmental Protection Agency; calculated with KOWWINv1 .68). The higher the log PO / W value the poorer the solubility of the lipophilic substance in a water based preparation. More preferred is a log PO / W value range for the lipophilic active component from greater or equal to 1 .0 to less than or equal to 4.0.The log P value (or log Po / w) is a constant defined in the following manner: log P = Iog10 (partition coefficient). Partition Coefficient, P = [organic] / [aqueous], where [ ] indicates the concentration of solute in the organic and aqueous partition, in the present case in the 1- octane and water partition. A negative value for log P means the compound has a higher affinity for the aqueous phase (it is more hydrophilic). When log P = 0 the compound is equally partitioned between the lipid and aqueous phases. A positive value for log P denotes a higher concentration in the lipid phase (i.e. the compound is more lipophilic). Log P = 1 means there is a 10:1 partitioning in organic:aqueous phases.The term “at least one” as used herein means one or a mixture of two, three, four or five, or even more different of the respective components following said term. For example, the phrase “at least one of the compounds of formula (I)” provides for any one of the compounds as well as all possible combinations of two, three, four or five compounds of formula (I).Using the abbreviations shown in the above table as a placeholder for the respective compound, specific combinations of two compounds include the following:A+B, A+C, A+D, A+E, B+C, B+D, B+E, C+D, C+E and D+E.Specific combinations of three compounds of formula (I) include the following:A+B+C, A+B+D, A+B+E, A+C+D, A+C+E, A+D+E, B+C+D, B+C+E, B+D+E and C+D+E.Specific combinations of four compounds of formula (I) include the following:A+B+C+D, A+B+D+E, A+C+D+E and B+C+D+E.It is assumed that combinations of two, three, four or five compounds of formula (I) even further improve the solubility of a lipophilic substance as compared to the respective individual compounds of formula (I).The term “water-based preparation” denotes a preparation mainly constituted of water. This means, that water forms more than > 50 wt.-% of the preparation. For instance, the watercan form 60, 70, 80, 90, or even more than 90 wt.-% of the preparation. Preferably, the preparation is an aqueous, aqueous / alcoholic or aqueous / glycolic preparation.When referring to solubility herein, equilibrium (thermodynamic) solubility in water is meant. The equilibrium solubility of a compound is defined as the maximum quantity of that substance which can be completely dissolved at a given temperature (here, 25°C) and pressure (here, 1013 mPa) in a given amount of water (e.g., 100 mL), and is thermodynamically valid as long as a solid phase exists which is in equilibrium with the solution phase.The term “an amount effective to increase the solubility of the lipophilic substance in the water based preparation” means that a tangible solubility increase can be determined for the lipophilic substance in the water based preparation containing the compound of formula (I) as compared to a corresponding water based preparation lacking the compound of formula (I).The term “solubilizer” as used herein denotes an agent that improves the solubility of the lipophilic substance in water. If the solubility limit is exceeded, the solubilizer may still render a solution clear or lightly hazy as if the compound to be solubilized was completely solubilized. This happens when the compound to be solubilized is evenly dispersed, forming a droplet size in the nanometer range. In the present invention, the potential of the compounds of formula (I) to increase the amount at which a lipophilic substance can be evenly dispersed and form a droplet size in the nanometer range in the water based preparation, preferably in the range from 1 nm to 500 nm, more preferably in the range from 1 nm to 100 nm, most preferably in the range from 1 nm to 50 nm.Further aspects, embodiments and effects of the present invention will arise from the description below, which is understood to be generally applicable to all uses, methods and products (preparations) of the invention described herein, in particular from the examples, as well as from the attached patent claims.In the context of the present invention, the lipophilic substance can be a substance which imparts one