KR20260040605A - 3-hydroxypropyl ester as a solubility enhancer for lipophilic components - Google Patents

Abstract

The present invention relates to the use of at least one of the compounds represented by formula (I) as a solubilizing agent or auxiliary solubilizing agent for lipophilic substances in aqueous formulations.

Description

3-hydroxypropyl ester as a solubility enhancer for lipophilic components

The present invention relates primarily to the use of lipophilic substances as solubilizers or auxiliary solubilizers in 3-hydroxypropyl esters and aqueous formulations. The present invention is one of a series of inventions relating to 3-hydroxypropyl esters and structurally related compounds, jointly filed as PCT patent applications by the same applicant on the same filing date, wherein the PCT patent applications are respectively "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," and "3-hydroxypropylesters as antimicrobial agents." They are titled as “antimicrobial agents” and “Antimicrobial synergies”, and the contents of these applications are incorporated herein by reference.

Personal care formulations, including cosmetic and dermatological pharmaceutical formulations, are aqueous complex mixtures intended primarily for topical application. Many of these contain substances with significant lipophilic properties. In fact, a broad spectrum of lipophilic substances are used in a wide range of personal care formulations to provide various functions such as anti-inflammatory, anti-itching, anti-redness, anti-dandruff, antimicrobial, anti-perspirant, anti-cellulite, antiviral, antioxidant, anti-wrinkle, skin whitening, skin tanning, pain reduction, swelling reduction, skin barrier strengthening, anti-mycotic, anti-sagging, deodorizing, and skin soothing properties.

A disadvantage of using lipophilic functional substances is their low water solubility. Due to this property, it is particularly difficult to incorporate them into formulations composed primarily of water, including water-based/alcoholic and water-based/glycolic formulations, which often serve as the basis for liquid soaps, shampoos, and gels. Furthermore, for lipophilic substances, it is also difficult to formulate clear and non-turbid formulations such as solutions for wet wipes, micellar water, mouthwash, aftershave solution, cleansing solution, hair tonic, hair and body mist, facial serum, facial toner, deodorant, cleaning products like floor cleaner, hand dishwashing detergent, liquid detergent, and room spray.

Solubilizers are widely used to improve the solubility of lipophilic substances. A solubilizer is a component that helps to solubilize, or dissolve, ingredients that are otherwise insoluble or have low solubility in the medium. An example where solubilizers are often considered appropriate is when essential oils are to be incorporated into aqueous formulations. Other substances solubilized in aqueous formulations include fragrance oils and preservatives containing oil-soluble components such as ethylhexylglycerin. Additionally, many household formulations contain solubilizers to dissolve functional lipophilic substances or fragrance components.

Solubilizers are similar to emulsifiers in that they possess both hydrophilic and lipophilic properties; however, solubilizers tend to dissolve completely in water but only slightly in oil. In practice, this means that solubilizers can maintain a small amount of oil in a suspension state. When using solubilizers, the dispersed phase has a particle size in the nanometer range, and since it solubilizes only a small amount of the lipid-soluble active ingredient, the overall solution may still appear transparent or show only slight turbidity.

Typically, essential oils, fragrance oils, or preservatives containing fat-soluble components (such as benzyl alcohol), or other fat-soluble active ingredients are solubilized in water (or hydrosol). The concentration of the solubilized component is typically 0.01% to 5.0%.

Dispersants have characteristics intermediate between solubilizers and emulsifiers. They can disperse oils, such as vitamin E or even triglycerides, in water at very low concentrations. However, they do not completely solubilize the oil, and consequently, the product is not completely transparent. They disperse the oil into a translucent to milky white solution that remains stable for a reasonable period.

Apart from appearance, these formulations present safety and functional issues. In uniformly solubilized products, the lipophilic active ingredient is uniformly dispersed within the product as very small droplets, and its concentration remains exactly the same throughout the solution from the initial dispensing volume to the final mL until the bottle is completely emptied. Without the use of a solubilizer, the distribution of the lipophilic active ingredient within the solution will be considerably random and will vary with each application.

