CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Application No.

63/016,180, filed April 27, 2020, and entitled “Naturally Based Preservatives for Personal Care Applications,” which is incorporated by referenced herein in its entirety

FIELD OF THE INVENTION

[0002] The present invention relates to naturally based preservatives. More specifically the present invention relates to a composition comprising an alkyl mannoside and its use as a preservative in personal care products. Alkyl mannosides may be used to reduce or prevent the growth of microorganisms in personal care products.

BACKGROUND OF THE INVENTION

[0003] There is growing demand for new and useful naturally based ingredients useful in personal care and cosmetic applications. Consumers are demanding, and companies are looking for, ingredients to replace synthetic or petroleum-based components in personal care formulations. Finding such replacements can be difficult because the existing ingredients are well known, highly functional, and cost effective. Preservatives are one such family of ingredients. Most personal care products contain one or more ingredients specifically designed to maintain the self- life of the products by preventing or slowing the growth of microorganisms such as bacteria or fungi. Because most personal care items are utilized by the consumer over an extended period of time, they must be stable through the duration of the intended period of use. Accordingly, many synthetic, chemical, or petroleum-based products are known for use as preservatives in this field. There exists a need for new naturally based or sourced alternatives for these products.

SUMMARY OF THE INVENTION

[0004] In a first aspect, the present invention relates a natural preservative system for personal care products comprising an alkyl mannoside wherein the alkyl group is a C6-C22 linear, branched, or cyclic alkyl chain or a mixture thereof. The alkyl mannoside may be or comprise octyl mannoside, e.g., n-octyl mannoside. The natural preservative system may also comprise an antifungal agent, for example, an antifungal agent selected from the group consisting of benzoic acid, sorbic acid, salicylic acid, caprylhydroxamic acid, propanediol, undecylenic acid, caprylic acid, and combinations thereof.

[0005] An additional aspect of the present invention is a personal care or cosmetic product containing between 0.1 and 5% by weight of an alkyl mannoside wherein the alkyl group is a C6-C22 linear, branched, or cyclic alkyl chain. The alkyl mannoside may be present in the personal care or cosmetic product at a concentration of 0.01% to 3%, 0.1% to 2%, 0.5% to 10%, or 1% to 3% by weight. The alkyl mannosdie may be or comprise octyl mannoside. The octyl mannoside may be present in the personal care or cosmetic product at a concentration of 0.1% to 5%, 0.01% to 3%, 0.1% to 2%, 0.5% to 10%, or 1% to 3% by weight. The product may additionally comprise a natural or synthetic preservative, for example, an antifungal agent. The personal care or cosmetic produce may comprise 0.01% to 5%, 0.01% to 3%, 0.1% to 2%, 0.5% to 10% by weight of an antifungal agent; 0.01% to 5%, 0.01% to 3%, 0.1% to 2%, 0.5% to 10% by weight of an antifungal agent selected from the group consisting of benzoic acid, sorbic acid, salicylic acid, caprylhydroxamic acid, propanediol, undecylenic acid, caprylic acid, and combinations thereof; 0.01% to 5%, 0.01% to 3%, 0.1% to 2%, 0.5% to 10% by weight of a composition comprising 7-8% by weight caprylhydroxamic acid and 92-93% by weight propanediol, e.g., ZEASTAT; or 0.01% to 5%, 0.01% to 3%, 0.1% to 2%, 0.5% to 10% by weight of a composition comprising 85-91% by weight phenoxyethanol and 9-15% by weight ethylhexylglycerin, e.g., ISCAGUARD PEHG.

[0006] In an additional aspect, the personal care product can be a cosmetic, skin cream, lotion, sunscreen, skin cleanser, or skin conditioner.

[0007] A further aspect is a method of using, or the use of, an alkyl mannoside wherein the alkyl group is a C6-C22 linear, branched, or cyclic chain or a mixture thereof in a personal care or cosmetic product. The personal care product can be a cosmetic, skin cream, lotion, sunscreen, skin cleanser, or skin conditioner.

BRIEF DESCRIPTION OF THE DRAWINGS [0008] FIG. 1 shows a graph of Staphylococcus aureus, Pseudomonas aeruginosa,

Escherichia coli, Candida albicans, and Aspergillus brasiliensis contamination rate in face serum formulations containing 0.5033 w/w % n-octyl mannoside.

