CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Patent Application Serial No. 63/331 ,528, filed April 15, 2022; the entire contents of which are herein incorporated by reference.

TECHNICAL FIELD

This disclosure relates to personal care products and methods of production thereof.

BACKGROUND

Natural emulsifiers have recently become of interest to both the food and personal care industries due to consumers’ preference for more natural products. Generally speaking, a personal care product, such as a cosmetic, or a food product can be considered as natural if it is composed of only natural raw materials. Most emulsifiers, however, are obtained from non-sustainable sources. Moreover, polymeric materials represent a major class of ingredients in cosmetic products, acting as thickeners, emulsifiers, film formers, conditioners, moisturizers, and emollients, and the like. A large number of thickeners are polymers which are able to modify the rheological profile of a formulation, capture water, and deliver active compounds.

Emulsions are commonly used in product development in several industries, particularly in the cosmetics and food industries. Several factors affect emulsion stability and properties. Hydrophilic polymers are widely used to produce emulsions as thickeners, stabilizers, emulsifiers, and moisturizers. Conventionally, carboxymethylcellulose is used in the cosmetic industry as a thickener and rheology modifier. However, carboxymethylcellulose is an anionic polymer derived by the carboxymethylation of cellulose and ill-suited as an emulsifier due to its inability to reliably obtain a stable emulsion. Carboxymethylation is a reaction by which carboxylic acid groups replace at least some of the hydroxyl groups of the polysaccharide cellulose molecule. Holocellulose, on the other hand, is found in many biological materials and is composed of cellulose and hemicellulose. Conventionally, holocellulose is typically carboxym ethylated to enhance its water solubility and not to develop an emulsifier suitable for the cosmetic or food industry. Moreover, most lignocellulosic-derived ingredients cannot be used in cosmetics using conventional processes because of color issues.

It is therefore desirable to have an improved new emulsifier based on the holocellulose molecule that is natural, sustainable and addresses the various unmet needs described above and other shortcomings of conventional products and processes.

SUMMARY

The present disclosure relates to carboxym ethylated holocellulose [CMH], wherein the holocellulose can be obtained from sugarcane bagasse. CMH is a hydrophilic polymer with thickening, stabilizing, and emulsification properties, which can be particularly useful in the cosmetic and food industries. Additional embodiments relate to compositions of matter comprising a personal care product, such as a cosmetic, food, and animal feed products comprising amounts of the above described CMH, methods of improving personal care products, and articles of manufacture. Optionally, each can comprise packaging material containing any of the abovedescribed products or compositions, wherein each packaging material contains instructions for the use thereof.

Provided herein are carboxym ethylated holocelluloses or salts thereof, wherein the holocellulose is derived from sugarcane bagasse.

Also provided herein are methods of producing a carboxym ethylated holocellulose that include: delignifying sugarcane bagasse with a first alkaline hydrogen peroxide, separating the delignified holocellulose, and delignifying the separated sugarcane bagasse with a second alkaline hydrogen peroxide.

Also provided herein are compositions adapted for admixture with a personal care product, wherein the composition comprises the carboxymethylated holocellulose and a compatible carrier. In some embodiments, said personal care product is a cosmetic.

Also provided herein are compositions including the carboxym ethylated holocellulose. In some embodiments, the composition includes a personal care product, and optionally wherein said personal care product is a cosmetic.

Also provided herein are compositions including a personal care product and any of the compositions adapted for admixture with a personal care product. In some embodiments, said personal care product is a cosmetic.

Also provided herein are methods of enhancing the properties of a personal care product that include admixing therewith any of the carboxymethylated holocelluloses described herein and any of the compositions adapted for admixture with a personal care product. In some embodiments, said personal care product is a cosmetic.

Also provided herein are articles of manufacture including packaging material including any of the carboxymethylated holocelluloses described herein, said packaging material containing instructions for the use thereof.

Also provided herein are articles of manufacture including packaging material containing any of the compositions adapted for admixture with a personal care product described herein, said packaging material containing instructions for the use thereof.

Also provided herein are food additive compositions including any of the carboxym ethylated holocelluloses described herein. In some embodiments, said holocellulose is produced according to any of the methods described herein.

Also provided herein are methods of enhancing the properties of a food product including admixing therewith any of the carboxymethylated holocelluloses described herein.

Also provided herein are methods of enhancing the properties of a food product including admixing therewith any of the compositions adapted for admixture with a personal care product described herein.

Also provided herein are emulsifiers including any of the carboxymethylated holocelluloses described herein. In some embodiments, said holocellulose is produced by first delignifying sugarcane bagasse with a first alkaline hydrogen peroxide, separating the delignified holocellulose, and again delignifying the separated sugarcane bagasse with a second alkaline hydrogen peroxide.

Also provided herein are compositions including an emulsifier and a carrier, wherein the emulsifier includes any of the carboxym ethylated holocelluloses described herein. In some embodiments, the emulsifier is present at a concentration from about 0.1% to 10%. In some embodiments, the carrier is selected from the group consisting of squalane, hemisqualane, or a combination thereof. In some embodiments of any of the compositions described herein, the composition further includes an emollient, an active compound, or a combination thereof. In some embodiments of any of the compositions described herein, the composition is an emulsion.

BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 is a block diagram of one non-limiting method of preparing a carboxym ethylated holocellulose.

Fig. 2 is a bar graph showing IL6 expression in immortalized human keratinocyte HaCaT cells after incubation with SRM pollution particles and showing the CMH antipollution effect. Control corresponds to cells exposed to pollution particles. Significance of the results is indicated according to P values with one, two, three, or four of the symbols (*) corresponding to 0.01<P<0.05; 0.001 <P< 0.01 ; 0.0001 <P<0.001 ; and P<0.0001 , respectively.