Numerous solubilizers are known. However, it is evident that no single solubilizer exists to meet all requirements. Furthermore, many solubilizers exhibit various negative side effects, such as increased foaming. This behavior is undesirable in non-surfactant-based formulations. These are often based on ethoxylated fatty alcohols, which have negative side effects on the skin because they increase skin permeability.

Furthermore, there is a general demand to replace existing materials with “eco-friendly” or bio-based substitutes. Consequently, there is a continuous demand for additional materials that can improve the solubility of lipophilic substances in aqueous formulations, thereby increasing the availability of these substances within such formulations.

Furthermore, when searching for solubilizers, it should be considered that the substance used in the regulated field must be toxicologically acceptable, have good tolerance to the skin, and be stable within the matrix forming the formulation. Additionally, it is desirable that the solubilizer be odorless or at least have a pleasant odor, be inexpensive, and be readily available.

However, since there is no clear dependency between a substance's chemical structure and its ability to improve solubility, it is difficult to identify a suitable substance. Furthermore, there is no predictable relationship between solubility improvement, toxicological acceptability, tolerability, and substance stability.

Against this backdrop, the object of the present invention is to increase the availability of said formulations by providing means and methods for improving the solubility of lipophilic substances in aqueous formulations. Additionally, an optional object is that the solubility should be maintained for a long period, preferably throughout the shelf life of the product, and that the (initial) turbidity should not increase over time, or at least not increase substantially. Another object is that the means for improving solubility is environmentally friendly and suitable (compatible) for intended uses, including personal care applications. Another object is that at least some of the negative aspects of the commonly used solubilizers described above are eliminated.

The above objective is achieved by various embodiments of the present invention.

A first aspect of the present invention relates to using at least one of the compounds of formula (I) as a solubilizing agent or auxiliary solubilizing agent for a lipophilic substance in an aqueous preparation.

The compound of formula (I) described in this specification is defined as follows:

Here, R is selected from the group of residues consisting of equations I-a to I-f:

and

In another aspect of the present invention, a method for improving the solubility of a lipophilic substance in an aqueous formulation comprises the following steps (a) to (d) or is composed of the following steps (a) to (d):

(a) Providing at least one of the compounds of formula (I) as defined in this specification;

(b) providing at least one lipophilic substance;

(c) Providing a water-based base formulation; and

(d) adding at least one of the compounds of formula (I) of step (a) to the lipophilic substance of step (b) and the base preparation of step (c) in an amount effective for increasing the solubility of the lipophilic substance in the aqueous preparation.

Preferably, use as a solubilizing agent or increase in solubility entails reducing the turbidity of the preparation.

An aqueous formulation constitutes another aspect of the present invention. The aqueous formulation comprises the following components:

(i) At least one of the compounds of formula (I) as defined in this specification;

(ii) lipophilic substances; and

(iii) Water.

Surprisingly, it was found that adding an effective amount of at least one of the compounds of Formula (I) acts as an efficient solubilizer/auxiliary solubilizer for lipophilic substances in aqueous formulations. Furthermore, it was found that the lipophilic substances remain dissolved for a long period, and the formulations remain clear and turbid. Due to superior solubility, a uniformly solubilized formulation in which the lipophilic substances are uniformly dissolved can be obtained. Therefore, the concentration of the lipophilic substances remains constant until the formulation is completely used. Additionally, the compounds of Formula (I) described herein facilitate the preparation of aqueous formulations. For example, they enable non-heating formulation, meaning that heating is not required during the formulation process, and no measures are needed to prevent precipitation during production.

In addition, the compound of Formula (I) is environmentally friendly and meets the requirements for application in personal care formulations, including oral care, and/or household formulations. In particular, the compound of Formula (I) is toxicologically and dermatologically acceptable, odorless, and not ethoxylated (non-skin permeable).