[0009] FIG. 2 shows a graph of Staphylococcus aureus, Pseudomonas aeruginosa,

Escherichia coli, Candida albicans, and Aspergillus brasiliensis contamination rate in face serum formulations containing 0.2505 w/w % n-octyl mannoside. [0010] FIG. 3 shows a graph of Staphylococcus aureus, Pseudomonas aeruginosa,

Escherichia coli, Candida albicans, and Aspergillus brasiliensis contamination rate in face serum formulations containing 0.0253 w/w % n-octyl mannoside.

[0011] FIG. 4 shows a graph of Staphylococcus aureus, Pseudomonas aeruginosa,

Escherichia coli, Candida albicans, and Aspergillus brasiliensis contamination rate in face serum formulations containing 0.25 w/w % n-octyl mannoside as described in Example 2.

[0012] FIG. 5 shows a graph of Staphylococcus aureus, Pseudomonas aeruginosa,

Escherichia coli, Candida albicans, and Aspergillus brasiliensis contamination rate in face serum formulations containing 0.25 w/w % n-octyl mannoside and 0.50 w/w %

ISCAGUARD ^® PEHG preservative (85-91% phenoxyethanol and 9-15% ethylhexylglycerine). [0013] FIG. 6 shows a graph of Staphylococcus aureus, Pseudomonas aeruginosa,

Escherichia coli, Candida albicans, and Aspergillus brasiliensis contamination rate in face serum formulations containing 0.25 w/w % n-octyl mannoside and 0.25 w/w % of ZEASTAT preservative (7-8 % caprylhydroxamic acid and propanediol).

[0014] FIG. 7 shows a graph of Staphylococcus aureus, Pseudomonas aeruginosa,

Escherichia coli, Candida albicans, and Aspergillus brasiliensis contamination rate in face serum formulations containing 1% GEOGARD ECT preservative (benzyl alcohol, salicylic acid, glycerin, and sorbic acid).

DETAILED DESCRIPTION

[0015] The use of “a” or “an” to describe the various elements or components herein is merely for convenience and to give a general sense of the invention. This description should be read to include one or at least one, and the singular also includes the plural unless it is obvious that it is meant otherwise.

[0016] The invention is defined in the appended claims. At least one aspect of the invention is based on the finding that the alkyl mannosides disclosed herein can act as a preservative to prevent the growth of microorganism in personal care products.

[0017] The present invention further relates to the use of the alkyl mannoside composition to prepare a cosmetic or personal care composition.

[0018] The present invention further relates to the use of the alkyl mannoside as a preservative in a cosmetic or personal care composition. [0019] An advantage of using the alkyl mannoside composition of the present invention is that it can be readily formulated, and thus is very suitable for use in many applications, such as for example a cream or lotion.

[0020] In one aspect, the present invention is a topical formulation comprising an alkyl mannoside composition described herein. As used herein, the term “topical formulation” refers to a formulation that may be applied directly to a part of the body. The term “formulation” is used herein to denote compositions of various ingredients in various weight ranges, in accordance with the present invention. Such compositions are well known in the art to the skilled person.

[0021] The formulations manufactured with the alkyl mannoside composition described herein are suitable for use on hair, scalp, nails, and skin, for delivering cosmetic or actives to the skin or hair for providing cleansing, conditioning, moisturizing, minimizing or treating skin imperfections, reducing skin oiliness, providing fragrances to the hair or skin and the like.

[0022] “Personal care” means and comprises any, cosmetic, hygienic, toiletry, and topical care products including, without limitation, leave-on products (i.e., products that are left on the skin or keratinous substrates after application); rinse-off products (i.e., products that are washed or rinsed from the skin or keratinous substrates during or within a few minutes of application); shampoos; hair curling and hair straightening products; hair style maintaining and hair conditioning products; lotions and creams for nails, hands, feet, face, scalp and/or body; hair dye; face and body makeup; nail care products; astringents; deodorants; antiperspirants; anti-acne; antiaging; depilatories; colognes and perfumes; skin protective creams and lotions (such as sunscreens); moisturizers; skin and body cleansers; skin conditioners; skin toners; skin firming compositions; skin tanning and lightening compositions; liquid soaps; bar soaps; bath products; shaving products; and oral hygiene products (such as toothpastes, oral suspensions, and mouth care products). Preferably the personal care product may comprise from 0.01 to 5 wt%, preferably from 0.01 to 5 wt%, more preferably from 1 to 3 wt%, even more preferably from 1 to 2 wt% of the alkyl mannoside composition, based on the weight of the personal care product. The personal care product may comprise 0.01% to 5%, 0.01% to 3%, 0.1% to 2%,