Fig. 3 is a bar graph showing IL1 a expression in HaCaT cells after incubation with SRM pollution particles and showing the CMH antipollution effect. Control corresponds to cells exposed to pollution particles. Statistical analysis results are presented as *, corresponding to 0.01<P<0.05, as compared to control.

Fig. 4A is a bar graph showing pH fold change (%) of skin parameters for 1 .5% CMH, 2% CMH, and a benchmark emulsifier at 3%.

Fig. 4B is a bar graph showing transepidermal water loss (TEWL) fold change (%) of skin parameters for 1 .5% CMH, 2% CMH, and a benchmark emulsifier at 3%.

Fig. 4C is a bar graph showing hydration fold change (%) of skin parameters for 1 .5% CMH, 2% CMH, and a benchmark emulsifier at 3%. Fig. 4D is a bar graph showing erythema fold change (%) of skin parameters for 1 .5% CMH, 2% CMH, and a benchmark emulsifier at 3%.

DETAILED DESCRIPTION

Sugarcane bagasse is the lignocellulose biomass remaining after sugarcane juice extraction and is usually burned to generate steam and electric energy. However, the bagasse is also exploited for the production of cellulose, ethanol, pulp and paper, boards, animal feed, and furfural and its derivatives. Sugarcane bagasse is mainly composed of cellulose (~45-50%), hemicellulose (~25-30%), lignin (~25%) distributed in a lamellar structure, and a small amount of extractives and ashes (~2.4-9%). Holocellulose is the delignified mixture of cellulose and hemicellulose. In order to produce holocellulose from sugarcane bagasse, it can be treated to disrupt the cellulose-hemicellulose-lignin matrix and disrupt lignin recalcitrance, thereby rendering the holocellulose more accessible. In some embodiments, the holocellulose derived from sugarcane bagasse has a relative composition or relative ratio of cellulose and hemicellulose as found in sugarcane bagasse.

Delignification of bagasse can be accomplished by any one or combination of different physical, chemical, or biological processes. The present disclosure considers several protocols for alkaline hydrogen peroxide (AHP) delignification at different temperatures (e.g., about 25°C, 70°C, 80°C, and 210°C) and different peroxide concentrations (e.g., about 7.35%, 1%, 2%, and 0.6:1 (w/w)). Furthermore, the present disclosure is based, in part, on the surprising discovery that a carboxymethylated holocellulose superior to those produced heretofore as emulsifying agents can be synthesized by employing as a starting material holocellulose derived by delignifying sugarcane bagasse.

Briefly, according to one non-limiting embodiment, the bagasse is first delignified and bleached with a solution having mild alkaline (e.g., about 1 % (w/w) to 5% (w/w)) and peroxide concentrations (e.g., about 1 % (v/v) to 10% (v/v)), washed (e.g., with an aqueous solvent, such as water), and again subjected to the same mild alkaline/peroxide treatment. The thus produced delignified holocellulose is then activated by treatment with an alkali (e.g., such as NaOH) and 2-propanolol that promotes polymer swelling and decreases its crystallinity therefore making hydroxyl groups more available, followed by carboxymethylation with mono-chloroacetic acid or a salt thereof (e.g., a sodium salt) in a solvent (e.g., a polar solvent, such as isopropyl alcohol (IPA) or ethanol).

More particularly, while other embodiments are described in the following examples, it being understood by those skilled in the art that neither the foregoing brief description nor the following examples are to be taken in a limiting sense, but are made merely for the purpose of illustrating the general principles of the present disclosure. In the examples set forth below, the starting bagasse materials are set forth in batches and described below in Table 1 .

Table 1: Chemical characterization of sugarcane bagasse batches.

* Sugarcane bagasse is often shipped with 36-40% of moisture content and should be oven dried overnight at 40°C to reduce the water content to 5-10%.

Each of the bagasse batches listed in Table 1 were employed as starting materials in the following process, the steps of which are depicted in Fig. 1. Step 1 of the process (not shown in Fig. 1 ) comprises reducing the particle size of the bagasse by milling. Other processes can be employed, such as grinding, comminuting, pulverizing, or otherwise reducing the particle or fiber size of the bagasse.

As shown in Fig. 1 , in Step 2, the bagasse batch was dispersed in an agitation tank in 2% (w/w) sodium hydroxide at 85°C with agitation, followed by the slow addition of hydrogen peroxide (final concentration of 5.5% (v/v)), and allowed to react for 30 minutes to produce a partially delignified holocellulose. The ratio of bagasse to NaOH/H ₂ O ₂ was 1 :14.

In Step 3, the reaction product is conveyed to the filtration system, where the solid holocellulose was separated from the liquid waste stream and washed with distilled water for 1 hour.

In Step 4, the separated holocellulose was then conveyed to an agitation tank similar to that employed in Step 2, and the process of step 2 was repeated.

In Step 5, the filtration and washing of the product of Step 4, e.g., as depicted in Step 3, was repeated.

In Step 6, the bleached holocellulose is optionally dried, via air drying or other applicable methods, and minced. Moreover, according to one embodiment described herein, the process according to Fig. 1 is continuous from wet holocellulose, and the process disclosed proceeds directly from Step 5 to Step 7.

According to the embodiment in Step 7, the washed holocellulose of Step 5 (or minced holocellulose of Step 6) is conveyed to a heating tank and activated with 2- propanolol (1 :6 (w:v)) and sodium hydroxide 30% (1 :6 (w:v)) at 60°C for 5 hours with very slow agitation, followed by derivatization with chloroacetic acid (1 :2.2 (w:w)) at 60°C for 4 hours with mild agitation. The amount of 2-propanolol and sodium hydroxide can be provided in any amount, such as from about 1 :2, 1 :3, 1 :4, 1 :5, 1 :6, 1 :7, 1 :8, 1 :9, 1 :10 (w:v), as well as ranges there between (e.g., from about 1 :2 (w:v) to 1 : 10 (w:v)). The chloroacetic acid may be present as a salt (e.g., a sodium or potassium salt); and this agent may be substituted with another carboxymethylation reagent (e.g., a haloacetic acid, such as iodoacetic acid), which can optionally be present in an aqueous solution (e.g., an aqueous NaOH) or a polar solvent (e.g., water, alcohol, or a combination thereof). In Step 8, the reaction mixture of Step 7 is removed from heat and neutralized with acetic acid (e.g., pH 5.5 to pH 7.4) with agitation. The mixture is precipitated by the addition of ethanol (e.g., EtOH 96% or 99.8%) to obtain a final concentration of 60%.