Formula (I) defined above defines the following specific compounds:

The term “lipophilic” refers to the ability of a compound to dissolve in fats, oils, lipids, and non-polar solvents such as hexane or toluene. These non-polar solvents themselves are also lipophilic. Therefore, lipophilic substances tend to dissolve in other lipophilic substances, and hydrophilic substances tend to dissolve in water and other hydrophilic substances. Accordingly, according to the present invention, a “lipophilic” substance is defined as a substance that does not dissolve in water at a concentration exceeding 0.01 weight% at room temperature (20°C). The water solubility of a substance is the saturated mass concentration of the substance in water at room temperature (20°C).

The lipophilic substance does not necessarily have to be a single compound and may be a mixture of compounds, such as a fragrance mixture, for example. Additionally, the lipophilic substance may be characterized by having a log PO/W value in the range of 0 to 25.0. Preferably, the lipophilic active ingredient has a log PO/W value of 0 to 20.0, more preferably 0 to 16.0, and particularly preferably 0 to 5.0. This value is calculated using EPISuite v4.40 (U.S. Environmental Protection Agency; using KOWWIN v1.68). The higher the log PO/W value, the lower the solubility of the lipophilic substance in the aqueous formulation. More preferably, the log PO/W value range of the lipophilic active ingredient is 1.0 to 4.0.

The log P value (or log P _O/W ) is a constant defined as follows: log P = log 10 (partition coefficient). The partition coefficient P = [organic phase]/[aqueous phase], where [] represents the solute concentrations in the organic phase and the aqueous phase. In this case, it refers to the partition system between 1-octane and water. If the log P value is negative, the compound has a higher affinity for the aqueous phase (i.e., is more hydrophilic). If log P = 0, the compound is evenly distributed between the organic phase and the aqueous phase. If the log P value is positive, the compound has a higher concentration in the organic phase (i.e., is more lipophilic). log P = 1 means that the distribution between the organic phase and the aqueous phase is 10:1.

As used herein, the term “at least one” means one of each component listed following the term, or a mixture of two, three, four, five, or more different components. For example, the phrase “at least one of the compounds of Formula (I)” includes not only any one of the compounds of Formula (I), but also all possible combinations of two, three, four, or five compounds of Formula (I).

When the abbreviations listed in the table above are used as indicators for each compound, the specific combinations of the two compounds are as follows:

A+B, A+C, A+D, A+E, B+C, B+D, B+E, C+D, C+E and D+E.

The specific combinations of the three compounds of formula (I) are as follows:

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.

The specific combinations of the four compounds of Formula (I) are as follows:

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) further enhance the solubility of lipophilic substances compared to each individual compound of formula (I).

The term “aqueous formulation” means a formulation composed mainly of water. This means that water constitutes more than 50 weight percent of the formulation. For example, water may constitute 60 weight percent, 70 weight percent, 80 weight percent, 90 weight percent, or more than 90 weight percent of the formulation. Preferably, the formulation is an aqueous, aqueous/alcoholic, or aqueous/glycolic formulation.

When solubility is referred to in this specification, it means equilibrium (thermodynamic) solubility in water. The equilibrium solubility of a compound is defined as the maximum amount of the substance that can be completely dissolved in a given amount of water (e.g., 100 mL) at a given temperature (here, 25°C) and pressure (here, 1013 mPa), and is thermodynamically valid as long as there is a solid phase in equilibrium with the solution phase.

The term “an amount effective for increasing the solubility of a lipophilic substance in an aqueous formulation” means that the solubility of a lipophilic substance in an aqueous formulation containing the compound of formula (I) increases to a measurable degree compared to a corresponding aqueous formulation not containing the compound of formula (I).

As used herein, the term “solubilizing agent” refers to a formulation that improves the solubility of a lipophilic substance in water. Even if the solubility limit is exceeded, the solubilizing agent can keep the solution clear or slightly cloudy as if the compound to be solubilized were completely solubilized. This occurs when the compound to be solubilized is uniformly dispersed to form droplet sizes in the nanometer range. In the present invention, the compound of formula (I) has the potential to increase the amount of a lipophilic substance that can be uniformly dispersed in an aqueous formulation to form droplet sizes in the nanometer range, said droplet sizes preferably in the range of 1 nm to 500 nm, more preferably 1 nm to 100 nm, and most preferably 1 nm to 50 nm.