or more than one benefit, functions or operate via more than one mode of action, such as anti-microbial, deodorant, fragrant, antioxidative, anti-inflammatory, antiitching, anti-redness, skin-caring, anti-dandruff, anti-perspirant, , hairgrowth strengthening, anti-dark-spot, anti-cellulite, anti-viral, anti-wrinkle, skin-whitening, skin tanning, painreducing, swelling reduction, skin barrier strengthening, anti-mycotic, anti-sagging, and skin soothing properties.In a preferred embodiment of the invention, the lipophilic substance is selected from the group consisting of 2-methyl 5-cyclohexylpentanol, dimethyl phenylbutanol, ethylhexylglycerin, caprylhydroxamic acid, tocopherol, bisabolol, o-cymen-5-ol, glyceryl caprylate, retinyl palmitate, retinol, farnesol, glyceryl laurate, hydroxyacetophenone, caffeine, undecylenoyl phenylalanine, phenylethyl resorcinol, hydroxymethoxyphenyl decanone, zingiber officinale (ginger) root extract, myristoyl nonapeptide-3, palmitoyl tripeptide-1 , palmitoyl tetrapeptide-7, palmitoyl pentapeptide-4, hydroxypinacolone retinoate, isochrysis galbana extract, sclareolide, vanillyl butylether, hydroxyphenyl propamidobenzoic acid, 4-t-butylcyclohexanol, ubiquinone-10, climbazole, aldehyd C12, lilial, dihydromyrcenol, globalide, linalyl Acetate, citronellylacetat, phenylethyl methylether, and mixtures of two or more of the aforesaid lipophilic agents.In order to further increase the solubility of the lipophilic substance, the preparation as defined herein can be combined with at least one solubilizer (different from compounds of formula (I)). The solubilizers which can be used in the present invention are preferably a PEG based or PEG free solubilizer. More preferably, the solubilizer is selected from the group consisting of PEG-40 Hydrogenated Castor Oil, Polysorbate- 20, 60 and 80, PEG-8, PEG-7 Glyceryl Cocoate, Decyl Glucoside, Ceteareth-20, Cetearyl Glucoside, PEG-60 Hydrogenated Castor Oil, Steareth-2, Steareth-20, PPG- 26-buteth-26, PPG-5-Laureth-5, Steareth-21 , Trideceth-9, PEG-32, Glycereth-26, Polyglyceryl-3 Distearate, Methyl Gluceth-20, PEG-12 Laurate, Polyglyceryl-4 Caprylate, Oleth-20, Oleth-2, Polyglyceryl-4 Caprate, PPG-1 -PEG-9 Lauryl Glycol Ether, Polyglyceryl-2 Caprate, lsoceteth-20, PPG- 13-decyltetradeceth-24, Sodium Cocoyl Glutamate, Sucrose Trilaurate, Sorbitan Sesqucaprlyate, Lauroyl Alanine, Heptyl Glucoside, Capryloyl / Caproyl Methyl Glucamide, Polyxyethylene sorbitan monolaurate, Polyxylene lauryl ether, PEG 400 monolaurate, sodium xylene sulfaonte, sodium cumene sulfonate, and mixtures of two or more of the aforementioned solubilizers.In a more preferred variant, the water-based preparation as described herein comprises a solubilizer selected from the group consisting of PEG-40 Hydrogenated Castor Oil, Polysorbate-20, 60 and 80, PEG-8, PEG-7 Glyceryl Cocoate, Decyl Glucoside, Ceteareth- 20, Cetearyl Glucoside, PEG-60 Hydrogenated Castor Oil, Steareth-2, Steareth-20, PPG- 26-buteth-26, PPG-5-Laureth-5, Steareth-21 , Trideceth-9, and mixtures of two or more of the aforementioned solubilizing agents. In a particularly preferred variant, the solubilizer contains or consists of PEG-40 Hydrogenated Castor Oil and / or Trideceth-9. In another particularly preferred variant, the solubilizer contains or consists of Polyglyceryl-4 Caprylate.The solubility of the lipophilic substance in water-based preparations may be further increased by combining the compound of formula (I), and optionally the further solubilizer, with at least one hydrophilic solvent. The hydrophilic solvent(s) which can be used in the present invention is preferably selected from the group consisting of Glycerin, Propylene Glycol, Butylene Glycol, Isopropyl Alcohol, Porpanediol, Dipropylene Glycol, Propylene Carbonate, Ethanol, Hexylene Glycol, Glycerin Carbonate, Methylpropanediol, Butylene Carbonate, Dimethly Isosorbide, or mixtures of two or more of the aforementioned hydrophilic solvents.Preferred preparations are aqueous, aqueous / alcoholic or aqueous / glycolic. The aqueous / alcoholic or aqueous / glycolic based preparations comprise an aliphatic alcohol or a glycol in an amount of 0.1 to < 50 % by weight, based on the total weight of the solution. The aliphatic alcohol is preferably selected from the group consisting of ethanol, isopropanol, n-propanol. The glycol is preferably selected from the group consisting