Bio-based glycerol heptaester compositions, their preparation methods and applications

Abstract

This invention relates to bio-based glyceryl heptaester compositions, preferably glyceryl monoheptaester compositions, their preparation methods, and their applications, including the use of the compositions of the invention in formulations for cosmetic and other personal care applications. The bio-based monoglyceryl monoester (MGME) compositions comprise a mixture containing one or more compounds of formula (I), wherein R1, R2, and R3 are independently -H or -C(O)-C6 alkyl groups. The composition contains greater than about 60 wt% and less than about 98 wt% of glyceryl monoheptaester. The carbon present in the one or more compounds of formula (I) is bio-based. When tested according to the EpiDerm skin irritation test (OECD 439) with a 1% aqueous solution of the composition, the ET of the composition is... 50 The value is greater than 24 hours. This invention also relates to microbial inhibitory concentrates (MBCs) comprising the disclosed compositions.

Description

[0001] Cross-reference to related applications

[0002] This application claims priority to U.S. Provisional Application No. 63 / 109,657, filed November 4, 2020, which is incorporated herein by reference. Technical Field

[0003] This invention relates to bio-based glyceryl heptaester compositions, methods for their preparation, and applications thereof, including the use of the compositions in cosmetic and other personal care formulations. Background Technology

[0004] Monoglyceryl monoesters (MGMEs), also known as monoglycerides, are compounds widely used in the cosmetic, pharmaceutical, and food industries due to their non-toxic, non-ionic, amphiphilic nature. (See, for example, Kabara, JJ Chemistry and Biology of Monoglycerides in Cosmetic Formulations, Ch. 12 in Glycerine: A Key Cosmetic Ingredient, Jungermann, E. and Sonntag, NOV, eds.; Marcel Dekker, Inc.: New York, 1991, pp 311-344; see also Johnson, Jr.W.Int.J.Tox., 2004, 23(Suppl.2), 55–94.). MGMEs have been reported as surfactants, emulsifiers, emollients, skin conditioners, and deodorants in cosmetic and personal care formulations.

[0005] Of particular interest and practical application are MGMEs with acyl chains containing eight to fourteen carbon atoms. Such MGMEs are typically viscous fluids at room temperature or soft solids with low melting temperatures. Due to their amphiphilic nature, these MGMEs can be dispersed in aqueous media, where they exhibit surface activity and self-assembly at interfaces. These amphiphilic molecules are also well-suited for interaction with amphiphilic molecules, including those forming lipid bilayers (e.g., those that form microbial cell membranes). Thus, C8-C... 14MGMEs have the ability to increase cell membrane permeability and thus are used as effective microbiostatic agents, disrupting cellular homeostasis and inhibiting microbial growth. (See, e.g., Kabara, J. Fatty Acids and Esters as Multifunctional Components, Ch. 5 in Preservative-Free and Self-Preserving Cosmetics and Drugs: Principles and Practice, Kabara and Orth, eds., Marcel Dekker, Inc.: New York, 1997, 119-138). The most common MGMEs used for this purpose are those with even-numbered, straight-chain C8to C 14 acyl chains (i.e., octanoyl, hexanoyl, lauroyl, or myristoyl) with omega-unsaturated C 11 chains (i.e., 10-undecylenoyl), or mixtures thereof.

[0006] C8to C 14 The same properties that make MGMEs effective surfactants, emulsifiers, and microbiostatic agents also make them effective skin permeation enhancers, as they can interact with and partially fluidize the stratum corneum skin barrier lipid bilayers, making the lipid bilayers more permeable to topically applied compounds. Thus, C8to C 14 MGMEs have been widely used as skin permeation enhancers for the transdermal delivery of pharmaceutically active ingredients. However, due to the permeation ability of the MGMEs themselves or unintended permeation enhancement of other topically applied ingredients such as fragrances, sunscreens, preservatives, etc., C8to C 14 The ability of MGMEs to modulate skin barrier permeability can also result in skin irritation. Thus, there is a need to develop MGME compositions that retain the functional utility of C8to C 14 MGMEs while simultaneously reducing the undesirable side effects (e.g., irritation) of MGMEs.

[0007] C8to C 14 Another desirable aspect of MGMEs relates to their sustainability, which makes them particularly useful for formulating environmentally reduced impact products. In addition to being non-toxic and generally recognized as safe (GRAS) compounds, these ingredients are also considered highly sustainable because they are readily biodegradable and can be derived from renewable, plant-based feedstocks (i.e., C8to C 14Fatty acids and glycerol) synthesis. These fatty acids and glycerol can be derived from any plant-derived triglyceride oil, with coconut oil and palm kernel oil being the most common sources due to their high content of these acyl chain lengths. However, recent controversies regarding the negative environmental and social impacts of oil palm cultivation and palm / palm kernel oil production have made this source of fatty acids and glycerol less desirable from a commercial perspective, and the market continues to demand ingredients based on alternative sources to these plant-derived feedstocks.

[0008] The typical (trans)esterification process involving reaction of glycerol with fatty acids or fatty acid esters to produce MGME results in an equilibrium distribution of glycerol (“free glycerin”) and monoacyl, diacyl, and triacyl esters of glycerol (see, e.g., Kabara). For example, when one mole of glycerol is reacted with one mole equivalent of fatty acid with the goal that the average glycerol esterification degree of the monoester is 1.0, the resulting equilibrium mixture will contain about 40-50 mol% monoester, 20-30 mol% diester, 0-10 mol% triester, and 20-30% free glycerol (see Feuge, R.O. and Bailey, A.E. Modification of Vegetable Oils, VI. The Practical Preparation of Mono- and Diglycerides, Oil & Soap, 1946, 23(8), 259-264). MGME products comprising >80% monoester are typically obtained by fractionation of the initial equilibrium reaction product mixture to remove free glycerol, diester, and triester to provide a higher concentration of monoester product. This fractionation is typically achieved by an energy-intensive process of molecular or short-path distillation to separate the components. Other separation methods, such as extraction (“scrubbing”) to remove free glycerol prior to distillation, followed by fractionation to separate the monoester fraction from the heavier diester and triester components, can also be employed.

[0009] What is needed are MGME compositions prepared from sustainable feedstocks and improved methods of their preparation and purification. SUMMARY

[0010] The present invention relates to a bio-based monoglyceride (MGME) composition comprising a mixture comprising one or more compounds of formula (I):

[0011]

[0012] wherein R1, R2, and R3 are independently -H or -C(O)-C6 alkyl (e.g., n-heptanoyl), wherein the composition comprises greater than about 60 wt% and less than about 98 wt% glycerol monoheptanoate, and wherein the carbon present in the one or more compounds of Formula (I) is biobased.

[0013] The composition of the preceding paragraph, wherein the composition comprises glycerol diheptanoate, glycerol triheptanoate, or a combination thereof, at a concentration of about 2 wt% to about 40 wt%.

[0014] The composition of any of the preceding paragraphs (alone or in combination), wherein the composition comprises less than about 30% glycerol.

[0015] The composition of any of the preceding paragraphs (alone or in combination), wherein the average glyceryl esterification degree of the composition is about 0.7 to about 1.4.

[0016] The composition of any of the preceding paragraphs (alone or in combination), wherein at least 95% of the -C(O)-C6 alkyl present in the composition is n-heptanoyl.

[0017] The composition of any of the preceding paragraphs (alone or in combination), wherein the ET 50 value of the composition is greater than 24 hours when tested according to the EpiDerm Skin Irritation Test (OECD 439) as a 1% aqueous solution of the composition.

[0018] The composition of any of the preceding paragraphs (alone or in combination), wherein the MTT cell viability value of the composition at about 24 hours is greater than 50% when tested according to the EpiDerm Skin Irritation Test (OECD 439) as a 1% aqueous solution of the composition.

[0019] The composition of any of the preceding paragraphs (alone or in combination), further comprising an enhancer selected from the group consisting of: one or more polyols, one or more glycerol ethers, one or more chelating agents, and combinations thereof.