Further aspects, embodiments, and effects of the present invention will become apparent from the description below (particularly the examples) and the appended claims, and the description below is understood to apply generally to all uses, methods, and products (formulations) of the invention as described herein.

In the context of the present invention, the lipophilic substance may be a substance that provides one or more benefits or functions, such as antimicrobial, deodorizing, fragrance imparting, antioxidant, anti-inflammatory, anti-itching, anti-redness, skin care, anti-dandruff, anti-perspirant, hair strengthening, anti-dark-spot inhibition, anti-cellulite, antiviral, anti-wrinkle, skin whitening, skin tanning, pain reduction, swelling reduction, skin barrier strengthening, anti-mycotic, anti-sagging, and skin soothing properties, or acts through one or more mechanisms of action.

In a preferred embodiment of the present invention, the lipophilic substance is 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 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, It is selected from the group consisting of ubiquinone-10, climbazole, aldehyde C12, lilial, dihydromyrcenol, globalide, linalyl acetate, citronelly acetate, phenylethyl methyl ether, and a mixture of two or more lipophilic agents.

To further improve the solubility of lipophilic substances, the aqueous formulations defined herein may be used in combination with at least one solubilizing agent different from the compound of formula (I). The solubilizing agents that can be used in the present invention are preferably PEG-based solubilizing agents or PEG-free solubilizing agents. More preferably, the solubilizer is PEG-40 Hydrogenated Castor Oil, Polysorbate 20, Polysorbate 60 and Polysorbate 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 Polyglyceryl-2 Caprate, Isoceteth-20, PPG-13-decyltetradeceth-24, Sodium Cocoyl Glutamate, Sucrose Trilaurate, Sorbitan Sesquicaprylate, Lauroyl Alanine, Heptyl Glucoside, Capryloyl/Caproyl Methyl Glucamide, Polyoxyethylene Sorbitan Monolaurate, Polyoxyethylene Lauryl Ether, PEG-400 Monolaurate, Sodium It is selected from the group consisting of sodium xylene sulfonate, sodium cumene sulfonate, and a mixture of two or more of the above solubilizing agents.

In a more preferred variation, the aqueous formulations described herein comprise PEG-40 hydrogenated castor oil, polysorbate-20, polysorbate-60 and polysorbate-80, PEG-8, PEG-7 glyceryl cocoate, decyl glucoside, ceteareth-20, cetearyl glucoside, PEG-60 hydrogenated castor oil, steareth-2, steareth-20, and PPG-26-buteth-26. It comprises a solubilizer selected from the group consisting of PPG-5-Laureth-5, Steareth-21, Trideceth-9, and mixtures of two or more of the above solubilizers. In a particularly preferred variant, the solubilizer comprises or consists of PEG-40 Hydrogenated Castor Oil and/or Trideceth-9. In another particularly preferred variant, the solubilizer comprises or consists of polyglyceryl-4 caprylate.

The solubility of a lipophilic substance in an aqueous formulation can be further improved by using the compound of formula (I) and optionally an additional solubilizing agent in combination with at least one hydrophilic solvent. The hydrophilic solvents that can be used in the present invention are preferably selected from the group consisting of glycerin, propylene glycol, butylene glycol, isopropyl alcohol, propanediol, dipropylene glycol, propylene carbonate, ethanol, hexylene glycol, glycerin carbonate, methylpropanediol, butylene carbonate, dimethyl isosorbide, or a mixture of two or more of the above hydrophilic solvents.

Preferred formulations are aqueous, aqueous/alcoholic, or aqueous/glycolic. Aqueous/alcoholic or aqueous/glycolic formulations contain an aliphatic alcohol or glycol in an amount of at least 0.1% by weight and no more than 50% by weight based on the total weight of the solution. The aliphatic alcohol is preferably selected from the group consisting of ethanol, isopropanol, and n-propanol. The glycol is preferably selected from the group consisting of glycerin, propylene glycol, butylene glycol, or dipropylene glycol. Preferably, the total water content in the final composition of such a composition may be 60% or more, more preferably 70% or more, even more preferably 80% or more, and even more preferably 90% or more. Solutions for wet wipes (wet tissues) have a high water content. In that case, they may contain 95% or more water, or even 98% or more water.