In Step 9, the precipitated CMH is filtered and washed with hot 70% ethanol to yield the final product. In Step 10, the washed CMH is optionally dried to remove any remaining traces of water and ethanol, by any suitable method, with air drying being one example of a drying method.

CMH ingredient characterization

The product produced according to one embodiment disclosed herein is characterized below in Table 2. As disclosed, CMH ingredient characterization of that product was carried out as follows:

Purity: The purity of CMH samples was evaluated according to the standard method D1439-15 (ASTM, 2015) for “standard test methods for sodium carboxymethylcellulose”. According to one embodiment disclosed herein, 3 ± 0.1 g of each sample “as-received” to the nearest 0.001 g was placed in a beaker and stirred with two portions of 150 mL of ethanol at 60°C (80% (v/v)) for 15 minutes. The supernatant was properly decanted at the end of each step. The undissolved matter was then dried and weighed to calculate the percentage of CMH on a dry weight basis.

Substitution degree: The evaluation of the substitution degree of CMH was made according to the standard method D1439-15 (ASTM, 2015) for “standard test methods for sodium carboxymethylcellulose”.

Molecular weight: Molecular weight of CMH was determined by Size Exclusion Chromatography, using an Agilent 1260 Infinity II LC System coupled to a Refractive Index Detector. A PL aquagel-OH Mixed-M, 4.6 x 250 mm, 8pm and a PL aquagel-OH, 7.5 x 300 mm, 5 pm columns, at 30°C, coupled to a pre-column, were run at a flow of 0.5 mL/ min with ultrapure water as eluent. Pullulan P-82 standards Shodex (Showa Denko K. K., Tokyo, Japan), ranging from P-5 (5.9 kDa) to P-800 (708 kDa), were used to calibrate the method.

Appearance and colour: CMH appearance was evaluated by visual analysis. Solubility in water: The solubility of CMH was determined following the OECD Guidelines for the Testing of Chemicals, Section 1 - Test 105 - Water solubility, by flask method. In brief, 1.5 g of CMH was dissolved in 10 mL of water and incubated at 30°C with agitation for 24 hours. Then, undissolved particles were pelleted by centrifugation, and the supernatant was removed. The pellet was dried in the oven at 105°C for 24h and weighed. The solubility was calculated following the formula: (w ₁ — w ₇ ) Solubility (%) = - x 100 w _± where:

Wi is the initial mass of CMH and W2 is the weight of undissolved CMH pellet.

Powder X-Ray Diffraction Analysis (PXRD): Powder X-Ray Diffraction Analysis (PXRD) was performed on a Rigaku MiniFlex 600 diffractometer with Cu ka radiation, with a voltage of 40 kV and a current of 15 mA (3° < 29 > 60°; step of 0.01 and speed rate of 3.07min). The evaluation of the crystallinity index (%CI) was performed based on the profile and the baseline adjustment of the diffractogram based on reflection areas by amorphous subtraction using the program SmartLab Studioll from Rigaku® (version 4.3.287.0). All measurements were done in triplicate.

Moisture: Moisture content was determined by gravimetry according to standard methods (Methods 2540; APHA, 1998).

Table 2: Results of physicochemical characterization of the CMH ingredient.

CMH performance characterization

According to one embodiment disclosed herein, an oil and water (O/W) emulsion was prepared using CMH as an emulsifier according to the following formulation with reference to Table 3:

Emulsion formulation:

1. Heat Phase A and Phase C at 60°C.

2. Mix phase B.

3. Add Phase B into Phase A, with mixing. 4. Add Phase C into Phase A+B with high speed mixing. Mix for 5-7 minutes.

5. Cool batch with slow mixing until 35°C or below.

6. Adjust pH if necessary.

7. Add Phase D.

Table 3: O/W emulsion formulation using CMH as emulsifier.

Based on the formulation described above and shown in Table 3, the immediate stability was assessed visually by the appearance of phase separation and/or coalescence of the emulsion and prolonged stability according to ISO/TR 18811 .

Performance of the CMH produced according to the present disclosure is described below in Table 5. The produced CMH performance as an emulsifier was evaluated empirically to characterize its ability to form a stable emulsion. As disclosed, CMH performance characterization as emulsifier was carried out as follows:

Recommended use level: The CMH performance at different concentrations were tested following the O/W emulsion formulation disclosed above and using different CMH concentrations. The stability of the resulting emulsion was evaluated as described above.

Recommended temperature: The CMH performance at different temperatures were tested following the O/W emulsion formulation disclosed above and adjusting the temperature of the protocol from 50°C to 75°C. The stability of the resulting emulsion was evaluated as described in Table 5.