0.5% to 10%, or 1% to 3% by weight of the alkyl mannoside. The personal care product may comprise 0.01% to 5%, 0.01% to 3%, 0.1% to 2%, 0.5% to 10%, or 1% to 3% by weight of octyl mannoside. The present invention also relates to the use of the alkyl mannoside composition in personal care products. [0023] The texture of such personal care formulations is not limited and may be, without limitation, a liquid, gel, spray, emulsion (such as lotions and creams), shampoo, pomade, foam, tablet, stick (such as lip care products), makeup, suppositories, among others, any of which can be applied to the skin or hair or nail and which typically are designed to remain in contact therewith until removed, such as by rinsing with water or washing with shampoo or soap. Other forms could be gels that can be soft, stiff, or squeezable. Sprays can be non-pressurized aerosols delivered from manually pumped finger-actuated sprayers or can be pressurized aerosols such as mousse, spray, or foam forming formulation, where a chemical or gaseous propellant is used.

[0024] The personal care formulation comprising the alkyl mannosides disclosed herein may be a cream or lotion that may optionally include sun blocking agents, moisturizers, or other active ingredients.

[0025] The personal care formulation may be a cosmetic product. Cosmetic products can be make-up creams, make-up lotions, lipsticks, powders, foundations, highlighters, eye liners, eye shadow, colorants, moisturizers, perfumes, and the like. Preferably the cosmetic product may comprise from 0.01 to 5 wt%, preferably from 0.01 to 3 wt%, more preferably from 1 to 2 wt%, even more preferably from 5 to 10 wt% of the present alkyl mannoside composition, based on the weight of the cosmetic product. The cosmetic product may comprise from 0.01 to 5 wt%, preferably from 0.01 to 3 wt%, more preferably from 1 to 2 wt%, even more preferably from 5 to 10 wt% of the present n-octyl mannoside composition, based on the weight of the cosmetic product The present invention also relates to the use of the alkyl mannoside composition in cosmetic products. In particular, the present invention also relates to the use of the alkyl mannoside composition in cosmetic products.

[0026] In addition to the alkyl mannoside described herein, personal care and cosmetic compositions envisioned herein may also contain additional natural or synthetic ingredients that act as preservatives, biocides, or fungicides. The additional natural or synthetic ingredients may be antifungal agents. As used herein, “antifungal agent” refers to a compound or composition that prevents or slows the growth of fungi in a composition. For example, a mold (e.g., Aspergillus brasiliensis ) or a yeast (e.g., Candida albicans). Suitable antifungal agents are known and described in the art, and my include, but are not limited to, benzoic acid, sorbic acid, salicylic acid, caprylhydroxamic acid, propanediol, undecylenic acid, caprylic acid, and combinations thereof. The antifungal agent may be a combination of caprylhydroxamic acid and propanediol, for example an antifungal sold under the tradename ZAESTAT with 7-8 % by weight caprylhydroxamic acid in propanediol. The antifungal agent may be a combination of phenoxyethanol and ethylhexylglycerin, for example an antifungal sold under the tradename ISCAGUARD PEHG with 85-91% by weight phenoxyethanol and 9-15% ethylhexylglycerin. The antifungal agent may be a combination of benzyl alcohol, salicylic acid, glycerin, and sorbic acid, for example a preservative sold under the tradename GEOGARD ECT. The personal care compositions may from 0.01 to 5 wt%, preferably from 0.01 to 3 wt%, more preferably from 1 to 2 wt%, even more preferably from 5 to 10 wt% of the antifungal agent.

Preparation of Alkyl Mannosides

[0027] The term “Alkyl” as used herein refers to linear, branched, or cyclic saturated alkyl chain having 6-22 carbons. The alkyl mannosides can be prepared by the acid catalysed alcoholysis of mannose with a C6-C22 linear, branched, or cyclic alkanol. The mannose may be D-mannose, L-mannose or a mixture of both. Preferred alkanols include octanol, decanol and dodecanol. The mannose may be a mannose containing composition, isolated mannose, a mannose solution or a mixture of these. The alcohols may be single species or mixture of alcohols which will result in a mixture of mannosides. Preferably the mannose is purified mannose compositions and the alcohol is octanol. The reaction with octanol is described below in Scheme 1.