In addition, it is desirable that the preparation be transparent or translucent.

The advantages achieved by the present invention can be particularly advantageously utilized in personal care formulations and household formulations. Preferred personal care formulations and household formulations are formulated in the form of creams, lotions, sticks, gels, solutions, wipes, masks, deodorants, shampoos, conditioners, micellar waters, sunscreens, dishwashing liquids, multi-purpose cleaners, liquid soaps, mouthwashes, and oral sprays.

For example, in aqueous mouthwashes with low alcohol/ethanol content, the compound of Formula (I) ensures excellent solubility of lipophilic substances. In particular, for systems that tend to recrystallize over time after solubilization, the compound of Formula (I) is effective in preventing the precipitation of lipophilic substances such as o-cymen-5-ol and maintaining the solubilized state.

Also, refer to the section on examples where specific formulation types are exemplified.

Optional components of the formulations described herein may include one or more of the following: abrasives, anti-acne agents, skin anti-aging agents, anti-cellulite agents, anti-dandruff agents (anti-dandruff agents), anti-inflammatory agents, antimicrobial agents, anti-irritation agents, irritation inhibitors, antioxidants, astringents, odor absorbers, antiperspirants, disinfectants, antistatic agents, binders, buffers, carriers, chelating agents, cell stimulants, cleansers, depilatories, surfactants, deodorizers, antiperspirants, emollients, enzymes, enzyme inhibitors, essential oils, fibers, film-forming agents, fixatives, foam-forming agents, foam stabilizers, anti-foaming agents, foam enhancers, gelling agents, gel-forming agents, hair care agents, hair setting agents, hair straightening agents, moisturizers, moisturizing substances, moisture retainers, bleaches, strengtheners, stain removers, optical whitening agents, impregnating agents, antifouling agents, dyes, friction reducers, lubricants, moisturizing creams, Ointments, opacifiers, plasticizers, coatings, glosses, preservatives, natural and synthetic polymers, powders, proteins, re-maintainers, abrasives, silicones, skin soothing agents, skin cleansers, skin care agents, skin healing agents, skin whitening agents, skin protectants, skin emollients, hair growth promoters, coolants, skin coolants, warmers, skin warmers, stabilizers, surfactants, UV absorbers, UV filters, primary UV protection factors, secondary UV protection factors, detergents, fabric conditioning agents, suspending agents, skin tanning agents, active ingredients that regulate pigment formation in skin or hair, matrix metalloproteinase inhibitors, skin moisturizers, glycosaminoglycan stimulants, TRPV1 antagonists, exfoliants, anti-cellulite agents or lipid enhancers, hair growth activators or inhibitors, thickeners, rheological additives, vitamins, fats, phospholipids, saturated fatty acids, monounsaturated or polyunsaturated fatty acids, α-hydroxy acids, Polyhydroxy fatty acid (multi-hydroxy fatty acid), liquefying agent, coloring agent, color protectant, pigment, corrosion inhibitor, fragrance or fragrance oil, aroma, flavor substance, aromatic substance, polyol, electrolyte, organic solvent, and a mixture of two or more of the above substances.

Preferred components of the formulations described herein may include one or more of skin anti-aging agents, antimicrobial agents, antioxidants, chelating agents, surfactants, preservatives, natural and synthetic polymers, skin coolants, rheological additives, oils, fragrances, fragrance oils, and polyols.

Examples of the above-mentioned optional and preferred components, and examples of other components that may be included in the formulations described herein, are described in paragraphs [0284] through [0351] of WO2022/122935.

In a preferred embodiment, the formulation contains at least one of the compounds of Formula (I) in an amount of 0.01 to 10 weight% based on the total weight of the formulation, preferably 0.05 to 2.5 weight%, and more preferably 0.1 to 1.0 weight%. Within this range, a significant increase in solubility is observed, and as a result, the formulation becomes a stable formulation that remains clear and turbid for a long period. Compared to a corresponding formulation that does not contain the compound of Formula (I), the rate of increase in solubility 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 may exceed 50%.