[0020] A formulation comprising the composition of any of the preceding paragraphs (alone or in combination), wherein the shelf life of the formulation against microbial contamination is at least 12 months, or at least 18 months, or at least 24 months.

[0021] A formulation comprising the composition of any of the preceding paragraphs (alone or in combination), wherein the formulation has the same or superior shelf life against microbial contamination due to the presence of the C7 biobased monoglyceride described herein in the formulation as compared to a formulation containing the same weight concentration of C8 to C 14 The formulation has the same or superior shelf life against microbial contamination as compared to a reference formulation of the MGME composition.

[0022] A formulation comprising the composition of any of the preceding paragraphs (alone or in combination), wherein the formulation has a turbidity value of less than about 100 NTU.

[0023] The formulation of any of the preceding paragraphs (alone or in combination), further comprising at least one ingredient selected from the group consisting of: water; surfactants, including anionic, cationic, nonionic, and zwitterionic surfactants; emulsifiers; emollients; humectants; conditioning agents for hair, skin, or nails; chelating agents; active agents; bleaching or whitening agents; additional pH adjusting agents; fragrances; colorants; exfoliants; antioxidants; botanicals; botanical extracts; mica; montmorillonite; thickening agents; rheology modifiers; oils; dyes; waxes; amino acids; nucleic acids; vitamins; hydrolyzed proteins and derivatives thereof; glycerin and derivatives thereof; enzymes; antiinflammatories and other medicaments; microbiocides; antifungals; bacteriocides; antioxidants; UV absorbers; dyes and pigments; preservatives; sunscreen actives; antiperspirant actives; oxidizing agents; pH balancing agents; moisturizers; peptides and derivatives thereof; anti-aging actives; hair growth promoters; anti-cellulite actives; and combinations thereof.

[0024] A method of preserving a formulation against microbial contamination, the method comprising adding a sufficient amount of the composition of any of the preceding paragraphs (alone or in combination).

[0025] A microbial barrier concentrate (MBC) comprising the bio-based monoglyceride composition of any of the preceding paragraphs (alone or in combination), and at least one of glycerin and a C3-C4 diol.

[0026] The microbial barrier concentrate of any of the preceding paragraphs (alone or in combination), wherein the microbial barrier concentrate comprises the bio-based monoglyceride composition in an amount of about 30 wt% to about 85 wt%.

[0027] The microbial barrier concentrate of any of the preceding paragraphs (alone or in combination), wherein the microbial barrier concentrate comprises glycerin, a C3-C4 diol, or a combination thereof in an amount of about 1 wt% to about 70 wt%.

[0028] The composition, formulation, or microbial barrier concentrate of any of the preceding paragraphs (alone or in combination), further comprising one or more polyols selected from the group consisting of: glycerin, propylene glycol, 1,2-propanediol, 1,2-butanediol, 1,3-butanediol, 1,4-butanediol, 2,3-butanediol, 1,2-hexanediol, 1,2-heptanediol, 2,3-octanediol, octylene glycol, decylene glycol, sorbitol, sorbitan, and combinations thereof.

[0029] The composition, formulation, or microbial inhibitory concentrate of any of the preceding paragraphs (alone or in combination) further comprises one or more glyceryl ethers selected from the group consisting of hexyl glycerol, cyclohexyl glycerol, heptyl glycerol, octyl glyceryl ether, methyl heptyl glycerol, ethyl hexyl glycerol, and combinations thereof.

[0030] The composition, formulation, or microbial inhibitory concentrate of any of the preceding paragraphs (alone or in combination) further comprises one or more chelating agents selected from the group consisting of heptyl hydroxamic acid and salts thereof, octyl hydroxamic acid (octanoyl hydroxamic acid) and salts thereof, pelargonic acid hydroxamic acid and salts thereof, citric acid and salts thereof, hexacarbonyl hydroxamic acid and salts thereof, glutamic acid diacetic acid tetrasodium, phytic acid and salts thereof, gluconic acid and salts thereof, galacturonic acid and salts thereof, and galactaric acid and salts thereof, and combinations thereof.

[0031] The present invention provides sustainable, plant-based MGME compositions that overcome the irritation issues associated with C8 to C 14 MGME without sacrificing performance, most notably microbial inhibitory efficacy for preserving formulated products.

[0032] Surprisingly, selection of odd-chain C7 acyl groups significantly reduces the cytotoxicity and irritation of MGME while maintaining microbial inhibitory efficacy. Additionally, it has been discovered that retaining some or all of the diester and triester components in the MGME composition further reduces the cytotoxicity and irritation of the C7 MGME composition without reducing microbial inhibitory efficacy. It has also been discovered that the C7 MGME compositions of the present invention improve the clarity and translucency of clear formulations compared to formulations prepared with traditional C8 to C 14 MGME.

[0033] To ensure the sustainable benefits of the C7 MGME compositions, the C7 acid (n-heptanoic acid) must be derived from plant-based feedstocks, i.e., it must be bio-based n-heptanoic acid or “bio-heptanoic acid.” Bio-heptanoic acid is derived from the thermal cleavage of ricinoleic acid, an unsaturated C 18 hydroxy fatty acid derived from the saponification of castor oil obtained from the seeds of the castor plant (Ricinus communis). Thermal cleavage of ricinoleic acid or its corresponding methyl ester (methyl ricinoleate) produces heptanal and undecylenic acid or methyl undecylenate. Bio-heptanal is readily converted to bio-heptanoic acid via catalytic oxidation, the resulting bio-heptanoic acid having >99% purity of linear, saturated C7 acid (commercially available, for example, from Arkema under the trade name Bio-Heptanoic Acid).

[0034] The use of bio-heptanoic acid is particularly important because bio-heptanoic acid does not contain branched C7 acids or unsaturated impurities. For example, n-heptanoic acid obtained from petrochemical feedstocks via the oxo process can contain up to 3.5 wt% 2-methylhexanoic acid (Oxea’s n-heptanoic acid sales specification). Branched and / or unsaturated alkanic acid impurities are undesirable constituents because when prepared using petroleum-chemical based heptanoic acid, residual unreacted branched and / or unsaturated fatty acids can impart undesirable odors to the resulting C7 MGME composition.

[0035] BRIEF DESCRIPTION OF DRAWINGS

[0036] Figure 1 EpiDerm TM Graphical representation of cell viability data as a function of exposure time. DETAILED DESCRIPTION

[0037] Before the present compounds, compositions, and methods are described, it is to be understood that the application described and claimed herein is not limited to the specific methods, compositions, or methods described, as such may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular versions or embodiments only and is not intended to limit the scope of the present application which will be limited only by the appended claims. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. Any methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the present application, although the preferred methods, devices, and materials are now described. All patents, patent applications, and other publications referred to herein or otherwise mentioned in connection with this application are incorporated herein by reference in their entirety. Nothing herein is to be construed as an admission that the application is not entitled to antedate such publication by virtue of prior invention. The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present application is not entitled to antedate such publication by virtue of prior invention.

[0038] As used herein and in the appended claims, the use of “a,” “an,” and / or “the” is intended to include both singular and plural, unless the context clearly indicates otherwise. Thus, for example, reference to “a cell” refers to one or more cells known to one of skill in the art, and equivalents thereof, and the like.

[0039] Unless otherwise indicated, “%” can refer to percent by weight, or percent by volume, or percent by weight per unit volume, and the relevant units will be apparent to one of ordinary skill in the art on the basis of context.

[0040] "cosmetically acceptable" means suitable for use in contact with the skin, preferably human skin, without undue toxicity, incompatibility, instability, irritation, allergic response, and the like.

[0041] Where applicable, chemical substances are identified by their INCI name according to the International Nomenclature of Cosmetic Ingredients guidelines. Additional information, including suppliers and trade names, can be found under the appropriate INCI monograph in the International Cosmetic Ingredient Dictionary and Handbook, 16th edition, published by the Personal Care Products Council (Washington, D.C.), or can be found in the Personal Care Products Council Online Information Database (http: / / online.personalcarecouncil.org).