Electrolyte tolerance: The electrolyte tolerance of CMH based emulsions was assessed following the O/W emulsion formulation disclosed above with the incorporation of sodium chloride at 0.1 %, 0.5%, and 1 % (final concentration) in the water phase (Phase A, Table 3). The stability of the resulting emulsion was evaluated as described in Table 5. pH tolerance: The electrolyte tolerance of CMH based emulsions was assessed following the O/W emulsion formulation disclosed above at pH ranging from 2 to 10. The pH value of the water phase (Phase A, Table 3) of the formulation disclosed above was adjusted to the desired pH value by the addition of HCI 0.1 M and NaOH 0.1 M solutions. After, that, the formulation disclosed above was performed as described above (see CMH performance characterization section disclosed herein). The stability of the resulting emulsion was evaluated as described in Table 5. Direct Peptide Reactivity Assay (DPRA): The DPRA is an in chemico method, which quantifies the depletion of lysine and cysteine after 24 hours incubation with a test chemical at 25°C ± 2.5°C. Quantification of cysteine and lysine concentration is measured by high-performance liquid chromatography (HPLC) with gradient elution and UV detection at 220 nm. The protocol is based in OECD Guidelines for the testing of chemicals, section 4, Test 442C.

Emulsion Viscosity: The emulsion dynamic viscosity was evaluated in an AND SV-10 vibro viscometer.

Oil load capability: To evaluate the amount of oil phase that CMH is able to emulsify, different oil and water (O/W) emulsions were prepared using CMH as emulsifier at different concentrations, according to the following formulation with reference to Table 4:

Emulsion formulation:

1 . Mix emulsifier in water phase.

2. Heat water phase and oil phase at 60°C - 65°C.

3. Mix water phase.

4. Add oil phase to water phase with high speed and mix.

5. Cool batch with slow mixing until 35°C or below.

6. Adjust pH if necessary.

7. Add preservative.

Table 4: O/W emulsion formulations with increasing oil phase, using CMH as emulsifier at different concentrations.

Based on the formulation described above and shown in Table 4, CMH is able to emulsify up to 30% oil phase at 3, 4, or 5%.

Table 5 provides a summary showing CMH performance as an emulsifier.

Table 5: Characterization of CMH performance as emulsifier.

Antipollution effect

HaCaT cells (CLS Cell Lines Service GmbH, Eppelheim, Germany, Lot no. 300493-4619) were cultured in Gibco Dulbecco's Modified Eagle Medium (DMEM) supplemented with FBS (Cat. no. 10082-147, Gibco™, Thermo Fisher Scientific Inc., Waltham, MA, USA), penicillin (100 U/mL)-streptomycin (100 pg/mL) (Cat. no. 15240- 062, Gibco™). Cells were maintained at 37°C in a 5% CO2 humidified atmosphere. Detachment of confluent cells was achieved by a 5 minutes incubation in TrypLE™ Express Enzyme (1X), phenol red (Cat. no. 12605036, Gibco™). Cells were resuspended and counted using 0.4% Trypan Blue (Product no. T8154-20ML, Sigma- Aldrich, St. Louis, MO, USA) and the Countess II FL Automated Cell Counter (Invitrogen™, Thermo Fisher Scientific Inc.). HaCaT cells were seeded at 1 x 10 ⁵ cells/well in a 24 well plate. Cells were allowed to expand for 24 hours. Then, cells were incubated with pollution particles (SRM; Urban particulate matter NIST® SRM® 1648a) at 500 pg/ml concentration with CMH.

Medium supernatants were collected and used to evaluate the levels of proinflam matory cytokines IL-6 and 111 a by ELISA (BioLegend, Inc., San Diego, CA, USA). Cells were lysed with water and used for protein quantification via BCA method (Thermo Fisher Scientific Inc.). The results were expressed in pg of cytokine/mg of total protein. At least two independent experiments were performed.

Data were plotted and treated using GraphPad Prism version 6.00 (GraphPad Software, La Jolla, CA, USA). Data were further analyzed for significant differences. Multiple comparison tests were performed by one-way ANOVA supplemented with Tukey’s HSD post-hoc test. Differences were considered statistically significant at P < 0.05. Significance of the results is indicated according to P values with one, two, three, or four of the symbols (*) corresponding to 0.01 <P<0.05; 0.001 <P< 0.01 ;

0.0001 <P<0.001 ; and P<0.0001 , respectively.

HaCaT cells were exposed to pollution particles that induce an inflammatory effect. When incubated with pollution particles, the production of inflammatory cytokines is significantly higher (Fig. 2 and Fig. 3). However, when cells were incubated with the same stimulus in the presence of CMH, the production of inflammatory cytokines is significantly reduced (Fig. 2 and Fig. 3). Therefore, CMH inhibited the production of inflammatory cytokines - e.g., IL6 and IL1 a - in HaCaT cells, demonstrating a non-limiting anti-pollution effect. In vivo efficacy

The study, which was performed in the laboratory of the Escola Superior de Biotecnologia of Universidade Catolica Portuguese, involved 25 female subjects between the ages of 26 and 55 years old. Skin physiological parameters of moisture, transepidermal water loss (TEWL), pH, and erythema were measured to assess the effect of the emulsifier on skin barrier function. Two different formulations with 1 .5% (w/w) and 2% (w/w) of CMH were compared to a benchmark emulsifier at 3%.

Table 6: Composition of formulations used for in vivo efficacy.

Formulations were applied once in standardized delimited areas of the inner forearm. Measurements were taken under standardized room conditions (20°C and 50% relative humidity), after an acclimatization period of 30 minutes.

The Corneometer® CM 825 (Courage & Khazaka, Cologne, Germany) is a reliable method for determining the moisture level of the skin surface. It was possible to measure the skin surface pH value with a Skin-pH-Meter® PH 905 (Courage & Khazaka). TEWL was assessed by evaporimetry (Tewameter® TM 300; Courage & Khazaka). Erythema was evaluated by a Mexameter® M X16 probe (Courage & Khazaka).

The data in Figs. 4A-4D show that CMH formulations promoted an increase in stratum corneum moisture - similar to the benchmark formulation without significant statistical differences. Formulations containing 1.5% CMH promoted a decrease in TEWL, which was statistically significant as compared to the benchmark (Fig. 4B). TEWL is considered to be one useful measure of epidermal barrier function. A decrease in TEWL is an indicator of the promotion of integrity of the barrier. Therefore, CMH formulations had a positive impact on restoring the integrity of the skin barrier.

