WO2024028271A1

WO2024028271A1 - Antimicrobial composition for cosmetic formulations

Info

Publication number: WO2024028271A1
Application number: PCT/EP2023/071162
Authority: WO
Inventors: Federica CARLOMAGNO; Antonio CRIMALDI; Arianna FILIPPINI; Rosella MALANCHIN
Original assignee: ROELMI HPC SRL
Current assignee: ROELMI HPC SRL
Priority date: 2022-08-04
Filing date: 2023-07-31
Publication date: 2024-02-08
Anticipated expiration: 2025-02-04
Also published as: IT202200016731A1

Abstract

The invention relates to an antimicrobial composition for cosmetic use based on dehydroabietic acid, methods for the preparation thereof, and cosmetic products containing said composition.

Description

ANTIMICROBIAL COMPOSITION FOR COSMETIC FORMULATIONS

Field of the invention

The present invention relates to an antimicrobial composition for cosmetic use comprising dehydroabietic acid, processes for the preparation thereof, and cosmetic products containing said composition.

Background to the invention

Cosmetic products in general, and topical cosmetics in particular, are liable to microbial contamination, due to their use in a non-sterile environment and to contact with the skin. For this reason, their formulations often include compounds with antimicrobial activity which prevent contamination by substances potentially unsafe for use, and maintain the integrity of the products throughout their shelf life.

Ideally, an antimicrobial compound used in a preservative composition has antimicrobial activity against a broad spectrum of organisms including, for example, grampositive and gram-negative bacteria, fungi, moulds, yeasts and protozoa, and maintains said activity throughout the lifetime of the product. It should also be environmentally safe and free of toxic effects for the user at the doses at which it is formulated in the finished product.

In Europe, Annex V of Regulation 1223/2009 lists the substances which can be used as preservatives, in the amounts tested and guaranteed by said Regulation.

Sodium benzoate, benzyl alcohol, 2-phenylethyl alcohol and phenol (at low levels) are among the preservative compounds which are most commonly used and have a good safety profile. However, they only exhibit antimicrobial effects at high concentrations or at a certain pH, and even under said conditions are not always effective against all microbes, in particular spores, fungi, moulds, protozoa and yeasts.

There is consequently a need to identify novel, safe antimicrobial compositions with increased efficacy, in particular against moulds, for use in cosmetic products.

Rosin, a plant resin obtained from conifers, is known to possess some antimicrobial functions. It consists of a mixture of polycyclic hydrocarbons with various degrees of unsaturation and functionality, but all with at least one carboxyl functional group. Said organic acids typically possess a macrocyclic structure consisting of 20 carbon atoms, and can be classified as diterpene species. Despite having said carboxyl functional group, most of the constituents of resin acids are considered to be insoluble in water at a physiological and acid pH (< 7). Only dehydroabietic acid (DHAA) possesses significant solubility under said conditions. One of the challenges involved in using resin acids in such applications is therefore their low solubility in water.

W02019220011 Al discloses an antimicrobial composition consisting of mixtures of conifer resin acids (rosin acids), including DHAA, with an alcohol-based solvent or water as primary solvent, together with a co-solvent (or second solvent) consisting of glycol ethers. Said compositions are water-soluble, can be used as preservatives in a preservative formulation or concentrate which can be added to formulations subsequently, and are suitable for use in the cosmetics field.

W02013060936A1 discloses that a combination of an abietic acid and a dispersing agent can be formulated in an antimicrobial formulation with water. In particular, it discloses that DHAA, either alone or combined with other rosin acids, can be dispersed in water using known dispersing agents for cosmetic and pharmaceutical products, including polyhydroxylated compounds derived from glycol.

WO2016116668A1 discloses an oil-in-water dispersion with antimicrobial properties using rosin acids, including DHAA, which is suitable for cosmetic use.

J. Oleo Ski, 2019; 68(8): 759-763 describes the antibacterial activity of 1,2- alkanediols against Staphylococcus aureus and Staphylococcus epidermidis.

WO20 19090098 Al discloses that 1,2-alkanediols, including caprylyl glycol (octane- 1,2-diol), enhance the activity of known antimicrobial agents, especially organic acids or salts thereof. The resulting antimicrobial compositions can be used as preservatives in cosmetic products. Description of the invention

The subject of the present invention is a mixture of DHAA and 1,2-octanediol (caprylyl glycol) which is useful for antimicrobial protection in cosmetic formulations having various applications.