[0042] In many embodiments, the present application includes bio-based C7 MGME compositions. In producing bio-based MGME compositions, it is necessary to use bio-based or "natural" feedstocks. One example of a bio-based MGME composition is one that is made from feedstocks of biological origin (e.g., feedstocks from current and sustainable agricultural activities, such as fermentation, algal, plant or vegetable sources; e.g., derived from vegetable sources, preferably using non-genetically modified organisms or biomass, and not petroleum chemical sources (e.g., from 21st century sustainable tree and plant cultivation activities as opposed to fossil sources such as petroleum, natural gas or coal). Such feedstocks are referred to herein as "natural" and "renewable" (i.e., "sustainable"), and are referred to in the art as non-petroleum sourced feedstocks. Furthermore, such materials are formed from "new" carbon, as opposed to petroleum or other fossil fuel sources ("old" carbon). Such products are referred to herein as "natural" products, and are referred to in the art as non-petroleum chemical sourced products or "bio" products. As used herein, the term "sustainable" refers to starting materials, reaction products, compositions and / or formulations derived from renewable sources. Thus, the term "sustainable" is distinguished from "non-sustainable" starting materials, reaction products, compositions and / or formulations that contain carbon from finite natural resources (e.g., fossil fuels (e.g., petroleum or coal), natural gas, etc.). Thus, natural or bio products are not petroleum chemical sourced and / or are made from sustainable and renewable resources, as opposed to petroleum chemical sources. True natural products (biological compounds) are formed using biomass (e.g., materials stored by carbon cycling processes in living plants, roots, etc., or materials released by animal respiration or waste, or materials released by decomposition). Fossil fuels (a source of petroleum chemical sourced carbon) are created when carbon is degraded and broken down under pressure over millions of years. Biological compounds herein are intended to include materials derived from carbon of recently existing and / or sustainable plant sources / biomass, and expressly exclude materials derived from fossil fuels.

[0043] The compositions of the present application can be identified by their bio-based carbon content, and distinguished from prior art compositions. In some embodiments, the bio-based carbon content can be measured by radiocarbon dating to determine the relative age of a material composed of organic (i.e., carbon-containing) matter. Radiocarbon is an unstable isotope of carbon, known as carbon-14 (i.e., "14C"). 14 C"). 14 C is an unstable isotope that emits radiation energy in the form of beta particles at a very constant rate (i.e., the half-life of radiocarbon is 5730 years), and eventually decays to the more stable nitrogen-14 (i.e., "14N). Since petroleum-based (i.e., petroleum chemical sourced) feedstocks are derived from plants and animals buried millions of years ago, the radiocarbon (i.e., 14C) of such feedstocks is essentially zero (i.e., the 14C has decayed to 14N). Thus, the 14C of a material is a measure of the age of the material, and can be used to distinguish between petroleum chemical sourced and bio-based materials. 14 N). Since petroleum-based (i.e., petroleum chemical sourced) feedstocks are derived from plants and animals buried millions of years ago, the radiocarbon (i.e., 14C) of such feedstocks is essentially zero (i.e., the 14C has decayed to 14N). Thus, the 14C of a material is a measure of the age of the material, and can be used to distinguish between petroleum chemical sourced and bio-based materials.14 C) has been lost to radioactive decay. ASTM International standards provide a test standard for determining the authenticity of "bio-based compounds" using radiocarbon, which can be found in ASTM D6866-16. This standard distinguishes newer carbon from carbon derived from fossil fuels, or petroleum and petrochemical sources (i.e., "old carbon"). The amount of 14 C is known, and thus the percentage of carbon from renewable sources can be estimated from total organic carbon analysis, which provides the necessary data to determine whether a compound is truly derived from "natural" and / or "sustainable" ("renewable") feedstock sources, or conversely, derived from "old" sequestered compounds (i.e., petrochemical or petroleum-based sources). The use of petroleum-based (also referred to as "fossil-based") feedstocks is generally considered to be unsustainable, i.e., old carbon is not a sustainable and renewable feedstock, and is not considered to be "natural" and / or "sustainable" in the art.

[0044] In some embodiments, the compositions of the present application comprise bio-based carbon as substantially all of the carbon present in the mixture of compounds, which can refer to a bio-based carbon content of at least 90%, at least 95%, or at least 98%. In some embodiments, the compositions of the present application comprise fully bio-based MGME and fully bio-based reactants having a measured bio-based carbon content of at least about 98%, at least about 99%, at least about 99.5%, or about 100%.

[0045] In some embodiments, the compositions of the present application comprise a bio-based carbon content substantially equal to the 14 C content of the current atmosphere, as determined according to ASTM D6866. In some embodiments, the compositions of the present application comprise a bio-based carbon content of at least about 90%, at least about 95%, at least about 98%, or at least about 99% of the 14 C content of the current atmosphere, as determined according to ASTM D6866. In some embodiments, the compositions of the present application comprise at least about 0.8 14 C atoms per 10 14 C atoms per 10 14 C atoms per 10 12 C atoms per 10 14 C atoms per 10 12 C atoms per 10 14 C atoms per 10 12 C atoms per 10

[0046] A newer method for identifying bio-based feedstocks utilizes mass spectrometry to analyze stable isotopes in detail and assess carbon-12 / carbon-13 and / or hydrogen-1 / hydrogen-2 ratios. This test is available through several analytical service testing organizations and is faster, more cost effective, and produces more detailed information than the radiocarbon testing method. Stable isotope analysis is based on the principle of kinetic isotope effects. Kinetic isotope effects are well known to those skilled in the art of chemical kinetics. In the broadest terms, heavy isotopes of a particular element react more slowly than their lighter counterparts (e.g., carbon-12 vs. carbon-13). Thus, when plants incorporate carbon dioxide into their biomass, the ratio of carbon-12 to carbon-13 will vary depending on the type of chemistry the plant is using to make the biomass (e.g., is the plant following the C3 photosynthetic pathway or the C4 photosynthetic pathway). This is commonly reported as the delta 13 C / 12 C ratio (i.e., delta 13 C) and referenced to a current carbon dioxide standard. In addition, similar isotope kinetic effects are observed when water is incorporated into new biomass and this is measured as the delta 2 H / 1 H ratio (i.e., delta 2 H). Using the delta 13 C ratio in conjunction with the delta 2 H ratio, one skilled in the relevant art is able to readily distinguish and verify the nature of the feedstock used to make the product being analyzed (i.e., is it a petrochemical source or derived from a recently living or living algal, plant, or similar biological source).

[0047] A bio-based monoglyceride composition. The bio-based monoglyceride (MGME) composition comprises a compound of Formula (I):

[0048]

[0049] wherein R1, R2, and R3 are independently -H or -C(O)-C6 alkyl (e.g., n-heptanoyl), can be prepared, for example, by reaction of bio-based glycerol with bio-based n-heptanoic acid (bio-heptanoic acid).

[0050] In some embodiments, the C7 MGME compositions of the present application can be synthesized according to any method known to those skilled in the art of glyceride synthesis (see, e.g., DE 102008013023 Al, which describes the synthesis of glyceryl octanoate). A preferred route to the C7 MGME compositions of the present application is the direct esterification of bio-based glycerol with bio-based heptanoic acid, wherein water, which is a condensation byproduct, is removed to drive the esterification reaction to completion. Bio-heptanoic acid is a limiting reagent in the synthesis, as maintaining a molar ratio of bio-heptanoic acid to glycerol less than or equal to one (<1) favors the formation of mono-ester products and limits the formation of di-ester and tri-ester co-products in the resulting mixture. The ratio of bio-heptanoic acid to glycerol is preferably from about 0.4 to about 1.0, more preferably from about 0.4 to about 0.6. In some embodiments, the ratio of bio-heptanoic acid to glycerol is about 0.5.