Regarding pH, CMH formulations did not impact the pH values of the skin in a statistically significant manner, as compared to benchmark (Fig. 4A). Regarding hydration fold changes, CMH formulations did not promote statistically significant changes, as compared to the benchmark (Fig. 4D). CMH formulations promoted a decrease in skin erythema that was concentration dependent, although not statistically significant as compared to the benchmark (Fig. 4D). Compositions

The present disclosure encompasses a composition having a carboxym ethylated holocellulose (CMH) (e.g., any described herein) or a salt thereof. Non-limiting salts include a sodium salt, a potassium salt, a calcium salt, and the like.

Any useful amount of CMH can be present within a composition. Non-limiting amounts include concentrations of up to about 5% (w/v) or from about 0.1 % to 5% (w/v), 0.5% to 5% (w/v), 1 % to 5% (w/v), 2% to 5% (w/v), 3% to 5% (w/v), 4% to 5% (w/v), 0.1 % to 4% (w/v), 0.5% to 4% (w/v), 1 % to 4% (w/v), 2% to 4% (w/v), 3% to 4% (w/v), 0.1 % to 3.9% (w/v), 0.5% to 3.9% (w/v), 1 % to 3.9%(w/v), 2% to 3.9% (w/v), 0.1 % to 3.5% (w/v), 0.5% to 3.5% (w/v), 1 % to 3.5%(w/v), 2% to 3.5% (w/v), 0.1 % to 3% (w/v), 0.5% to 3% (w/v), 1 % to 3%(w/v), 2% to 3% (w/v), 0.1 % to 2% (w/v), or 0.5% to 2% (w/v). In some embodiments, the CMH can be present in an amount from about 0.01 % to 50% (v/v) (e.g., from about 0.01 % to 0.1 % (v/v), 0.01 % to 1 % (v/v), 0.01 % to 5% (v/v), 0.01 % to 10% (v/v), 0.01 % to 20% (v/v), 0.01 % to 30% (v/v), 0.01 % to 40% (v/v), 0.1 % to 1 % (v/v), 0.1 % to 5% (v/v), 0.1 % to 10% (v/v), 0.1 % to 20% (v/v), 0.1 % to 30% (v/v), 0.1 % to 40% (v/v), 0.1 % to 50% (v/v), 1 % to 10% (v/v), 1 % to 15% (v/v), 1 % to 20% (v/v), 1 % to 30% (v/v), 1 % to 40% (v/v), 1 % to 50% (v/v), 5% to 10% (v/v), 5% to 15% (v/v), 5% to 20% (v/v), 5% to 30% (v/v), 5% to 40% (v/v), 5% to 50% (v/v), 10% to 15% (v/v), 10% to 20% (v/v), 10% to 30% (v/v), 10% to 40% (v/v), 10% to 50% (v/v), 15% to 20% (v/v), 15% to 30% (v/v), 15% to 40% (v/v), 15% to 50% (v/v), 20% to 25% (v/v), 20% to 30% (v/v), 20% to 40% (v/v), (v/v), 20% to 50% (v/v), 25% to 30% (v/v), 25% to 40% (v/v), 25% to 50% (v/v), 30% to 35% (v/v), 30% to 40% (v/v), 30% to 50% (v/v), 35% to 40% (v/v), 35% to 45% (v/v), or 35% to 50% (v/v)). In some embodiments, the amount can be determined based on the weight or volume of CMH and the weight or volume of a carrier or other material.

In some embodiments, the CMH aids the dispersal of oil (in the case of oil-in- water emulsions) and water (in the case of water-in-oil emulsions), respectively, into droplets of a small size and helps to maintain the particles in a dispersed state. In particular embodiments, the amount of CMH in the composition is provided in an effective amount to provide such dispersal. The composition can have any useful form, such as a water-in-oil emulsion, cream, liquid, gel, oil, paste, ointment, suspension, foam, lotion, oil-in-water emulsion, water-in-oil-in-water emulsion, water-in-silicone emulsion, powders, feeds, granules, and the like. In some embodiments, the composition can include one or more carriers, active compounds, and/or other components, as described herein.

Carriers and other components

The carriers herein can include any compatible substance for use with CMH. In some non-limiting embodiments, a carrier refers to a compound or a combination of compounds that facilitates the delivery of CMH to the skin of a subject.

Non-limiting examples of carriers include water, saline, buffers, alcohols (e.g., ethanol, propylene glycol, glycol, and the like), polyols (e.g., glycerol, propylene glycol, liquid polyethylene glycol, and the like), sugars (that can optional be in a sugar solution, e.g., aqueous dextrose), fatty acids (e.g., oleic acid, lauric acid, palmitic acid, stearic acid, linoleic acid, arachidic acid, and the like), oils (e.g., petroleum, animal, vegetable, or synthetic oil, including peanut oil, soybean oil, and mineral oil), and the like.

Other examples of carriers include squalane and mixtures of squalane and hemisqualane. Other carriers include derivatives of squalane including squalene, neosqualane, and isosqualene. As used herein, “squalane” refers to a compound having the following formula:

As used herein “hemisqualane” or “farnesane” refers to a compound having the following structure: or a stereoisomer thereof.