In a specific embodiment, water and at least one of the compounds of formula (I) are 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. Additionally, at least one of the compounds of formula (I) and at least one of the lipophilic substances are included 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.

Although the foregoing description is based on the compound of Formula (I), it should be understood that the compound of Formula (I) is merely a preferred compound of the present disclosure, and that the modes, embodiments, features, and effects described in relation to the compound of Formula (I) are correspondingly applicable to the compounds of the present disclosure. This means, for example, that the compound of Formula (II) may be used in place of the compound of Formula (I) for the purposes described herein, in the methods described herein, or in the preparations described herein. Furthermore, this means that, for example, X in the preferred compound of Formula (II) is as defined in Formula (I), or that the preferred preparation may contain the compound of Formula (II) in the same amount as described for the compound of Formula (I).

The compound of formula (II) is defined as follows:

n = 1 to 10, preferably n = 2 to 10, more preferably 3 to 10, and

Here, X is :

It is a straight-chain _C5 to _C14 , preferably _C6 to _C14 , more preferably _C7 to _C13 , even more preferably _C8 to _C12 , most preferably _C9 to _C11 alkyl or alkenyl; or

Selected from the group consisting of the following;

, or

Here, ^R3 is _-OCH3 , _{-OCH2CH3 ,} or -O( _CH2 ) _2CH3 , _and

However, for the case where n = 1:

^R1 is selected from the group consisting of -H and -OH, and ^R2 is selected from the group consisting of -H, _-CH2 (OH), -CH(OH) _-CH2 (OH), and -CH(OH)-CH(OH) _-CH2 (OH); or

^R1 is -OH, and ^R2 and the -OH group indicated in Formula (II) combine to form a compound of Formula (II-a) below;

; or

^R1 and ^R2 combine together to form a compound of the following formula (II-b), and

;

However, for n = 2 to 10, ^R1 is -OH and ^R2 is -H.

X is In this case, ^R3 (defined above) can be located on any of the substitutable carbon atoms of the benzyl ring, i.e., X can be selected from the group consisting of the following:

The structures of particular interest are as follows:

The compound of Formula (I) can be advantageously obtained in a sustainable and/or cost-effective manner from bio-based starting materials containing only non-fossil fuel-based carbon, rather than solely through petrochemical-derived precursors. The evaluation of bio-based carbon in materials can be performed using standard test methods. The bio-based content of a material can be determined using radiocarbon and isotope ratio mass spectrometry. ASTM International (formerly the American Society for Testing and Materials) has established a standard test method for evaluating the bio-based content of materials. This ASTM method is designated as ASTM D6866. According to a preferred embodiment of the present invention, the proportion of carbon atoms contained in the compound of Formula (I) that exceeds 50% of the total number of carbon atoms contained in the compound of Formula (I) is bio-based. More preferably, based on the total number of carbon atoms contained in the compound of formula (I), a ratio exceeding 60%, 70%, 75%, 80%, 85%, or 90% of the carbon atoms contained in the compound of formula (I) is bio-based. The same applies to the compound of formula (II).

The present invention is further described with reference to the following examples. These examples are merely illustrative and do not limit the invention.

Example:

1. ingredient

1.1 lipophilic component

The lipophilic components tested included 2-methyl-5-cyclohexylpentanol, dimethylphenylbutanol, ethylhexylglycerin, caprylhydroxamic acid, fragrance 1 (product code: 482105) Citrus Fresh NX Perfume, and fragrance 2 (product code: 816918) Classico Power NX Perfume. Fragrances 1 and 2 are complex fragrance mixtures with low solubility in water.

1.2 3-hydroxypropyl ester

The following 3-hydroxypropyl esters were used in the experiment:

The compounds of formulas (I) and (II) can be obtained by following the synthetic approach described in, for example, 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 evaluation

2.1 Liquid lipophilic component

The sample was prepared as follows: the lipophilic component and the corresponding 3-hydroxypropyl ester were pre-mixed with glycol and a solubilizer. The mixture was heated to 60°C while stirring. Water was added and stirred for an additional 10 minutes. Turbidity was evaluated after 24 hours of preparation.