of glycerin, propylene glycol, butylene glycol or dipropylene glycol. Preferably, the overall water content in the final composition of such compositions can be > 60 %, more preferably > 70 %, even more preferably > 80 %, and even more preferably > 90 %. Solutions for water wipes (wet wipes) have high water content. They may then contain > 95 % water, or even > 98 % water.It is further preferred that the preparation is transparent or semi-transparent.The advantages achieved by the present invention can be particularly well exploited in the case of personal care preparations and household preparations. Preferred personal care preparations and household preparations are formulated as creams, lotions, sticks, gels, solutions, wipes, masks, deodorants, shampoos, conditioners, micellar waters, sunscreens, dish washing liquids, all-purpose cleaners, liquid soaps, mouthwashes, and mouth sprays.For instance, in aqueous mouthwashes with low alcohol / ethanol content, the compounds of formula (I) ensure good solubility of the lipophilic substance. In particular, for systems that tend to recrystallize over time after solubilization the compounds of formula (I) are effective in preventing precipitation, and maintaining solubilization, of lipophilic substances such as o-Cymen-5-ol.Further reference is made to the example section where specific formulation-types are exemplified.Optional constituents of preparations as described herein include on or more of the following: abrasives, anti-acne agents, agents against ageing of the skin, anti-cellulitis agents, anti-dandruff agents, anti-inflammatory agents, anti-microbial agents, irritationpreventing agents, irritation-inhibiting agents, antioxidants, astringents, odor absorbers, perspiration-inhibiting agents, antiseptic agents, anti-statics, binders, buffers, carrier materials, chelating agents, cell stimulants, cleansing agents, depilatory agents, surfaceactive substances, deodorizing agents, antiperspirants, softeners, enzymes, enzyme inhibitors, essential oils, fibers, film-forming agents, fixatives, foam-forming agents, foam stabilizers, substances for preventing foaming, foam boosters, gelling agents, gel-forming agents, hair care agents, hair-setting agents, hair-straightening agents, moisture-donating agents, moisturizing substances, moisture-retaining substances, bleaching agents, strengthening agents, stain-removing agents, optically brightening agents, impregnating agents, dirt-repellent agents, dyes, friction-reducing agents, lubricants, moisturizing creams, ointments, opacifying agents, plasticizing agents, covering agents, polish, preservatives, gloss agents, green and synthetic polymers, powders, proteins, re-oiling agents, abrading agents, silicones, skin-soothing agents, skin-cleansing agents, skin care agents, skin-healing agents, skin-lightening agents, skin-protecting agents, skin-softening agents, hair promotion agents, cooling agents, skin-cooling agents, warming agents, skinwarming agents, stabilizers, surfactants, UV-absorbing agents, UV filters, primary sun protection factors, secondary sun protection factors, detergents, fabric conditioning agents, suspending agents, skin-tanning agents, actives modulating skin or hair pigmentation, matrix-metalloproteinase inhibitors, skin moisturizing agents, glycosaminoglycan stimulators, TRPV1 antagonists, desquamating agents, anti-cellulite agents or fat enhancing agents, hair growth activators or inhibitors, thickeners, rheology additives, vitamins, , fats, phospholipids, saturated fatty acids, mono- or polyunsaturated fatty acids, a-hydroxy acids, poly hydroxyfatty acids, liquefiers, dyestuffs, colour-protecting agents, pigments, anti-corrosives, fragrances or perfume oils, aromas, flavouring substances, odoriferous substances, polyols, electrolytes, organic solvents, and mixtures of two or more of the aforementioned substances.Preferred constituents of preparations as described herein include on or more of the following: agents against ageing of the skin, anti-microbial agents, antioxidants, chelating agents, surfactants, preservatives, green and synthetic polymers, skin-cooling agents, rheology additives, oils, fragrances, perfume oils, and polyols.Examples of the aforementioned optional and preferred constituents as well as further constituents that can be included in the preparations as described herein can be found in paragraphs