As used herein, “iso-squalane” or “isosqualane” refers to a compound having the following formula: As used herein, “neosqualane” refers to a compound having the following formula:

As used herein, “squalene” refers to a compound having the following formula:

As used herein, “iso-squalene” or “isosqualene” refers to a compound having any one of the following structures:

Compositions disclosed herein may comprise various amounts per weight of a carrier comprising squalane. Examples include 10% (w/w), 15% (w/w), 20% (w/w), 25% (w/w), 30% (w/w), 35% (w/w), 40% (w/w), 45% (w/w), 50% (w/w), 55% (w/w), 60%

(w/w), 65% (w/w), 70% (w/w), 75% (w/w), 80% (w/w), 85% (w/w), 86% (w/w), 87%

(w/w), 88% (w/w), 89% (w/w), 90% (w/w), 91 % (w/w), 92% (w/w), 93% (w/w), 94%

(w/w), 95% (w/w), 96% (w/w), 97% (w/w), 98% (w/w), 99% (w/w), 99.1 % (w/w), 99.2% (w/w), 99.3% (w/w), 99.4% (w/w), 99.5% (w/w), 99.6% (w/w), 99.7% (w/w), 99.8% (w/w), and 99.9% (w/w) carrier comprising squalane. In some embodiments, the composition can include at least 90% (w/w) of carrier comprising squalane.

Yet other examples of carriers include cosmetic bases, such as an oleaginous base, an emulsifiable base, an emulsion base (e.g., a water-in-oil base or an oil-in-water base), or a water-soluble base. See, e.g., Remington: The Science and Practice of Pharmacy, 19th Ed. (Easton, Pa.: Mack Publishing Co., pp. 1301-1306 (1985). Oleaginous bases include, for example, vegetable oils, synthetic oleaginous esters of carboxylic acids and alcohols, fats obtained from animals, semisolid hydrocarbons obtained from petroleum, and the like.

Examples of oleaginous cosmetic bases include white ointment, yellow ointment, cetyl esters wax, paraffins, petrolatum, white petrolatum, white wax, yellow wax, beeswax, and the like, as well as mixtures thereof. Emulsifiable cosmetic bases, also known as absorbent ointment bases or anhydrous absorption bases, contain little or no water and include, for example, hydroxystearic sulfate, anhydrous lanolin, hydrophilic petrolatum, and the like, as well as mixtures thereof. Emulsion cosmetic bases can include water-in-oil (W/O) emulsions, or oil-in-water (O/W) emulsions, such as, e.g., cetyl alcohol, lanolin, glyceryl monostearate, stearic acid, and the like, as well as mixtures thereof. Useful water-soluble ointment bases can be those prepared from glycol ethers such as, for example, polyethylene glycols of varying molecular weight, polysorbates, and the like, as well as mixtures thereof. Petrolatum may be at a concentration of greater than or equal to 50%, preferably greater than or equal to 70%, for example.

Yet other examples of carriers include edible carriers or food additives. Nonlimiting examples of edible carriers and food additives include proteins (e.g., whey), cereal grains (e.g., wheat flour, oat flour, barley flour, rye flour, and the like), edible seed or plant meal (e.g., coconut flour, rice flour, com starch, com flour, potato flour, and the like), starches (e.g., com starch, potato starch, and the like), sugars and carbohydrates (e.g., dextrose, fructose, glucose, hydrolyzed cornstarch, lactose, maltodextrin, maltose, sucrose, starch, and the like), fatty acids, fillers (e.g., psyillium, cellulose, polydextrose, and the like), edible oils (e.g., coconut oil, soy bean oil, sunflower oil, vegetable oil, and the like), and the like, as well as combinations thereof. The carrier can have any useful form, such as a water-in-oil emulsion, cream, liquid, gel, oil, paste, ointment, suspension, foam, lotion, oil-in-water emulsion, water-in- oil-in-water emulsion, water-in-silicone emulsion, powders, and the like.

The carrier can include one or more excipients. Excipients include but are not limited to natural oils, synthetic oils, emulsifiers, emollients (e.g., any described herein), enhancers, lipids, occlusives, humectants, moisturizers, binders, conditioning agents, emulsion stabilizing salts, preservatives, chelating agents, sequestering agents, abrasives, pH adjusters, surfactants, perfumes, flavors, thickening agents, stabilizers, defoaming agents, pigments, and coloring agents.

Emollients

An emollient (or moisturizer) can be added to the composition. Without wishing to be limited by mechanism, an emollient can be employed to break the dry skin cycle and/or to maintain the smoothness of skin.

Non-limiting emollients include a carboxamidine, a hydrocarbon (e.g., a polyunsaturated hydrocarbon), an alcohol (e.g., an aliphatic alcohol, including aliphatic diols, triols, and the like), an amphiphile, a farnesene derivative, a farnesene dimer, a farnesane dimer, an oil, and the like (e.g., such as ectoine, hydroxyectoine, dihydrofarnesene, tetrahydrofarnesene, hexahydrofarnesene, hexahydrofarnesol, hexahydrofarnesyl ethanoate, hexahydrofarnesyl hexahydrofarnesoate, hemisqualane (or farnesane), isosqualane, isosqualene, neosqualane, squalane, squalene, glycerin, lecithin, tricaprylin, capryl ic/capric/lauric triglycerides, sesame seed oil, castor seed oil, apricot kernel oil, olive fruit oil, jojoba seed oil, and the like). Yet other emollients can include one or more occlusive (e.g., lanolin, liquid paraffin, mineral oil, petroleum jelly, and the like), humectants (e.g., glycerin, hyaluronic acid, propylene glycol, or urea), and the like.

In some embodiments, a farnesene dimer includes a compound having the following formula:

well as stereoisomers thereof or a mixture of stereoisomers thereof.

In some embodiments, a farnesane dimer includes a compound having the following formula: , well as stereoisomers thereof or a mixture of stereoisomers thereof.

Further examples of compounds (e.g., including but not limited to farnesene derivatives, farnesene dimers, farnesane dimers, and the like) are described in U.S. Pat. No. 10,695,273, which is incorporated herein by reference in its entirety.

In some embodiments, the emollient is selected to provide increased skin hydration due to skin surface occlusions. In other embodiments, the emollient is configured for deep absorption into the skin, thereby acting as a normalizer for flexibility and suppleness of the skin without presenting an oily residue. In yet other embodiments, the emollient can be selected to provide beneficial penetration or diffusion of one or more compounds from the composition and into the skin.