Scheme 1

[0028] The amount of acidifying catalyst used is preferably in a weight ratio to mannose of mannose: acidifying catalyst 100:0.005 to 100:1, and more preferably from 100:0.1 to 100:0.5.

[0029] Preferably the acidifying catalyst is p-toluenesulphonic acid. [0030] The temperature of the reaction will generally affect the rate and the production of side products. Preferably the temperature of the alcoholysis step a) is from 85°C to 120°C, more preferably 90°C to 110°C, more preferably 95 °C to 100°C.

[0031] The reaction is preferably performed at a reduced pressure to remove any water produced or present in the reaction mixture. The reaction pressure may vary between 50 and 300 millibar based on the addition of reactants and production of water. At too low a pressure alcohol being used in the reaction may be removed from the reaction mixture which is undesirable. Therefore, the temperature and pressure should be maintained to remove water and minimize removal of the relevant alcohol. The reaction may be performed with or without the use of a solvent or co-solvent.

[0032] The reaction time of alcoholysis step is determined by monitoring the reduction in mannose concentration as the reaction proceeds. The reaction is stopped when the mannose is completely or substantially completely consumed.

[0033] The reaction is cooled and neutralized by the addition of a base. Choice of the basis not critical and a skilled person would appreciate different alternatives could for the neutralization. A preferred base is sodium ethoxide. Base may be added to the reaction mixture and pH monitored to achieve a basic pH of 8 or greater.

[0034] The excess reaction alcohol is removed for the product by rotary evaporation or short path distillation to yield a crude product. The crude product can be purified in a number of ways know in the art. For example, the crude product can be loaded onto a silica gel column and eluted with a solvent in one or more passes.

Example 1:

Production of n-octyl mannoside

[0035] n-Octanol (1 Lt) containing p-TsOH (3.18 g, 0.0167 mol, 0.01 eq) was stirred at

100°C under reduced pressure (-150 mbar) for 1 hour, in a globe reactor. Then, a warm (40°C) suspension of D-mannose (300 g, 1.67 mol, 1 eq) in octanol (900 mL) was added to the reaction mixture in 7 portions, every 10 minutes approximately (when reaction mixture became clear) and the mixture was stirred at the same conditions. During reaction, the pressure varied between 50-300 mbar. Approximately 13 mL H20 was removed during reaction, together with 5 mL octanol. Total reaction time, starting from the addition of mannose, was 3 hours. The reaction mixture was allowed to cool to 90°C, basified with -20 mL EtONa (21%wt in EtOH) and stirred for 1 hour to reach pH 9. Then, octanol was removed under reduced pressure (0-40 mbar), at 100-110 °C.

[0036] The resulting residue (730 g) was purified using 1.6 kg Si02 and EtOAc to

EtOAc/MeOH = 10/1, as eluent. Fractions containing the product were combined, evaporated affording 300 g of mixture. This mixture was purified under the same conditions (1.6 kg Si02, EtOAc to EtOAc/MeOH = 10/1). The purity of the fractions containing the product was still not high enough, so they were combined, evaporated and purified for a last time under the same conditions (1.6 kg Si02 and EtOAc to EtOAc/MeOH = 10/1). Two batches of product were obtained: Example 1C, 52.11 g, 95% (NMR), ratio of octyl a: b mannopyranoside = 100:8 and Example ID, 41.21 g, 83.5% purity (NMR), ratio of octyl a: b mannopyranoside = 100:6. Total yield (taking into account purity): 17%.

Table 1.

Evaluation of n-octyl mannoside

[0037] A sample of n-octyl mannoside was evaluated by a third party laboratory for its effect on the growth of a variety of microorganisms. Microorganisms are provided and identified by the American Type Culture Collection (ATCC) accession number. Staphylococcus aureus ATCC* 6538; Pseudomonas aeruginosa ATCC 9027; Escherichia coli ATCC 8739; Candida albicans ATCC 10231; and Aspergillus brasiliensis ATCC 16404.

[0038] Stock suspensions of the cultures are prepared as follows. The suspensions are prepared into working cultures, themselves stemming from mother/starter cultures. From these working cultures and for each bacterium, spectrophotometry calibrations are created to obtain suspensions in values of 1.107 to 1.108 CFU/mL. For Candida albicans, the suspension is between 1.106 to 1.107 CFU/mL. These suspensions are obtained by dispersing colonies in sterile jars containing peptone salt liquid broth and glass beads to allow better homogenization of colonies in the diluent. The concentrations of suspensions are controlled by BIOLUMIX reading incubator at TO with adding of 100 pL of suspension in the appropriate flow cell. The results are obtained after 24 H to 35 H for bacteria and 48 H for yeast and mold.