[0284] to

[0351] of WO2022 / 122935.In preferred embodiments, the preparation comprises the at least one compound of formula (I) in an amount of 0.01 to 10 wt.-%, preferably 0.05 to 2.5 wt.-%, more preferably 0.1 to 1.0 wt.-%, based on the total weight of the preparation. In this range, a profound solubility increase is observed, resulting in a stable preparation that remains clear and non-turbid over long time. The solubility increase, as compared to a corresponding preparation lacking the compound of formula (I), may be at least 5, at least 10, at least 15, at least 20, at least 25, at least 30, at least 35, at least 40, at least 45, at least 50, or even more than 50%.In specific embodiments, the water and the at least one compound of formula (I) is included in the preparation in a weight ratio of 10,000:1 to 10:1 , preferably 5,000:1 to 100:1 , more preferably 2,000:1 to 200:1. Further, the at least one compound of formula (I) and the at least one lipophilic substance is contained in a weight ratio of 1 :100 to 50:1 , preferably 1 :50 to 10:1 , more preferably 1 :20 to 5:1 , most preferably 1 :10 to 1 :1 .While the preceding description was made on the basis of compounds of formula (I), the compounds of formula (I) are to be understood as preferred compounds of the present disclosure only, and the aspects, embodiments, features and effects described in conjunction with the compounds of formula (I) are to be understood to be correspondingly applicable to the compounds of the present disclosure. This means, for instance, that the compounds of formula (II) can be used for the purposes, in the methods or in the preparations, as described herein in place of the compounds of formula (I). It likewise means, for example, that in preferred compounds of formula (II), X is as defined in formula (I), or that preferred preparations may comprise the compounds of formula (II) in the same amount as described for the compounds of formula (I).The compounds of formula (II) are defined as follows:with n = 1 -10, preferably n = 2-10, more preferably 3-10, wherein X is:• straight-chain C5 - Cu, preferably Ce - Cu, more preferably C7 - C13, yet more preferably Cs - C12, most preferably C9 - Cn, alkyl or alkenyl; orselected from the group consisting of:with R3being -OCH3, -OCH2CH3, or -O(CH2)2CH3, wherein if n = 1 :R1is selected from the group consisting of -H and -OH, and R2is selected from the group consisting of -H, -CH2(OH), -CH(OH)-CH2(OH), and -CH(OH)-CH(OH)- CH2(OH); or• R1is -OH, and R2and the -OH group shown in formula (II) are joined together to form the following compound of formula (I l-a):• R1and R2are joined together to form the following compound of formula (I l-b):wherein if n = 2-10, R1is -OH, and R2= -H.When(as defined above) can be on any one of the free carbon atoms of the benzyl ring, i.e. X can be selected from the group consisting of:The compounds of formulae (I) are accessible not only via precursors of petrochemical origin, but advantageously also in a sustainable and / or cost-efficient way from biobased starting materials comprising only non-fossil fuel-based carbon. Assessment of the biobased carbon in a material can be performed through standard test methods. Using radiocarbon and isotope ratio mass spectrometry analysis, the biobased content of materials can be determined. ASTM International, formally known as the American Society for Testing and Materials, has established a standard test method for assessing the biobased content of materials. The ASTM method is designated ASTM D6866. According to a preferred embodiment of the present invention, more than 50% of the carbon atomscontained in a compound of formula (I) are biobased, based on the total number of carbon atoms contained in said compound of formula (I). More preferably, more than 60%, 70%, 75%, 80%, 85%, or 90% of the carbon atoms contained in a compound of formula (I) are biobased, based on the total number of carbon atoms contained in said compound of formula (I). The same is true for compounds of formula (II).The present invention is further described with reference to the following examples, which are merely illustrative for, but do not limit, the present invention.Examples:1 . Materials1.1 Lipophilic ingredientsThe lipophilic ingredients tested included 2-methyl 5-cyclohexylpentanol, dimethyl phenylbutanol, ethylhexylglycerin, caprylhydroxamic acid, Fragrance 1 (Product code482105) Citrus Fresh NX Perfume, Fragrance 2 (Product code 816918) Classico Power NX Perfume. Fragrances 1 and 2 are complex fragrance mixtures that have low solubility in water.1 .2 3-HydroxypropylestersThe following 3-Hydroxypropylester have been used in the experiments:The compounds of formulae (I) and (II) can be obtained, for instance, by following the synthetic approaches described in Synthesis, 2003, (15), 2373-2377; Journal of the Korean Chemical Society, 2002, 46(5); Tetrahedron Letters, 2015, 56(15), 1973-1975; and JP2011207990A.2. Sample preparation and evaluation2.1 Liquid lipophilic ingredientsThe samples were prepared as follows: Premix lipophilic ingredient and the respective 3- hydroxypropylester with glycol and solubilizer. Heat up to 60°C while stirring. Add Water and stir for additional 10 minutes. Evaluate turbidity 24h after preparation.Samples were analyzed via visual evaluation and characterized using the following scale.Turbidity was measured in triplicates via TURB IR430 ex WTW with NephelometricTurbidity Unit (NTU)2.2 Caprylhydroxamic acid (solid lipophilic ingredient)Samples were prepared by the following protocol: Premix caprylhydroxamic acid and the respective 3-hydroxypropylester with glycol and solubilizer. Heat up to 60°C while stirring. Add Water and stir for additional 10 minutes. Filtrate crystals after 24h storage at room temperature (20 to 25°C). Dry filter and crystals for 24h at 40°C.3. Results3.1 2-Methyl 5-Cyclohexylpentanol a) In combination with PEG based solubilizer:Less turbidity (visual and measured) with the tested 3-Hydroxypropylesters compared toPlacebo (no 3-Hydroxypropylester) was observed. It was concluded that solubility of 2-Methyl 5-Cyclohexylpentanol in aqueous solution can be improved by addition of the hydroxypropylesters. b) In combination with PEG free solubilizer:3.2 Dimethyl PhenylbutanolLess turbidity (visual and measured) with Hydroxypropylesters compared to Placebo.Solubility of Dimethyl Phenylbutanol in aqueous solution can be improved by the esters.3.3 EthylhexylglycerinLess turbidity (visual and measured) with Hydroxypropylesters compared to Placebo. Solubility of Dimethyl Ethylhexylglycerin in aqueous solution can be improved by the esters.3.4 Caprylhydroxamic acidThe addition of Propanediol Caprylate leads to less recrystallization of Caprylhydroxamic acid compared to Placebo.3.5 Fragrance 1 Citrus Fresh NX Parfum3.6 Fragrance 2 Classico Power NX Parfum4. Formulation examplesIn the following examples, the amounts are indicated as % by weight for all formulations..1 DEO .1.1 Deodorant Spray with ACH.1.2 Cool Relief Deo Plus.1.3 Sport Fit Deo.1.4 Deodorant stick.1.5 Antiperspirant stick.1 .6 Deodorant formulation in the form of a roll-on gel4.1 .7 Clear deo anti-perspirant roll-on4.2 GEL 4.2.1 After Shave Tonic.2.2 Cold & Hot Firming GEL with Thermolat & Frescolat.2.3 Frosty Facial Foam.2.4 Hydration Face Gel, water clear.2.5 Intimate Sensi-Gel.2.6 Mild feminine wash.2.7 Biotic Acne Control Gel.2.8 Anti-wrinkle gel.2.9 Cleansing Micellar Gel.2.1 OSprayable Anti Cellulite Gel.3 WIPES .3.1 PEG-free Wet Wipe.3.2 Intimate Wipes.4 ORAL CARE .4.1 Protective Mouth Rinse.4.2 Mouthwash (Ready to use) without alcohol.4.3 Mouthwash concentrate.4.4 Refresh your Breath Mouthspray.5 MASKS .5.1 Sheet mask - New Skin.5.2 Sheet mask- Ultra Calming.5.3 Watermelon Face Mask & Scrub.6 HOMECARE .6.1 Floor Cleaner with gloss.6.2 Simple floor cleaner