The caprylyl glycol can be produced synthetically or purified from both renewable or nonrenewable natural sources.

DHAA can be used in the form of a pure substance obtained by known synthesis procedures, such as the one described in J. Am. Chem. Soc. 1962, 84, 2, 284-292, or in the form of a substance isolated from a natural source, or in a mixture with other conifer resin acids of which it constitutes at least 90% by weight, preferably at least 95% by weight.

In a preferred embodiment, the mixture of conifer resin acids having a DHAA content of at least 90% by weight is obtained by a process comprising the following steps: a) distilling crude conifer tall oil to give a resin fraction having an abietic acid content of at least 90% by weight; b) heating said resin fraction to 250-300°C in an inert atmosphere in the presence of a catalyst suitable to convert abietic acid to DHAA; c) cooling the reaction mixture obtained in step b) to 50-70°C, then adding a mixture of organic solvents able to solubilise the residual abietic acid, and filtering to eliminate the catalyst; d) heating the filtrate obtained in step c) to 150-180°C, followed by cooling to 0- 8°C to give a precipitate; e) isolating said precipitate to give a mixture of resin acids wherein the DHAA content is at least 90% by weight.

In one embodiment of the invention, said conifer belongs to the genus Pinus, and is preferably Pinus lambertiana.

In specific embodiments of the invention, the crude tall oil used in step a) is obtained as a by-product of pine wood pulping using the Kraft process.

In a preferred embodiment, step b) is conducted for a time of 2-3 h, preferably 1.5 h, at 290°C in a nitrogen atmosphere. The catalyst employed is preferably palladium on carbon (Pd/C), used in amounts of 0.3-0.5% w/w of said resin fraction.

A mixture of ethyl acetate: methanol at the ratio of 92-95:5-8 v/v is preferably used in step c). The use of said mixture dissolves any abietic acid residues present.

In a further preferred embodiment, the heating described in step c) is conducted for a time of 0.5-1 h.

The mixture of resin acids obtained in step e) typically contains the isomers of DHAA and laevopimaric acid in addition to DHAA.

In preferred embodiments of the invention, the amounts of (i) DHAA or a mixture of conifer resin acids containing at least 90% by weight of DHAA, and (ii) 1,2-octanediol range from 10 to 25% and 75 to 90% respectively of the total weight of the composition.

Another subject of the invention is a method for preparing the antimicrobial composition according to the invention, comprising the following steps:

(i) adding DHAA, or a mixture of conifer resin acids containing at least 90%, preferably at least 95%, of DHAA to 1,2-octanediol under constant stirring at a temperature ranging from 50 to 60°C, until the DHAA or said mixture of resin acids has completely dissolved;

(ii) leaving the solution to cool to room temperature.

The composition according to the invention exhibits antimicrobial effects against: gram-positive bacteria such as S. aureus,' gram-negative bacteria such as /< aeruginosa and E. coir, yeasts such as C. albicans,' and moulds such as A. brasiliensis. The effects of the composition are synergistic, unlike the antimicrobial effects of DHAA and 1,2-octanediol used individually.

The antimicrobial composition according to the invention is therefore useful as a preservative in cosmetic products, in particular those designed for dermatological applications, such as body oil, conditioner, face cleanser, face illuminator, face primer and face serum, body and face emulsions and in particular creams, anhydrous systems, hair conditioning agents and hair masks. A further subject of the invention is therefore a cosmetic product containing the antimicrobial composition according to the invention. Typically, the antimicrobial composition according to the invention is used in amounts ranging from 0.5 to 3% of the total weight of the cosmetic product.

The invention will now be further illustrated by the following examples.

Examples

Example 1 - Preparation of mixture of resin acids with a high DHAA content (> 90%)

Pine pulp, which is a by-product of paper manufacture (Kraft process), mainly consists of hemicellulose, lignin and crude tall oil. In the Kraft process, treatment with concentrated NaOH at high temperature converts the esters and carboxylic acids in the pine pulp to soluble sodium soaps of lignin, resin and fatty acids. The result is a solution called “black liquor” containing about 15% dry matter, which is then concentrated in an evaporator. As the concentration increases, the soaps begin to rise to the surface, from which they are removed and collected by scraping, to obtain “crude resin soap” or “resinate”. Said crude product, purified of the black liquor residue by sedimentation or centrifugation, is then heated and acidified with H2SO4 to produce crude tall oil (CTO). The CTO is fed into a distillation column wherein the different fractions are separated by applying a vacuum (ranging from 3 to 30 mbars) and high temperatures (170 to 290°C); fractionation of a tonne of CTO produces about 350 kg of resin acids (rosin), 300 kg of fatty acids and 350 kg of distilled tall oil. The fractionation takes place according to the different volatilities of the three mixtures of main constituents: the fraction of tall oil resin acids (TOR) is removed at a temperature of about 250-280°C, when the pressure is lower than 10 mbars.