[0051] The reaction is carried out by charging the glycerol and bio-heptanoic acid into a reaction vessel and heating under an inert atmosphere, such as nitrogen, while providing sufficient agitation to ensure adequate mixing of the reactants. The reaction is carried out at a temperature of from about 75 °C to about 300 °C, preferably from about 150 °C to about 250 °C, most preferably from about 175 °C to about 225 °C. When the desired reaction temperature is reached, the reaction can be carried out at atmospheric pressure with an inert gas charged or under vacuum to drive the conversion to esters by removing the condensation byproduct, i.e., water. If desired, an esterification catalyst can be used to improve the reaction kinetics and reduce the reaction time. Examples of such catalysts include acid catalysts, such as methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, and the like, and transition metal catalysts, such as tetra-n-butyl titanate, stannous octoate, and the like. In preferred embodiments, the reaction is carried out without a catalyst.

[0052] In some embodiments, the C1-C4 esters of bio-heptanoic acid, such as methyl heptanoate or ethyl heptanoate, can be used as starting materials. In such embodiments, the reaction is carried out as an ester exchange between the heptanoate ester and bio-based glycerol, while removing the C1-C4 alcohol, such as methanol or ethanol, as a condensation byproduct to drive the reaction to completion. Another ester exchange route to the C7 MGME compositions of the present application is the ester exchange of bio-based glycerol diheptanate and / or glycerol triheptanate (i.e., a glyceride composition having an average esterification degree > 2.0) with bio-based glycerol to reduce the average glyceryl esterification degree to less than 1.5, preferably from about 0.7 to about 1.4. For example, bio-based glycerol triheptanate (e.g., triheptanoin) can be ester exchanged with bio-based glycerol to produce a distribution comprising mono-ester, di-ester, and tri-ester byproducts, as well as free glycerol.

[0053] The crude reaction product of the condensation of bioheptanoic acid (or simple esters thereof) with bio-based glycerol will comprise a mixture of free glycerol, glycerol monoheptanoate, glycerol diheptanoate, and glycerol triheptanoate. The crude reaction product can be further refined to obtain the C7 MGME composition of the present application using any glycerol ester purification method known to those skilled in the art. For example, the crude reaction product can be stripped under vacuum to remove unreacted bioheptanoic acid or volatile byproducts that can impart undesirable odors to the composition. The crude reaction product can also be extracted, i.e., washed, with a solvent to remove certain fractions of the reaction product. For example, the C7 MGME composition can be extracted with water to remove unreacted glycerol. In some embodiments, an ionic salt, such as sodium chloride, potassium chloride, calcium chloride, and the like, can be added to the water extraction phase to facilitate phase separation of the glycerol-rich aqueous layer and the ester-rich organic layer. The extraction and separation processes can be enhanced by heating, mixing, centrifugation, and the like. After the ester-rich organic layer is separated from the glycerol-rich aqueous phase, the organic layer can be dried by applying heat, vacuum, and / or inert gas sparging to remove any residual water.

[0054] The C7 MGME composition of the present application can be further fractionated to increase the monoester content of the composition. Techniques such as molecular distillation (e.g., short path distillation, wiped film distillation, and the like) can be used to remove unreacted glycerol and separate the monoester from the heavier diester and triester byproducts. The C7 MGME composition can also be treated with a processing aid (e.g., activated carbon, diatomaceous earth, and the like) and filtered to refine the composition and improve properties such as color and odor.

[0055] Another glycerol ester route that can be used to synthesize the C7 MGME composition of the present application is the reaction of bioheptanoic acid with glycidol derived from bio-based glycerol. In this reaction, the nucleophilic challenge of the epoxide ring of glycidol leads to ring opening, resulting in the production of 2,3-dihydroxypropyl heptanoate, i.e., glycerol monoheptanoate, in very high yield, with low yields of diester and triester byproducts, respectively.

[0056] The bio-based C7 MGME composition comprises about 60 wt% to about 98 wt% glycerol monoheptanoate, e.g., 65 wt% to 95 wt%, 65 wt% to 85 wt%, or 65 wt% to 75 wt%. In terms of the upper limit, the amount of glycerol monoheptanoate can be less than 98 wt%, e.g., less than 95 wt%, less than 85 wt%, or less than 75 wt%. In terms of the lower limit, the amount of glycerol monoheptanoate can be greater than 60 wt%, e.g., greater than 65 wt%.

[0057] In some embodiments, the present compositions comprise a controlled amount of glycerol diheptanoate and / or glycerol triheptanoate. The bio-based C7 MGME compositions comprise about 1 wt% to about 40 wt% glycerol diheptanoate, such as 1 wt% to 30 wt%, 2 wt% to 30 wt%, 2.5 wt% to 30 wt%, or 5 wt% to 25 wt%. In terms of upper limits, the amount of glycerol diheptanoate can be less than 40 wt%, such as less than 35 wt%, less than 30 wt%, or less than 25 wt%. In terms of lower limits, the amount of glycerol diheptanoate can be greater than 1 wt%, such as greater than 2 wt%, greater than 2.5 wt%, or greater than 5 wt%.

[0058] The bio-based C7 MGME compositions comprise about 0 wt% to about 10 wt% glycerol triheptanoate, such as 0 wt% to 6 wt%, 0 wt% to 4 wt%, or 1 wt% to 4 wt%. In terms of upper limits, the amount of glycerol triheptanoate can be less than 10 wt%, such as less than 6 wt%, less than 4 wt%, or less than 2 wt%. In terms of lower limits, the amount of glycerol triheptanoate can be greater than 0 wt%, such as greater than 1 wt%.

[0059] The bio-based C7 MGME compositions comprise a total combined amount of glycerol diheptanoate and glycerol triheptanoate of about 2 wt% to about 40 wt%, such as 2 wt% to 35 wt%, 2 wt% to 30 wt%, or 2 wt% to 25 wt%. In terms of upper limits, the total combined amount of glycerol diheptanoate and glycerol triheptanoate can be less than 40 wt%, such as less than 35 wt%, less than 30 wt%, or less than 25 wt%. In terms of lower limits, the total combined amount of glycerol diheptanoate and glycerol triheptanoate can be greater than 2 wt%, such as greater than 3 wt%, greater than 4 wt%, or greater than 5 wt%.

[0060] The bio-based C7 MGME compositions comprise about 0 wt% to about 30 wt% glycerol, such as 1 wt% to 30 wt%, 2 wt% to 20 wt%, 2 wt% to 15 wt%, or 2 wt% to 10 wt%. In terms of upper limits, the amount of glycerol can be less than 30 wt%, such as less than 20 wt%, less than 15 wt%, or less than 10 wt%. In terms of lower limits, the amount of glycerol can be greater than 0 wt%, such as greater than 1 wt%, or greater than 2 wt%. In some embodiments, the present compositions are substantially free of glycerol (i.e., the compositions contain less than about 2 wt%, preferably less than about 1 wt%, or most preferably less than 0.5 wt% glycerol).

[0061] The degree of esterification (DE) of the MGME composition can be referred to by those skilled in the relevant art as the average glyceryl DE, where the average glyceryl DE is the ratio of the number of glyceryl ester groups in the composition to the sum of the number of glyceryl ester groups plus the number of unesterified hydroxyl groups, calculated three times, i.e., the total number of hydroxyl groups on a glycerol molecule that are available for esterification. Thus, the DE of unesterified glycerol is 0, and the DE of a glyceryl triester (triglyceride) is 3. The average glycerol DE can also be calculated based on a weighted average of glycerol, monoglyceride, diglyceride, and triglyceride present in the MGME composition. The compositions of the present invention can be adjusted to have a desired average glyceryl DE suitable for any particular formulation or application. In some embodiments, the average glyceryl esterification degree of the compositions of the present invention is from about 0.7 to about 1.4, from about 0.8 to about 1.4, from about 0.9 to about 1.4, from about 1.0 to about 1.4, from about 0.9 to about 1.3, or from about 1.0 to about 1.3. In terms of upper limits, the average glyceryl esterification degree can be less than 1.4, e.g., less than 1.3, less than 1.2, or less than 1.1. In terms of lower limits, the average glyceryl esterification degree can be greater than 0.7, e.g., greater than 0.8, greater than 0.9, or greater than 1.0.