Claims

Claims:1 . Use of at least one of compounds of formula (I)wherein R is selected from the group consisting of:as a solubilizer or a co-solubilizer of a lipophilic substance in a water based preparation.

2. Method of improving the solubility of a lipophilic substance in a water based preparation, comprising or consisting of:(a) providing at least one of compounds of formula (I) as defined in claim 1 ;(b) providing at least one lipophilic substance;(c) providing a water based base preparation; and(d) adding the at least one compound of (a) to the at least one lipophilic substance of (b) and the base preparation of (c) in an amount effective to increase the solubility of the lipophilic substance in the water based preparation.

3. Water based preparation, comprising(i) at least one of compounds of formula (I) as defined in claim 1 ;(ii) a lipophilic substance; and(iii) water.

4. Preparation of claim 3, wherein the lipophilic substance is selected from the group consisting of 2-methyl-5-cyclohexylpentanol, dimethyl phenylbutanol, ethylhexylglycerin, caprylhydroxamic acid, tocopherol, bisabolol, o-cymen-5-ol, glyceryl caprylate, retinyl palmitate, retinol, farnesol, glyceryl laurate, hydroxyacetophenone, caffeine, undecylenoyl phenylalanine, phenylethyl resorcinol, hydroxymethoxyphenyl decanone, zingiber officinale (ginger) root extract, myristoyl nonapeptide-3, palmitoyl tripeptide-1 , palmitoyl tetrapeptide-7, palmitoyl pentapeptide-4, hydroxypinacolone retinoate, isochrysis galbana extract, sclareolide, vanillyl butylether, hydroxyphenyl propamidobenzoic acid, 4-t- butylcyclohexanol, ubiquinone-10, climbazole, aldehyd C12, lilial, dihydromyrcenol, globalide, linalyl Acetate, citronellylacetat, phenylethyl methylether, and mixtures of two or more of the aforesaid lipophilic agents.