The rosin consists of about 90% abietic acid, while the remaining 10% is a mixture of dihydroabietic acid and dehydroabietic acid.

To obtain dehydroabietic acid with high purity, rosin with a high abietic acid content (> 90%) undergoes an isomerisation reaction at high temperature. The reaction is conducted by heating the reagent at about 290°C for 150 minutes, in a nitrogen atmosphere and in the presence of a catalyst (Pd/C in the amount of 0.3-0.5% by weight of the rosin). At the end of the reaction, the reaction mixture is cooled to about 50-70°C, and an extraction solvent is added to dissolve the unreacted abietic acid residue completely. The extraction solvent is preferably a mixture of ethyl acetate and methanol, with an ethyl acetate to methanol volume ratio of 92-95:5-8. After addition of the solvent, the reaction mixture is filtered under heating to remove the catalyst. As dissolution of the abietic acid residue is promoted by high temperatures, the mixture is then heated again at about 150- 180°C for 30-60 minutes at reflux. In a subsequent step, the mixture is cooled to about 0- 8°C to promote the formation of dehydroabietic acid crystals of high purity, which are separated from the mother liquor by filtration, and washed. The resulting product consists mainly of dehydroabietic acid, with a degree of purity ranging between 90 and 95%.

Example 2 - Preparation of the antimicrobial composition according to the invention

200 g of the mixture obtained according to Example 1 (powder) is added to 800 g of caprylyl glycol under constant stirring, at a temperature of 55 ± 5°C, until the powder has completely dissolved. The resulting solution is left to cool in air to room temperature. The final solution appears as a transparent liquid.

Example 3 - Challenge Test of the antimicrobial composition according to the invention

Before being placed on the market, the cosmetic formulations undergo a challenge test to ensure that the product is protected against microbial contamination which could be hazardous for consumers.

The test involves contaminating the finished cosmetic product, if possible in its final container, with a prescribed inoculum of appropriate micro-organisms (10⁵-l 0⁶ CFU per gram or millilitre of product); storing the inoculated product at a prescribed temperature (20-25°C, protected from light); taking samples from the inoculated products at preset time intervals; and evaluating the variation in microbial load by means of a plate count of the number of live micro-organisms present in the aliquots of product sampled.

The preservative properties of the preparation are appropriate if, under the assay conditions, the number of micro-organisms in the inoculated preparation significantly declines or does not increase.

The acceptance criteria vary for the different types of preparation, according to the degree of protection required: European Pharmacopoeia (Ph. Eur. 5.1.3 curr. ed - Table 5.1.3-1/2/3).

The acceptance criteria for ear preparations, nasal preparations, preparations for cutaneous application and preparations for inhalation (Table 5.1.3-2), listed in Table 1 below, apply to the product in question.

Table 1 - Acceptance criteria

NI = No increase in the number of viable micro-organisms since the previous reading

The A criteria express the recommended efficacy to be achieved. In justified cases where the A criteria cannot be attained, for example for reasons of an increased risk of adverse reactions, the B criteria must be satisfied.

A Challenge Test was conducted on creams A and B, containing two different preservative systems: capryly glycol only (Cream A), and the mixture obtained in Example 2 (Cream B). The compositions of creams A and B are set out in Tables 2 and 3. Table 2 - Composition of Cream A

Table 3 - Composition of Cream B

The results are set out in Tables 4 and 5. Table 4 - Challenge Tes+:t Cream A

Table 5 - Challenge Test: Cream B

Cream A meets the A criteria of the test, but with a slow reduction in mould (Aspergillus brasiliensis): Cream B, containing the antimicrobial composition according to the invention, meets the A criteria of the test and exhibits a rapid reduction in mould (Aspergillus brasiliensis), which eliminates the microbial load after only 7 days.