The samples were analyzed through visual evaluation and characterized using the following scales.

Turbidity was measured three times in Nephelometric Turbidity Units (NTU) using WTW’s TURB IR430.

2.2 Caprylhydroxamic acid (solid lipophilic component)

The sample was prepared according to the following procedure: Caprylhydroxamic acid and the corresponding 3-hydroxypropyl ester were pre-mixed with glycol and a solubilizer. The mixture was heated to 60°C while stirring. Water was added and stirred for an additional 10 minutes. After storing at room temperature (20 to 25°C) for 24 hours, the crystals were recovered by filtration. The filter paper and crystals were dried at 40°C for 24 hours.

3. result

3.1 2-methyl-5-cyclohexylpentanol

a) When used in combination with PEG-based solubilizers:

When the tested 3-hydroxypropyl ester was used, lower turbidity was observed in visual evaluation and instrumental measurements compared to the placebo (no 3-hydroxypropyl ester added). Accordingly, it was concluded that the solubility of 2-methyl-5-cyclohexylpentanol in aqueous solution can be improved by adding 3-hydroxypropyl ester.

b) When used in combination with PEG-free solubilizers:

3.2 Dimethyl phenylbutanol

When hydroxypropyl ester was used compared to a placebo, lower turbidity was observed in visual evaluation and instrumental measurements. The solubility of dimethyl phenylbutanol in an aqueous solution can be improved by adding the ester.

3.3 Ethylhexylglycerin

When hydroxypropyl ester was used compared to a placebo, lower turbidity was observed in visual evaluation and instrumental measurements. The solubility of dimethyl ethylhexylglycerin in an aqueous solution can be improved by adding the ester.

3.4 Caprylhydroxamic acid

The addition of propanediol caprylate reduces the recrystallization of caprylylhydroxamic acid compared to a placebo.

3.5 Fragrance 1: Citrus Fresh NX Perfume

3.6 Fragrance 2: Classico Power NX Perfume

4. Formulation Examples

In the following examples, the content of all formulations is expressed in weight percent.

4.1 Deodorization (DEO)

4.1.1 ACH-containing deodorant spray

4.1.2 Cool Relief Deo Plus

4.1.3 Sports Fit Deo

4.1.4 Deodorant Stick

4.1.5 Sweat suppressant stick

4.1.6 Roll-on gel type deodorant formulation

4.1.7 Clear Deo Antiperspirant Roll-on

4.2 Gel

4.2.1 Aftershave Tonic

4.2.2 Cool & Hot Firming Gel (Contains Thermolat & Frescolat)

4.2.3 Frosty Facial Foam

4.2.4 Moisture Face Gel (Water Clear Type)

4.2.5 Intimate Sensi Gel

4.2.6 Mild Feminine Wash

4.2.7 Biotic Acne Care Gel

4.2.8 Anti-wrinkle gel

4.2.9 Cleansing Micellar Gel

4.2.10 Spray-type Anti-Cellulite Gel

4.3 Wet wipes

4.3.1 PEG-Free Wet Wipes

4.3.2 Intimate Tissue

4.4 Oral Care

4.4.1 Protective Mouth Rinse

4.4.2 Alcohol-free mouthwash (ready-to-use type)

4.4.3 Mouthwash concentrate

4.4.4 Breath Freshener Mouth Spray

4.5 Masks

4.5.1 Sheet Mask - New Skin

4.5.2 Sheet Mask - Ultra Calming

4.5.3 Watermelon Face Mask & Scrub

4.6 Home Care

4.6.1 Glossy Floor Cleaner

4.6.2 Simple Floor Cleaner

Claims (15)

As a solubilizing agent or auxiliary solubilizing agent for lipophilic substances in a water-based preparation, at least one of the compounds of the following formula (I) is used.