5. Preparation of claim 3 or 4, further comprising a PEG based or PEG free solubilizer.

6. Preparation of claim 5, wherein the PEG based or PEG free solubilizer is selected from the group consisting of PEG-40 Hydrogenated Castor Oil, Polysorbate- 20, 60and 80, PEG-8, PEG-7 Glyceryl Cocoate, Decyl Glucoside, Ceteareth-20, Cetearyl Glucoside, PEG-60 Hydrogenated Castor Oil, Steareth-2, Steareth-20, PPG- 26- buteth-26, PPG-5-Laureth-5, Steareth-21 , Trideceth-9, PEG-32, Glycereth-26, Polyglyceryl-3 Distearate, Methyl Gluceth-20, PEG-12 Laurate, Polyglyceryl-4 Caprylate, Oleth-20, Oleth-2, Polyglyceryl-4 Caprate, PPG-1 -PEG-9 Lauryl Glycol Ether, Polyglyceryl-2 Caprate, lsoceteth-20, PPG-13-decyltetradeceth-24, Sodium Cocoyl Glutamate, Sucrose Trilaurate, Sorbitan Sesqucaprlyate, Lauroyl Alanine, Heptyl Glucoside, Capryloyl / Caproyl Methyl Glucamide, Polyxyethylene sorbitan monolaurate, Polyxylene lauryl ether, PEG 400 monolaurate, sodium xylene sulfaonte, sodium cumene sulfonate, and mixtures of two or more of the aforementioned solubilizers.

7. Preparation of claim 6, wherein the PEG based solubilizer contains or consists of PEG-40 Hydrogenated Castor Oil and / or Trideceth-9.

8. Preparation of claim 6, wherein the PEG free solubilizer contains or consists of Polyglyceryl-4 Caprylate.

9. Preparation of any of claims 3 to 8, further comprising a hydrophilic solvent.

10. Preparation of claim 9, wherein the hydrophilic solvent is selected from the group consisting of Glycerin, Propylene Glycol, Butylene Glycol, Isopropyl Alcohol, Porpanediol, Dipropylene Glycol, Propylene Carbonate, Ethanol, Hexylene Glycol, Glycerin Carbonate, Methylpropanediol, Butylene Carbonate, Dimethly Isosorbide, or mixtures of two or more of the aforementioned hydrophilic solvents.11 . Preparation of any of claims 3 to 10, wherein the preparation is one or more of: mainly constituted of water, preferably wherein the preparation is an aqueous, aqueous / alcoholic or aqueous / glycolic preparation, transparent or semi-transparent; selected from the group consisting of personal care preparations and household preparations, preferably creams, lotions, sticks, gels, solutions, wipes, masks, deodorants, shampoos, conditioners, sunscreens, micellar waters, dish washing liquids, all-purpose cleaners, liquid soaps, mouthwashs, and mouthsprays.

12. Preparation of any of claims 3 to 11 , comprising the at least one compound of formula (I) in an amount of 0.01 to 10 wt.-%, preferably 0.05 to 2.5 wt.-%, more preferably 0.1 to 1 .0 wt.-%, based on the total weight of the preparation.

13. Preparation of any of claims 3 to 12, comprising the water and the at least one compound of formula (I) in a weight ratio of 10,000:1 to 10:1 , preferably 5,000:1 to100:1 , more preferably 2,000:1 to 200:1 , and / or comprising the at least one compound of formula (I) and the at least one lipophilic substance in a weight ratio of 1 :100 to 50:1 , preferably 1 :50 to 10:1 , more preferably 1 :20 to 5:1 , most preferably 1 :10 to 1 :1 .

14. Use of claim 1 or method of claim 2, wherein the use as a solubilizer or the increase of the solubility involves reducing turbidity of the preparation.

15. Use of claim 1 or 14, or method of claim 2 or 14, wherein the preparation is as defined in any of claims 3 to 13.

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