[0039] The product to be tested is distributed in five sterile jars of 20g or 20mL, each being intended for one of the five strains. The octylmannoside was tested at three different concentrations; i.e., 0.5033%, 0.2505% and 0.0253% w/w in water.

[0040] The five jars including a face serum formulation are separately inoculated with

0.2 mL of each previously prepared inoculum so as to obtain a final concentration between 1.105 and 1.106 CFU/g or mL of bacteria and between 1.104 and 1.105 CFU/g or mL of Candida albicans and Aspergillus brasiliensis . The face serum used in the evaluation was an oil in water emulsion that is stable for over 2 months at ambient temperature in the presence of hyaluronic acid, fragrance, and pigment. Jars are strongly shaken to guarantee a homogeneous distribution of the inoculum in the product. The jars are stored at +22.5°C ± 2.5°C and shielded from the light during fourteen days of the analysis.

[0041] From each of five inoculated jars, 1 g or 1 mL are taken then diluted in 1/lOOe with TSB Capitol 4 liquid broth. The mixture is rested for approximately 30 min ± 15 min at ambient temperature, to complete the neutralization of the preservative system. 1 mL sample from each tube is taken then put down in BIOLUMIX flow cells (“TVC” for bacteria and “DYM” for yeasts and molds). The cells are placed in the BIOLUMIX reading incubators respectively at +35°C for bacteria and +28°C for yeasts and molds. Each flow cell is assigned a barcode according directly to the information of the study.

[0042] Measures are made in BIOLUMIX reading incubators; it is the colorimetric variation of the reading window that is obtained. The compilation of listed data generated growth curves for each reference strains potentially included in the flow cell. The growth curves in comparison with BIOLUMIX calibration curves express a concentration of microorganisms (CFU/g or mL).

[0043] After sampling for contamination by each of five strains, the rate of logarithmic reduction (Rx) is calculated and compared with the values required for the evaluation of Criteria

A and Criteria B. Meeting the values required for Criteria A indicates that the formula is protected against microbial proliferation. Meeting the values required for Criteria B indicates that the level of protection is acceptable if the analysis of the risk demonstrates the existence of factors of control not bound to the formulation indicating that the microbiological risk is acceptable for the cosmetic product. The criteria are expressed as either (i) a minimal value of rate of logarithmic reduction; or (ii) by “PA*,” (i.e., no increase) the requirement that there is no increase of the microbial population. If all rates of logarithmic reduction correspond to Criteria A, the formula satisfies the requirements A to the try of efficiency of antimicrobial protection.

If all or part of logarithmic reduction correspond just to criteria B, the formula satisfies the requirements B to the try of efficiency of antimicrobial protection. If one or several of the rates of reduction don’t correspond either to the criteria A or to the criteria B, the formula doesn’t satisfy the requirements to the try of efficiency of the antimicrobial protection.

[0044] The results for n-octyl mannoside are shown in FIGS. 1-3. The testing confirms that n-octyl mannoside is highly effective at controlling the presences of various bacteria down to a concentration of at least 0.25% w/w.

Example 2:

Evaluation of n-octyl mannoside with antifungal

[0045] Formulations of n-octyl mannoside with and without an antifungal agent were evaluated using the same methods and criteria outlined in Example 1. The face serums tested in this Example are oil-in-water emulsions but do not include hyaluronic acid, fragrance, and pigment. The tested face serum in combination with the antimicrobial formulations were stable for 2 months (entire length of study) at ambient temperature, 4 °C, and 45 °C (data not shown). Antimicrobial formulations tested include (i) 0.50 w/w % n-octyl mannoside; (ii) 0.50 w/w % n- octyl mannoside with 0.50 w/w% ISCAGUARD ^® PEHG (90% phenoxyethanol and 10% ethylhexylglycerine); (iii) 0.50 w/w% n-octyl mannoside with 0.25 w/w% ZEASTAT (caprylhydroxamic acid and propanediol); (iv) and 1% GEOGARD ECT as a positive control. Results of the evaluation are outlined FIGS. 4-7. The testing confirms that n-octyl mannoside in combination with an antifungal agent such as ISCAGUARD PEHG preservative or ZEASTAT preservative is effective at controlling the presences of various bacteria and fungi in face serum compositions.