Example 4 - Cosmetic formulation

Body oil

MANUFACTURING METHOD:

1. Mix the ingredients of Phase A one at a time, at room temperature.

Example 5 - Cosmetic formulation

Face cleansing balm

MANUFACTURING METHOD:

1. Weigh the ingredients of Phase A and heat to 60 ± 2°C;

2. When Phase A is liquid, add the ingredients of Phase B under stirring; 3. Cool rapidly to 30 ± 2°C, then mix for 1 minute.

Example 6 - Cosmetic formulation

Face illuminator

MANUFACTURING METHOD:

1. Weigh the ingredients of Phase A;

2. Weigh the ingredients of Phase B and mix them;

3. Mix Phase A and gradually add Phase B, until the product is homogeneous.

Example 7 - Cosmetic formulation

Face primer

MANUFACTURING METHOD:

1. Weigh the ingredients of Phase A and heat to 90 ± 2°C;

2. When Phase A is liquid, add the ingredients of Phase B under stirring; 3. Cool to 65°C and pour into mould.

Example 8 - Cosmetic formulation

Face serum

MANUFACTURING METHOD:

1. Prepare Phase A at room temperature under stirring;

2. Disperse the ingredients of Phase Al in Phase A with turboemulsifier;

3. Prepare Phase B under stirring;

4. When Phase A + Phase Al is homogeneous, add Phase B and mix for a few minutes at room temperature.

Claims

1. An antimicrobial composition consisting of a mixture of (i) 1,2-octanediol and (ii) dehydroabietic acid alone or as a mixture with other conifer resin acids of which dehydroabietic acid constitutes at least 90% by weight.

2. Composition according to claim 1, wherein said mixture of conifer resin acids has a dehydroabietic acid content of at least 95wt%.

3. Composition according to claims 1-2, wherein said mixture of resin acids containing at least 90% w/w dehydroabietic acid is obtained by the following process: a) distilling crude conifer tall oil to give a resin fraction having an abietic acid content of at least 90wt%; b) heating said resin fraction to 250-300°C in an inert atmosphere and in the presence of a catalyst suitable to convert abietic acid to dehydroabietic acid; c) cooling the reaction mixture obtained in step b) to 50-70°C, then adding a mixture of organic solvents suitable for solubilising the abietic acid residue, and fdtering to remove the catalyst; d) heating the fdtrate obtained in step c) to 150-180°C to promote complete dissolution of the abietic acid residue, followed by cooling to 0-8°C to give a precipitate; e) isolating said precipitate to give a mixture of resin acids wherein the dehydroabietic acid content is at least 90wt%.

4. Composition according to claim 3, wherein said conifer belongs to the genus Pinus, and is preferably Pinus lambertiana.

5. Composition according to claims 3-4 wherein, independently of one another:

(i) the crude tall oil is obtained as a by-product of pine wood pulping using the Kraft process;

(ii) step b) is performed for a time of 2-3 h, preferably 1.5 h, at a temperature

RECTIFIED SHEET (RULE 91) ISA/EP of 290°C;

(iii) the catalyst employed in step b) is palladium on carbon used in the amount of 0.3-0.5w/w of said resin fraction;

(iv) the mixture of organic solvents used in step c) is a mixture of ethyl acetate: methanol at the ratio of 92-95:5-8 v/v;

(v) the heating of step c) is conducted for a time of 0.5-1 h.

6. Composition according to claims 1-5, wherein the amounts of (i) dehydroabietic acid or a mixture of conifer resin acids containing at least 90wt% of dehydroabietic acid and (ii) 1,2-octanediol range from 10 to 25% and from 75 to 90% respectively of the total weight of the composition.

7. Method for preparing a composition according to claims 1-6, which comprises:

(i) adding dehydroabietic acid, or a mixture of conifer resin acids containing at least 90%, preferably at least 95%, of dehydroabietic acid, to 1,2-octanediol under constant stirring at a temperature ranging from 50 to 60°C, until complete dissolution of the dehydroabietic acid or of said mixture of resin acids;

(ii) leaving the solution to cool to room temperature.

8. Cosmetic product containing an antimicrobial composition according to claims 1-6.

9. Cosmetic product according to claim 8, containing said antimicrobial composition in an amount ranging from 0.5% to 3 w/w.

10. Cosmetic product according to claims 8-9, which is a dermatological agent.

11. Cosmetic product according to claims 8-10, which is selected from body oil, face cleansing balm, face illuminator, face primer, face serum, body and face emulsions and in particular creams, anhydrous systems, hair conditioners and hair masks.

RECTIFIED SHEET (RULE 91) ISA/EP