Here, R is a use selected from the group consisting of:
,
,
,
,
and
. A method for improving the solubility of a lipophilic substance in an aqueous formulation, comprising or consisting of the following:
(a) providing at least one of the compounds of formula (I) described in claim 1;
(b) providing at least one lipophilic substance;
(c) providing an aqueous base preparation; and
(d) adding at least one compound of (a) to at least one lipophilic substance of (b) and the base preparation of (c) in an amount effective for increasing the solubility of the lipophilic substance in the aqueous preparation. Aqueous preparations containing the following:
(i) at least one of the compounds of formula (I) described in claim 1;
(ii) lipophilic substances; and
(iii) Water. In claim 3, the lipophilic substance is 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 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, A preparation characterized by being selected from the group consisting of ubiquinone-10, climbazole, aldehyde C12, lilial, dihydromyrcenol, globalide, linalyl acetate, citronelly acetate, phenylethyl methyl ether, and a mixture of two or more lipophilic substances. A preparation according to paragraph 3 or 4, further comprising a PEG-based solubilizer or a PEG-free solubilizer. In claim 5, the PEG-based solubilizer or PEG-free solubilizer is PEG-40 Hydrogenated Castor Oil, Polysorbate 20, Polysorbate 60 and Polysorbate 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 (PPG-1-PEG-9 Lauryl Glycol Ether), Polyglyceryl-2 Caprate, Isoceteth-20, PPG-13-decyltetradeceth-24, Sodium Cocoyl Glutamate, Sucrose Trilaurate, Sorbitan Sesquicaprylate, Lauroyl Alanine, Heptyl Glucoside, Capryloyl/Caproyl Methyl Glucamide, Polyoxyethylene sorbitan monolaurate, Polyoxyethylene lauryl ether A preparation characterized by being selected from the group consisting of ether), PEG-400 monolaurate, sodium xylene sulfonate, sodium cumene sulfonate, and a mixture of two or more of the above solubilizing agents. A preparation according to claim 6, characterized in that the PEG-based solubilizer comprises or consists of PEG-40 hydrogenated castor oil and/or Trideceth-9. A preparation according to claim 6, characterized in that the PEG-free solubilizing agent comprises polyglyceryl-4 caprylate or is composed of polyglyceryl-4 caprylate. A preparation comprising a hydrophilic solvent in addition to any one of paragraphs 3 through 8. A preparation according to claim 9, wherein the hydrophilic solvent is selected from the group consisting of glycerin, propylene glycol, butylene glycol, isopropyl alcohol, propanediol, dipropylene glycol, propylene carbonate, ethanol, hexylene glycol, glycerin carbonate, methylpropanediol, butylene carbonate, dimethyl isosorbide, or a mixture of two or more of the hydrophilic solvents. In any one of paragraphs 3 through 10, the above-mentioned preparation is a preparation satisfying one or more of the following:
A preparation composed mainly of water, preferably wherein the preparation is an aqueous preparation, an aqueous/alcoholic preparation, or an aqueous/glycolic preparation;
A transparent or translucent preparation;
Personal care formulations and household formulations, preferably formulations selected from the group consisting of creams, lotions, sticks, gels, solutions, wipes, masks, deodorants, shampoos, conditioners, sunscreens, micellar waters, dishwashing liquids, multi-purpose cleaners, liquid soaps, mouthwashes, and oral sprays. A preparation according to any one of claims 3 to 11, comprising at least one compound of formula (I) in an amount of 0.01 to 10 weight% based on the total weight of the preparation, preferably 0.05 to 2.5 weight%, and more preferably 0.1 to 1.0 weight%. In any one of claims 3 to 12, the preparation comprises water and at least one compound of formula (I) 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;
and/or
A preparation comprising at least one compound of formula (I) and 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, and most preferably 1:10 to 1:1. In the use according to paragraph 1 or the method according to paragraph 2, the use as a solubilizing agent or the increase in solubility entails reducing the turbidity of the above-mentioned preparation. In the use according to paragraph 1 or 14 or the method according to paragraph 2 or 14, the said preparation is a preparation as described in any one of paragraphs 3 through 11.