[0062] In some embodiments, the alkyl moieties of the glyceride acyl side chains R1, R2, and R3 present in the compositions of the present invention are preferably linear. In some embodiments, the alkyl moieties of the glyceride acyl side chains R1, R2, and R3 present in the compositions of the present invention are at least 95% linear, at least 98% linear, or at least 99% linear. In some embodiments, the glyceride side chains present in the compositions of the present invention are substantially free of branched R1, R2, or R3 groups.

[0063] The compositions of the present invention have superior optical, odor, and skin sensitivity properties compared to other compositions, particularly other glyceride compositions.

[0064] Formulations. The compositions of the present application can be incorporated into a number of consumer and industrial end-use formulations, such as those used for personal care, home and institutional care, pharmaceutical, veterinary care, oral care, fabric care, metal working, food processing, and industrial applications. In one embodiment of the present application, the bio-based C7 MGME composition or a composition comprising the bio-based C7 MGME composition is incorporated into a formulation such as a personal care formulation. Embodiments include incorporation into a formulation with at least one other ingredient. Suitable formulation and additive ingredients known to those skilled in the art are described in the International Cosmetic Ingredient Dictionary and Handbook, 16th edition, published by the Personal Care Products Council, Washington, D.C., or in the Personal Care Products Council Online Information Database ((http: / / online.personalcarecouncil.org). Formulations and ingredients can include, but are not limited to: water; surfactants, including anionic, cationic, nonionic, and zwitterionic surfactants; emulsifiers; emollients; humectants; conditioning agents for hair, skin, or nails; chelating agents; active agents; bleaching or whitening agents; pH adjusting agents; fragrances; colorants; exfoliating agents; antioxidants; botaniical ingredients, such as plant extracts; mica; smectite; thickening agents; rheology modifiers; oils; dyes; waxes; amino acids; nucleic acids; vitamins; hydrolyzed proteins and derivatives thereof; glycerol and derivatives thereof; enzymes; antiinflammatory and other medicinal agents; microbiocides; antifungals; antiseptics; antioxidants; UV absorbers; dyes and pigments; preservatives; sunscreen actives; antiperspirant actives; oxidizing agents; pH balancing agents; moisturizing agents; peptides and derivatives thereof; anti-aging actives; hair growth promoters; anti-cellulite actives; and other ingredients useful in human use formulations.

[0065] The formulations can include one or more bio-based C7 MGME compositions. In preferred embodiments, the type and amount of bio-based C7 MGME composition used in the embodiments of the formulations will provide an antimicrobial or microbiostatic effect in the formulation to protect the formulation from microbial contamination and / or improve antimicrobial efficacy on a surface (e.g., skin, hair, etc.). Accordingly, one embodiment includes a formulation containing at least one bio-based C7 MGME composition and at least one other ingredient. Another aspect of the present application includes a method of attenuating microbial contamination comprising blending an effective amount of at least one fully bio-based C7 MGME composition with at least one other ingredient to form a microbiostatic concentrate (MBC) that can be added to a formulation to protect the formulation from microbial contamination and / or improve antimicrobial efficacy on a surface. Embodiments of the formulation and / or MBC include a bio-based C7 MGME composition comprising a bio-based MGME of Formula (I):

[0066]

[0067] wherein R1, R2, and R3 are independently -H or -C(O)-C6 alkyl (e.g., n-heptanoyl).

[0068] The bio-based C7 MGME compositions of the present application can be present in the formulation at a concentration of about 0.05 wt% to about 10 wt% of the formulation. In the formulation, for example, in a formulation of a personal care product, the bio-based C7 MGME composition can be present, for example, in an amount of about 0.05 wt% to about 10 wt%, for example, 0.1 wt% to 5 wt%, 0.25 wt% to 4 wt%, or 0.25 wt% to 2.5 wt%. In terms of the upper limit, the amount of bio-based C7 MGME composition can be less than 10 wt%, for example, less than 5 wt%, less than 4 wt%, or less than 2.5 wt%. In terms of the lower limit, the amount of bio-based C7 MGME composition can be greater than 0.05 wt%, for example, greater than 0.1 wt%, greater than 0.2 wt%, or greater than 0.25 wt%. In certain embodiments, the compositions of the present application are present in the formulation at a concentration of about 0.25 wt% to about 2.5 wt% of the formulation.

[0069] Embodiments of the formulations can take the form of, for example, but not limited to, a solution; a conditioner for hair, nails, skin, or fabric; a shampoo; a hair gel; a mustache / beard oil or wax; a hair styling preparation; a permanent wave liquid; a hair colorant; a glaze; a skin lotion; a facial and body cleanser; a makeup remover; a cleansing lotion; an emollient lotion / cream; a soap bar; a shaving cream; a sunscreen; a sunburn treatment; a deodorant; a moisturizing gel; a shaving foam; a face powder; a foundation; a lipstick, a blush; an eyeliner; an anti- wrinkle anti-aging cream; an eye shadow; an eyebrow pencil; a mascara; a mouthwash; a toothpaste; an oral care composition; a skin cleansing composition; a fabric cleaning composition; a dish cleaning composition; a hair or fur cleaning composition; a deodorant or antiperspirant; a decorative cosmetic; or a hair styling composition. Certain embodiments can also include a micellar solution (which includes water and at least one surfactant), or an oil-in-water emulsion, and further include other forms that can be suitable for delivering a fully biobased C7 MGME composition for use, such as an aqueous solution or dispersion or a non-aqueous solution or a solid / semi-solid mixture.

[0070] The pH of the formulations and methods of preserving and mitigating microbial contamination as described herein can be, for example, from about 2 to about 10, such as from 3 to 9, or from 4 to 8. In terms of the upper limit, the pH can be less than 10, such as less than 9, less than 7, less than 6.5, less than 6, or less than 5.6. In terms of the lower limit, the pH can be greater than 2, such as greater than 3, greater than 4, or greater than 5. In certain embodiments, the pH is preferably less than about 6.5, more preferably less than about 6, and most preferably less than about 5.6.

[0071] Booster. In some embodiments, the formulations of the present application can include a booster, which is a compound that can be added to enhance the antimicrobial and / or preservative efficacy of the biobased C7 MGME composition, such as by enhancing the activity of the biobased C7 MGME in inhibiting bacteria and / or fungi. Suitable boosters for use in the compositions of the present application include, but are not limited to, polyols, glycerol ethers, chelating agents, and combinations thereof, all of which are preferably biobased.

[0072] Suitable polyols include, but are not limited to, C3 to C 10 Diols, which can include 1,2-alkanediols, 2,3-alkanediols, and mixtures thereof. In some embodiments, the one or more polyols include a vicinal C3 to C 10Diols, also known as mid-chain terminal diols. Non-limiting representative examples of polyols useful in the compositions of the present application include glycerin, propylene glycol, 1,2- propylene glycol, 1,2-butanediol, 1,3-butanediol, 1,4-butanediol, 2,3-butanediol, 1,2-hexanediol, 1,2-heptanediol, 2,3-octanediol, caprylyl glycol, decanediol, sorbitol, sorbitan, and the like, and mixtures thereof.

[0073] Suitable glyceryl ethers are typically monoethers of glycerol having one or more C6 to C 10 alkyl groups. Non-limiting representative examples of glyceryl ethers useful in the compositions of the present application include hexyl glyceryl, cyclohexyl glyceryl, heptyl glyceryl, octyl glyceryl ether, methyl heptyl glyceryl, ethyl hexyl glyceryl, and the like, and mixtures thereof.