The emollient can be present in any useful amount. In some embodiments, the emollient is present in an amount from about 0.05% to 30% (v/v) (e.g., from about 0.05% to 1 % (v/v), 0.05% to 5% (v/v), 0.05% to 10% (v/v), 0.05% to 15% (v/v), 0.05% to 20% (v/v), 0.05% to 25% (v/v), 0.1% to 1 % (v/v), 0.1% to 5% (v/v), 0.1% to 10% (v/v), 0.1% to 15% (v/v), 0.1% to 20% (v/v), 0.1% to 25% (v/v), 0.1% to 30% (v/v), 0.5% to 1 % (v/v), 0.5% to 5% (v/v), 0.5% to 10% (v/v), 0.5% to 15% (v/v), 0.5% to 20% (v/v), 0.5% to 25% (v/v), 0.5% to 30% (v/v), 1% to 10% (v/v), 1% to 15% (v/v), 1% to 20% (v/v), 1% to 25% (v/v), 1% to 30% (v/v), 2% to 10% (v/v), 2% to 15% (v/v), 2% to 20% (v/v), 2% to 25% (v/v), 2% to 30% (v/v), 5% to 10% (v/v), 5% to 15% (v/v), 5% to 20% (v/v), 5% to 25% (v/v), 5% to 30% (v/v), 10% to 15% (v/v), 10% to 20% (v/v), 10% to 25% (v/v), 10% to 30% (v/v), 15% to 20% (v/v), 15% to 25% (v/v), 15% to 30% (v/v), 15% to 35% (v/v), 15% to 40% (v/v), 20% to 25% (v/v), 20% to 30% (v/v), or 25% to 30% (v/v)).

Active compounds

One or more active compounds can be employed in the composition. In particular embodiments, the active compound is a cosmetic agent or a cosmeceutical agent. In further embodiments, the active compound can be configured for dermal or topical delivery to skin. In other embodiments, the active compound is an edible agent. In yet other embodiments, the active compound can be configured for oral delivery.

Examples of the cosmetically active agents include vitamins, such as vitamin B, vitamin C, tocopherols (vitamin E), tocopherol derivatives, tocotrienols, vitamin D, K and derivatives thereof, and suitable combinations thereof, for example.

Active compounds may include one or more moisturizing compounds, such as glycerin, urea, methylurea, ethylurea, allantoin, lactates, sugars, methyl glucose ethers, sodium pyrrolidone carboxylic acid, sodium hyaluronate, panthenol, hyaluronic acid, a- and [3-hydroxyl acids, such as glycolic acid, lactic acid, mandelic acid, or salicylic acid, or combinations of the suitable moisturizing compounds, for example.

Compositions may further comprise a penetration enhancer, such as tissue penetration enhancers, to enhance release and delivery of the active compound into tissues, such as, for example, skin, ocular, nasal. For these compositions, they might comprise both active agents and tissue penetration enhancers. The tissue penetration enhancers may then enhance tissue absorption and penetration of the released active agent. The tissue penetration enhancers might be either in suspended solid or solubilized form in the compositions.

Tissue penetration enhancers, such as suitable volatile organic solvents, include aliphatic, cycloaliphatic and/or aromatic-aliphatic alcohols, each of which is monohydric or polyhydric, alcohol/water mixtures, saturated and/or unsaturated fatty alcohols which each contains from about 8 to about 18 carbon atoms, saturated and/or unsaturated fatty acids which each contains from about 8 to about 18 carbon atoms and/or esters thereof and the like and mixtures thereof. Useful alcohols are those having from 1 to about 20 carbon atoms, e.g., ethanol, isopropyl alcohol, 1-butanol, 1-octanol, etc.

Examples of edible agents include micronutrients, vitamins, minerals, trace elements, or combinations thereof, such as vitamin A, vitamin B1 , vitamin B2, vitamin B3, vitamin B5, vitamin B6, vitamin B7, vitamin B12, vitamin A, vitamin C, vitamin D, vitamin E, vitamin H, vitamin K, folic acid, inositol, nicotinic acid, calcium (Ca), phosphorus (P), magnesium (Mg), sodium (Na), potassium (K), chloride (Cl), sulfur (S), iron (Fe), manganese (Mn), copper (Cu), zinc (Zn), iodine (I), selenium (Se), fluorine (F), chromium (Cr), or a combination of any of these.

The one or more active compounds can be selected from the group consisting of one or more of an emulsifier, emollient, preservative, brightening agent, anti-aging agent, anti-inflammatory agent, antioxidant agent, antimicrobial agent, revitalizing agent, smoothing agent, detoxifying agent, hydrating agent, colorant agent, fragrance agent, masking agent, UV- and blue light-protecting agent, anti-pollution agent, proteins, peptide, vitamin, cannabinoid, alpha-hydroxy acid, amino acid, polyphenol, catechin, essential oil, mineral, fatty acid, glycosaminoglycan, prebiotic agent, probiotic agent, postbiotic agent, and symbiotic agent. In particular embodiments, the active compound for cosmetic application is selected from an anti-aging agent (e.g., niacinamide), an antiinflammatory agent (e.g., 2 -fucosy I lactose (2FL), cannabidiol (CBD), cannabinol (CBN), or cannabigerol (CBG)), an antioxidant, an antimicrobial agent (e.g., protocatechuic acid (PCA), cannabichromene (CBC), and the like), which can be added as single molecule or as a combination of molecules to the composition. Other non-limiting active compounds include a vitamin (e.g., ascorbic acid, a- carotene, [3-carotene, niacin, niacinamide, nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), tetrahexyldecyl ascorbate, ascorbyl palmitate, pantothenic acid, retinoic acid, retinoid, retinol, bakuchiol, tocopherol, tocotrienol, tocopheryl acetate, tretinoin, vitamin C, farnesylated vitamin C conjugate, vitamin D, vitamin D2, vitamin D3, vitamin K, and the like); a saccharide (e.g., 2 -fucosy I lactose (2FL), lactose, fucose, and the like); a cannabinoid (e.g., cannabidiol (CBD), cannabidiolic acid (CBDA), cannabinol (CBN), cannabigerol (CBG), cannabigerolic acid (CBGA), cannabichromene (CBC), cannabicyclol (CBL), cannabivarin (CBV), tetrahydrocannabivarin (THCV), cannabidivarin (CBDV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), cannabigerol monomethyl ether (CBGM), cannabielsoin (CBE), cannabicitran (CBT), tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), and the like); a hydroxybenzoic acid (e.g., protocatechuic acid (PCA), gallic acid, p-hydroxybenzoic acid (HBA), and the like), a polyphenol (e.g., resveratrol, quercetin, curcumin, epigallocatechin-3-gallate, resveratrol, cyanidin, and the like), a protein (e.g., lactoferrin), a peptide (e.g., yeast extracts), as well as other compounds such as caffeine, ectoine, beta caryophyllene, bisabolol, as well as derivatives thereof.

The active agent can be present in any useful amount. In some embodiments, the active agent is present in an amount from about 0.1% to 20% (v/v) or (w/w) (e.g., from about 0.1 % to 0.5% (v/v) or (w/w), 0.1 % to 1 % (v/v) or (w/w), 0.1 % to 5% (v/v) or (w/w), 0.1 % to 10% (v/v) or (w/w), 0.1 % to 15% (v/v) or (w/w), 0.1 % to 20% (v/v) or (w/w), 0.5% to 1 % (v/v) or (w/w), 0.5% to 5% (v/v) or (w/w), 0.5% to 10% (v/v) or (w/w), 0.5% to 15% (v/v) or (w/w), 0.5% to 20% (v/v) or (w/w), 1 % to 10% (v/v) or (w/w), 1% to 15% (v/v) or (w/w), 1 % to 20% (v/v) or (w/w), 2% to 10% (v/v) or (w/w), 2% to 15% (v/v) or (w/w), 2% to 20% (v/v) or (w/w), 5% to 10% (v/v) or (w/w), 5% to 15% (v/v) or (w/w), 5% to 20% (v/v) or (w/w), 10% to 15% (v/v) or (w/w), 10% to 20% (v/v) or (w/w), or 15% to 20% (v/v) or (w/w)). In some embodiments, the amount can be determined based on the volume of the active agent and the volume of the carrier or other material. In other embodiments, the amount can be determined based on the weight of the active agent and the weight of the carrier or other material. Other compounds (e.g., active compounds, emollients, emulsifiers, and the like) are described in U.S. Pat Nos. 10,695,273 and 11 ,219,586, each of which is incorporated herein by reference in its entirety.

Uses

The present disclosure encompasses various uses of CMH, as well as uses of compositions including CMH. In one embodiment, the composition is a personal care product, such as a cosmetic or cosmetic product. In some embodiments, CMH can be provided within a personal care product. In other embodiments, CMH can be provided in a composition that is adapted for admixture with a personal care product.

In some embodiments, a personal care product refers to a substance in any suitable form, such as liquid, suspension, semi-liquid, cream, lotion, semi-sold, solid, impregnated substrate, or the like that can be topically applied to a subject (e.g., skin, hair, or nails) or orally applied to a subject (e.g., teeth or mucous membranes of the oral cavity). In another embodiment, the composition is a food additive comprising CMH. In particular embodiments, a food additive refers to a substance in any suitable form, such as liquid, suspension, semi-liquid, semi-sold, solid, impregnated substrate, or the like that can be orally delivered to a subject. As used herein, “subject” is an organism that is tested with one or more compositions of the present disclosure. In some embodiments, the subject is a mammalian subject, such as a human or a domestic animal.

Within a composition, the CMH can be present in any useful amount. In some embodiments, the CMH is present in an effective amount. As used herein an “effective amount” means an amount necessary to at least partly attain the desired response, or to delay the onset or inhibit progression or halt altogether, the onset or progression of a particular symptom being treated. The amount varies depending upon the health and physical condition of the subject to be treated, the taxonomic group of subject to be treated, the degree of protection desired, the formulation of the composition, the assessment of the medical situation, and other relevant factors. It is expected that the amount will fall in a relatively broad range that can be determined through routine trials.

The compositions can be administered or applied in a variety of unit dosage forms depending upon the method of administration or application. The compositions and cosmetics provided herein may be applied to any available skin area that is in need of treatment. In some embodiments, the composition or cosmetic is applied to the skin area liberally such that the skin area is saturated with the composition or cosmetic. In other embodiments, a specific amount of the composition or cosmetic can be applied to a specific amount of skin area (for example 1 mg composition per 1 cm ² skin area and the like). The compositions and cosmetics may be applied as needed to ameliorate the condition or symptom being treated. In embodiments, the compositions and cosmetics are applied at least once daily, at least twice daily, or as needed.

The compositions and food additives provided herein may be consumed as needed. In some embodiments, a specific amount of the composition or food additive can be consumed to provide a specific dietary amount (e.g., an amount within a Recommended Dietary Allowance (RDA)). The compositions and food additives may be consumed as needed to ameliorate the condition or symptom being treated. In embodiments, the compositions and food additives are consumed at least once daily, at least twice daily, or as needed.

As used herein, the term "comprising" whenever used in this document is intended to indicate the presence of stated features, integers, steps, components, but not to preclude the presence or addition of one or more other features, integers, steps, components or groups thereof.

The foregoing disclosure should not be seen in any way restricted to the embodiments described and a person with ordinary skill in the art will foresee many possibilities to modifications thereof.

The embodiments described above are combinable.