[0074] Chelating agents include, but are not limited to, bio-based C6 to C 10 alkyl hydroxamic acids and their corresponding alkyl hydroxamate salts, such as heptanohydroxamic acid, caprylohydroxamic acid (caprylhydroxamic acid), pelargohydroxamic acid, caprohydroxamic acid, and mixtures thereof. Preferred is caprylohydroxamic acid (caprylhydroxamic acid) or its corresponding hydroxamate salt. Other non-limiting examples of chelating agents useful as enhancers include tetrasodium glutamate diacetate, citric acid / citrate, phytic acid / phytate, gluconic acid / gluconate, galacturonic acid / galacturonate, and galactaric acid / galactarate, and mixtures thereof.

[0075] Enhancers can also include organic acids such as benzoic acid, sorbic acid, p-anisic acid, levulinic acid, salicylic acid, citric acid, lactic acid, succinic acid, malonic acid, malic acid, fumaric acid, anisic acid, glycolic acid, their salts, and combinations thereof. Other enhancers include mid-chain (C6-C 10 ) fatty amides of the amino acid glycine, such as capryloyl glycine or its salts.

[0076] The enhancer can be present in an amount of from about 0.05 wt% to about 15 wt% (based on the total weight of the formulation), such as 0.075 wt% to 10 wt%, or 0.1 wt% to 5 wt%. In terms of upper limits, the amount of enhancer can be less than 15 wt%, such as less than 10 wt%, or less than 5 wt%. In terms of lower limits, the amount of enhancer can be greater than 0.05 wt%, such as greater than 0.75 wt%, or greater than 0.1 wt%.

[0077] Relevantly, the enhancer can be present in a formulation containing the microbial inhibiting concentrate of the present application.

[0078] Microbial Inhibiting Concentrate. The blend of C7 MGME comprising the enhancer can also be prepared into a microbial inhibiting concentrate (MBC) for addition to a composition to prevent microbial contamination and growth. The MBC includes at least the following ingredients: a bio-based C7 MGME composition as described above and at least one of glycerol and a C3-C4 diol. The C3-C4 diol can be selected from the group consisting of propylene glycol, 1,2-propanediol (propylene glycol), 1,3-propanediol, 1,2-butanediol, 1,3-butanediol, 2,3-butanediol, 1,4-butanediol, methylpropanediol, and combinations thereof.

[0079] The MBC can include from about 30 wt% to about 85 wt% of the bio-based C7 MGME composition of the present application and, for example, from about 5 wt% to about 50 wt% of at least one of glycerol or a C3-C4 diol. The MBC contains a bio-based C7 MGME composition including a compound of Formula (I) in a range of from about 30 wt% to about 85 wt%, for example, from 35 wt% to 80 wt%, from 40 wt% to 80 wt%, or from 45 wt% to 75 wt%. In terms of the upper limit, the amount of bio-based C7 MGME composition can be less than 85 wt%, for example, less than 80 wt%, or less than 75 wt%. In terms of the lower limit, the amount of bio-based C7 MGME composition can be greater than 30 wt%, for example, greater than 35 wt%, or greater than 40 wt%, or greater than 45 wt%.

[0080] The MBC contains glycerol, a C3-C4 diol, or a combination thereof in a range of from about 1 wt% to about 75 wt%, for example, from 1 wt% to 70 wt%, from 2.5 wt% to 50 wt%, from 5 wt% to 50 wt%, or from 5 wt% to 25 wt%. In terms of the upper limit, the amount of at least one of glycerol and a C3-C4 diol can be less than 75 wt%, for example, less than 70 wt%, less than 50 wt%, or less than 25 wt%. In terms of the lower limit, the amount of at least one of glycerol and a C3-C4 diol can be greater than 1.0 wt%, for example, greater than 2.5 wt%, or greater than 5 wt%.

[0081] In some embodiments, the MBC optionally comprises from about 0.1 wt% to about 20 wt% of a medium chain alkyl hydroxamic acid, a salt thereof, or a combination thereof. The MBC can comprise a medium chain alkyl hydroxamic acid, a salt thereof, or a combination thereof in a range of about 0.1 wt% to about 25 wt%, such as 1.0 wt% to 20 wt%, 2.5 wt% to 20 wt%, 5.0 wt% to 17.5 wt%, or 5.0 wt% to 15 wt%. In terms of the upper limit, the amount of the medium chain alkyl hydroxamic acid, a salt thereof, or a combination thereof can be less than 25 wt%, such as less than 20 wt%, less than 17.5 wt%, or less than 15 wt%. In terms of the lower limit, the amount of the medium chain alkyl hydroxamic acid, a salt thereof, or a combination thereof can be greater than 0.1 wt%, such as greater than 1.0 wt%, greater than 2.5 wt%, or greater than 5.0 wt%.

[0082] As described below, other optional ingredients can be included in the MBC. The MBC can optionally contain any of the other enhancer compounds described above, including but not limited to glycerol ethers, organic acids, chelating agents, and combinations thereof, all of which are preferably bio-based. In some embodiments, the MBC is substantially anhydrous, i.e., no water has been intentionally added to the MBC at the time of manufacture, and the MBC contains less than about 2 wt% water, such as adventitious moisture from processing or from atmospheric absorption.

[0083] The MBC can then be used in subsequent formulations, such as formulations for personal care products. The MBC can be present in the formulation, for example, in an amount of about 0.1 wt% to about 10 wt%, such as 0.25 wt% to 7.5 wt%, 0.5 wt% to 5 wt%, or 0.75 wt% to 2.5 wt%. In terms of the upper limit, the amount of the MBC can be less than 10 wt%, such as less than 7.5 wt%, less than 5 wt%, or less than 2.5 wt%. In terms of the lower limit, the amount of the MBC can be greater than 0.1 wt%, such as greater than 0.25 wt%, greater than 0.5 wt%, or greater than 0.75 wt%.

[0084] The pH of the formulation comprising the MBC as described herein can be, for example, about 2 to about 10, such as 3 to 9, 4 to 8, 5 to 8, 5.5 to 7.5, or 6 to 7. In terms of the upper limit, the pH can be less than 10, such as less than 9, less than 8, less than 7.5, or less than 7. In terms of the lower limit, the pH can be greater than 2, such as greater than 3, greater than 4, greater than 5, greater than 5.5, or greater than 6. In certain embodiments, the pH is about 5 to about 8, preferably about 5.5 to about 7.5, or more preferably about 6 to about 7.

[0085] Formulations containing the present biobased C7 MGME composition or the present MBC can have superior antimicrobial properties or preservation. In some embodiments, formulations containing the present composition remain substantially free of microbial contamination for a period of at least 12 months, at least 18 months, or at least 24 months. Embodiments of formulations and / or compositions, and methods of preserving and mitigating microbial contamination can further include a 90% reduction in microorganisms within one week to one month. In some embodiments, the present composition can be used to reduce microorganisms within a formulation by at least 90% within seven days. In some embodiments, the present invention includes methods of adding a composition to a formulation to reduce or eliminate 99% of bacteria within seven days, and / or to reduce or eliminate 90% of yeast and fungi in a formulation within seven days.

[0086] In some embodiments, the present composition exhibits substantially similar antimicrobial preservation properties as a formulation containing the same amount or concentration of C8 to C10 glycerides, such as glyceryl caprylate. 14 Formulations containing the present composition exhibit superior optical clarity as measured by nephelometric turbidimetry as compared to formulations of glycerides, such as glyceryl caprylate. In some embodiments, formulations containing the present composition have adjustable turbidity. Turbidity can be measured by methods known in the art, such as in ISO 7027 (International Organization for Standardization, Geneva, Switzerland, 1997), which is incorporated herein by reference in its entirety. 14 The present formulation has the same or superior antimicrobial preservation properties as compared to a reference formulation of the present C7 MGME composition.

[0087] In some embodiments, the present composition exhibits substantially similar antimicrobial preservation properties as a formulation containing the same amount or concentration of C8 to C10 glycerides, such as glyceryl caprylate. 14 Formulations containing the present composition exhibit superior optical clarity as measured by nephelometric turbidimetry as compared to formulations of glycerides, such as glyceryl caprylate. In some embodiments, formulations containing the present composition have adjustable turbidity. Turbidity can be measured by methods known in the art, such as in ISO 7027 (International Organization for Standardization, Geneva, Switzerland, 1997), which is incorporated herein by reference in its entirety. The methods described in ISO 2016 (International Organization for Standardization) and using instruments such as the HF Scientific Micro100 benchtop turbidimeter operating at room temperature (23°C ± 2°C). In some embodiments, the turbidity value of the formulation comprising the composition of the present invention is less than about 100 nepelometric turbidity units (NTU), less than about 75 NTU, less than about 50 NTU, less than about 25 NTU, or less than about 10 NTU, said turbidity value being measured by ISO 7027 or a similar method. In some embodiments, the turbidity of the formulation comprising C7 bio-based monoglycerides as described herein may be less than about 10 nepelometric units (NTU). Turbidity is important so that the formulation can be readily formulated into a clear or transparent end-use product. Therefore, for a given formulation, the turbidity of the formulation herein should be as low as possible.

[0088] Example

[0089] Example 1. Comparison of bio-heptanoic acid and petro-heptanoic acid

[0090] pass 14 C7 radiocarbon dating and chromatographic analysis to determine the content of branched impurities, which are found only in petroleum heptanoic acid (i.e., non-biological / non-renewable heptanoic acid), thus confirming the source of C7 heptanoic acid.

[0091] According to ASTM D6866 14 C1 radiocarbon dating indicates that it is derived from castor oil. Arkema (ortho-heptanoic acid) contains 100% bio-based carbon, while petroleum heptanoic acid, obtained by hydroformylation of 1-hexene followed by oxidation to C7 acid (ortho-heptanoic acid, Oxea), contains 0% bio-based carbon.

[0092] Samples of bioheptanoic acid and petroleum heptanoic acid were reacted with methanol in the presence of boron trifluoride (BF3) to obtain methyl ester derivatives of the alkanoic acids. The resulting methyl ester compositions were then extracted into heptane and analyzed by gas chromatography using the AOCS Official Method Ce 1h-05 based Total Fatty Acid Methyl Ester (FAME) method. A Thermo Electron 1310 gas chromatograph equipped with an FID detector and Chromeleon software (version 7.2.10) and a Restek MX-5 column (0.53 mm ID, 30 m, 0.5 pm film thickness) was used. The injector and detector temperatures were 300 °C, the initial temperature was 100 °C, the final temperature was 300 °C, and the heating rate was 8 °C / min. The injection volume was 1.0 pL, the He carrier gas flow was 5 mL / min, and the split injection flow was 10 mL / min.

[0093] The GC analysis showed that the bioheptanoic acid contained greater than 99% straight chain C7 fatty acids and contained only trace amounts (about 0.1%) of straight chain C6 fatty acids as impurities. In contrast, the petroleum heptanoic acid contained a significant level of branched C7 alkanoic acid impurity, 2-methylhexanoic acid, present at about 2.9%.

[0094] Table 1. Characterization of bioheptanoic acid and petroleum heptanoic acid (Example 1)

[0095]

[0096] Reported relative peak areas for GC analysis as methyl ester derivatives.

[0097] Measured according to ASTM D6866.

[0098] Example 2. Synthesis of C7 MGME composition GH70

[0099] Into a 22 L four-necked round bottom flask equipped with an overhead mechanical stirrer and temperature controller, glycerol (9669 g, 105.1 mol) and bioheptanoic acid (GH70, 10000 g, 105.1 mol) were added with nitrogen sparge. N-heptanoic acid, Arkema, 6831 g, 52.55 mol). The contents of the flask were heated to 200 °C while stirring at a moderate rate. After 2 hours at 200 °C, the system was vacuumed to remove the condensing water. The reaction was continued until the desired conversion was reached (as indicated by an acid value < 1.0 mg KOH / g), which took about 9 hours. The reactor was then cooled to 80 °C. At 80 °C and 5 mm Hg vacuum, steam was sparged into the reactor for 2 hours. After stripping, the reactor was cooled to 70 °C under 5 mm Hg vacuum. The reactor was then brought to atmospheric pressure and the contents were discharged into a holding vessel for further processing.

[0100] An equal amount of deionized water (DI) was added to the reaction contents, the mixture was heated to 85-90 °C, and mixed vigorously for 15 minutes. Mixing was stopped and the mixture was allowed to separate into two layers. The bottom aqueous layer, which contained free glycerol, was removed and saved for glycerol recovery. The wash procedure was repeated using the same amount of DI water as the first separation, with the addition of 0.5% potassium chloride. In this second separation, the bottom aqueous layer was discarded. The organic phase (top layer) was charged into a 4-necked round bottom flask, heated to 90 °C, and dried under 5 mm Hg vacuum while mixing at a low to moderate rate for 5 hours. The reactor product was then cooled to room temperature and discharged into an appropriate container for storage.

[0101] The resulting bio-based glycerol heptanoate MGME composition contained 70.4 wt% glyceryl monoheptanoate, 25.1 wt% glyceryl diheptanoate, 2.9 wt% glyceryl triheptanoate, and 1.2 wt% free glycerol. The product of Example 2 is referred to as GH70, nominally indicating a glycerol heptanoate MGME composition comprising about 70 wt% glyceryl monoheptanoate and having an average glyceryl esterification degree = 1.29.

[0102] Example 3. Preparation of C7 MGME composition GH90

[0103] The GH70 product of Example 2 was charged into a feed flask and fed into a wiped film evaporator operating at 140 °C and 1 mm Hg vacuum. The GH70 product was fractionated to produce a C7 MGME composition comprising 91.7 wt% glyceryl monoheptanoate, 6.2 wt% glyceryl diheptanoate, and 0 wt% glyceryl triheptanoate. Example 3 is referred to as GH90, nominally indicating a glycerol heptanoate MGME composition comprising about 90 wt% glyceryl monoheptanoate and having an average glyceryl esterification degree = 1.04.

[0104] Comparative Examples 2 and 3. Preparation of C8 MGME compositions GC70 and GC90

[0105] A C8 MGME composition was prepared using a method similar to that described in Examples 2 and 3; however, bio-based C8 caprylic acid was used in place of bio-heptanoic acid. The resulting comparison is, for example, as follows:

[0106] Comparative Example 2. GC70 (nominally referred to as about 70 wt% monoglyceride caprylate) is a C8 MGME composition comprising 72.0 wt% monoglyceride caprylate, 22.9 wt% diglyceride caprylate, 2.1 wt% triglyceride caprylate, and 1.3 wt% free glycerol and an average glyceryl esterification degree = 1.22.

[0107] Comparative Example 3. GC88 (nominally referred to as about 88 wt% monoglyceride caprylate) is a C8 MGME composition comprising 89.2 wt% monoglyceride caprylate, 7.7 wt% diglyceride caprylate, 0.1 wt% triglyceride caprylate, and 2.9 wt% free glycerol and an average glyceryl esterification degree = 1.05.

[0108] Example 4. Improved skin mildness of C7 MGME compositions

[0109] Using MatTek EpiDerm TMSkin irritation testing (OECD TG 439) evaluates the skin mildness of the MGME compositions using an MTT assay to measure cell viability of 3-D skin tissue equivalents exposed to aqueous solutions of the MGME compositions as a function of time. Additional experimental details of the assay are described in the publications of Faller et al. (Predictive ability of reconstructed human epidermis equivalents for the assessment of skin irritation of cosmetics, Tox. In Vitro, 2002, 16(5), 557-572) and Walters et al. (In Vitro Assessment of Skin Irritation Potential of Surfactant-based Formulations by Using a 3-D Skin Reconstructed Tissue Model and Cytokine Response, Altern. Lab Anim., 2016, 44(6), 523-532). Cell viability as a function of time is a measure of cytotoxicity and correlates with the irritancy of the chemical composition. The exposure time to 50% cell viability is referred to as the ET 50 value, and is a characteristic measure indicative of skin irritation. The higher the ET 50 value of a chemical composition, the less cytotoxic the composition; thus, a composition having a higher ET 50 value is considered less irritating than a composition having a lower ET 50 value.

[0110] Table 2. Cell Viability and ET 50 values as a function of exposure time for 1.0 wt% solutions of the MGME compositions of Examples 2 and 3 and Comparative Examples 2 and 3

[0111]

[0112]

[0113] Table 2 lists the cell viability values as a function of exposure time for 1.0 wt% solutions of the MGME compositions of Examples 2 and 3 and Comparative Examples 2 and 3; also listed are the ET 50Values. As used in Table 2, "S.D." refers to the relative standard deviation, which was calculated from the cell viability (%) values evaluated by performing two experiments on each tissue sample using each of the example compositions and comparative compositions of Examples 2-3 and Comparative Examples 2-3.

[0114] Figure 1 Values as a function of exposure time. It should be noted that because the cytotoxicity of Comparative Example 3 was significantly greater, the 16 hour exposure time was replaced with a 1 hour exposure time in order to obtain data more suitable for accurate calculation of ET 50 Values. As used in Table 2, "S.D." refers to the relative standard deviation, which was calculated from the cell viability (%) values evaluated by performing two experiments on each tissue sample using each of the example compositions and comparative compositions of Examples 2-3 and Comparative Examples 2-3.

[0115] When compared to the corresponding C8 MGME compositions (GC70 and GC88) of Comparative Examples 2 and 3, the C7 MGME compositions (GH70 and GH90) of Examples 2 and 3 exhibited significantly higher cell viability at all exposure times. This is quite surprising given that these compositions differ by only one methylene (-CH2-) unit in the fatty acyl chain. The ET 50 Values of Examples 2 and 3 were all greater than 24 hours, while Comparative Examples 2 and 3 exhibited ET 50 Values of 20.1 hours and <1 hour, respectively, indicating that the C8 MGME compositions of Comparative Examples 2 and 3 were significantly more irritating than the C7 MGME compositions.

Claims

1. A bio-based monoglyceride preservative composition comprising: one or more compounds of Formula (I): （I）， wherein R1, R2, and R3 are independently -H or -C(O)-C6 alkyl; wherein the one or more compounds of Formula (I) comprise: greater than 65 wt% and less than 75 wt% glyceryl monoheptanoate; 2 wt% to 35 wt% glyceryl diheptanoate, glyceryl triheptanoate, or a combination thereof; and less than 30 wt% glycerol; at least 98% of the -C(O)-C6 alkyl groups present in the one or more compounds of Formula (I) are n-heptanoyl groups; and wherein the carbon present in the one or more compounds of Formula (I) is bio-based.

2. The composition of claim 1, wherein the concentration of glyceryl diheptanoate, glyceryl triheptanoate, or a combination thereof is 2 wt% to 30 wt%.

3. The composition of any one of claims 1 to 2, wherein the composition comprises less than 20 wt% glycerol.

4. The composition of any one of claims 1 to 2, wherein the average degree of glyceryl esterification of the composition is 1.0 to 1.

4.

5. The composition of any one of claims 1 to 2, wherein at least 99 % of the -C(O)-C6 alkyl groups in the composition are n-heptanoyl groups.

6. The composition according to any one of claims 1 to 2, wherein the ET value of the composition is greater than 24 hours when tested as a 1% aqueous solution of the composition according to the in vitro skin irritation test OECD 439. 50 value is greater than 24 hours.

7. The composition of any one of claims 1 to 2, wherein the composition has an MTT cell viability value at 24 hours of greater than 50 % when tested as a 1 % aqueous solution of the composition according to the in vitro skin irritation test OECD 439.

8. The composition of any one of claims 1 to 2, further comprising an enhancer selected from the group consisting of: one or more polyols, one or more glycerol ethers, one or more chelating agents, and combinations thereof.

9. A formulation comprising the composition of any one of claims 1 to 8, wherein the formulation has a shelf life against microbial contamination of at least 12 months, or at least 18 months, or at least 24 months; or wherein the formulation has the same or superior preservation against microbial contamination as compared to a reference formulation of a monoglyceride composition, due to the presence in the formulation of the composition of claim 1, and wherein the composition of claim 1 is present in the formulation in an amount of from 0.1 to 10% by weight of the formulation. 14 wherein the formulation has the same or superior preservation against microbial contamination as compared to a reference formulation of a monoglyceride composition, due to the presence in the formulation of the composition of claim 1, and wherein the composition of claim 1 is present in the formulation in an amount of from 0.1 to 10% by weight of the formulation. where wherein the formulation has a turbidity value of less than 100 NTU.

10. The formulation of claim 9, further comprising at least one ingredient selected from the group consisting of: water; surfactants, including anionic, cationic, nonionic, and zwitterionic surfactants; emollients; conditioning agents for hair, skin, or nails; chelating agents; active agents; bleaching or whitening agents; fragrances; exfoliating agents; botanical ingredients; mica; montmorillonite; thickening agents; rheology modifiers; oils; waxes; amino acids; nucleic acids; vitamins; hydrolyzed proteins and derivatives thereof; enzymes; anti-inflammatory and other pharmaceutical agents; disinfectants; UV absorbers; dyes and pigments; preservatives; oxidizing agents; pH balancing agents; humectants, and combinations thereof.

11. The formulation of claim 9, further comprising at least one ingredient selected from the group consisting of: humectants; additional pH adjusting agents; colorants; microbiocidal agents; sunscreen active agents; antiperspirant active agents; anti-aging actives; hair growth promoters; emulsifiers; anti-cellulite active agents, and combinations thereof.

12. The formulation of claim 9, further comprising at least one ingredient selected from the group consisting of: antifungal agents; peptides and derivatives thereof; and combinations thereof.

13. A method of preserving a formulation against microbial contamination, comprising adding to the formulation a sufficient amount of the composition of any one of claims 1 to 8.

14. A microbial inhibiting concentrate comprising: the bio-based monoglyceride preservative composition of claim 1 in an amount of 30 wt% to 85 wt%, and at least one of glycerol and a C3-C4 diol in an amount of 1 wt% to 70 wt%.

15. The composition of claim 8 or the formulation of claim 9 or the microbial inhibiting concentrate of claim 14, further comprising one or more polyols selected from the group consisting of: glycerol, propylene glycol, 1,2-propanediol, 1,2-butanediol, 1,3-butanediol, 1,4-butanediol, 2,3-butanediol, 1,2-hexanediol, 1,2-heptanediol, 2,3-octanediol, 1,2-octanediol, decanediol, sorbitol, sorbitan, and combinations thereof.

16. The composition of claim 8 or the formulation of claim 9 or the microbial inhibiting concentrate of claim 14, further comprising one or more glyceryl ethers selected from the group consisting of: hexyl glyceryl, cyclohexyl glyceryl, heptyl glyceryl, octyl glyceryl ether, methyl heptyl glyceryl, ethyl hexyl glyceryl, and combinations thereof.

17. The composition of claim 8 or the formulation of claim 9 or the microbial inhibiting concentrate of claim 14, further comprising one or more chelating agents selected from the group consisting of: heptyl hydroxamic acid and salts thereof, octyl hydroxamic acid (caprylyl hydroxamic acid) and salts thereof, pelargonyl hydroxamic acid and salts thereof, citric acid and salts thereof, hexacarbonyl hydroxamic acid and salts thereof, glutamic acid diacetic acid tetrasodium, phytic acid and salts thereof, gluconic acid and salts thereof, galacturonic acid and salts thereof, and galactaric acid and salts thereof, and combinations thereof.

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