Process for preparing lipid particles

Abstract

The present invention is a lipid particle and a process for producing the lipid particle. The lipid particle comprises a matrix and at least one antioxidant incorporated in the matrix. In one embodiment of the present invention, the lipid particle is used for topical suppression of ROS (reactive oxygen species) in the skin of a patient. In an embodiment of the present invention, a skin care product comprising the lipid particle is used for topical suppression of ROS in the skin of a patient.

Description

Technical Field

[0001] The present invention relates to Process for preparing lipid particles .

Background Art

[0002] Recently, skin care products such as creams, lotions or serums have become widespread, and these products consist of a fluid substance, usually a gel, in which lipid particles containing molecules of one or more cosmetic active ingredients are incorporated.

[0003] Examples of the aforementioned active ingredients are vitamins such as vitamins A, C, E and derivatives thereof, coenzyme Q10, minerals, antioxidants, natural extracts and peptides.

[0004] Among the factors known to cause damage to the skin are the so-called "free radicals". These cause lipid peroxidation. Among these, those containing electron-deficient molecular oxygen ("peroxyl"), particularly the so-called ROS (reactive oxygen species), cause damage when in excess, the most serious of which is premature skin aging.

[0005] In the lipid peroxidation process, lipids including unsaturated fatty acids and their esters are directly oxidized by molecular oxygen, and the electron-deprived lipid tends to recover its loss by extracting electrons from adjacent molecules, so that the damage can spread through a chain reaction to proteins and DNA in the cell nucleus.

[0006] Following these reactions, there is potential damage, namely lipid peroxidation, peroxidation of amino acids and proteins, enzymatic changes, and damage to protein structures.

[0007] ROS produced in mitochondria act in opposition and can directly damage mtDNA and other mitochondrial components. ROS can also damage the DNA of the cell nucleus.

[0008] For all these reasons, oxidative modifications of certain proteins can be significant aging factors. Therefore, products containing antioxidant active ingredients that can interact with and inhibit the activity of ROS are known and widely used. For example, these products are commercialized as follows:

[0009] Revitalift® Derm-Intensive 10% Pure Vitamin C (L'Oréal Paris).

[0010] Resveratrol B E Antioxidant Night Concentrate (SkinCeuticals).

[0011] Daywear Advanced Multi-Protection Antioxidant Cream SPF15 (Estée Lauder).

[0012] Anthelios AOX Daily Antioxidant Serum with Sunscreen (La Roche-Posay).

[0013] However, there are limitations to the products currently available for reducing ROS in the skin. For example, these products contain active ingredients that are sensitive to ROS, but the latter (the ingredient) has the drawback of either being in a free state or being incorporated into a stable matrix that has no affinity for ROS, i.e., lipid particles with an envelope for containment, which is designed to protect or carry the contents in a controlled and specific manner.

[0014] This matrix generally contains saturated polymers and / or lipids that are primarily stable against oxidation (Comunian et al. “Protection and controlled release of vitamin C by different micro / nanocarriers”, Crit Rev Food Sci Nutr. 2020, Dec 22; 1-22).

[0015] The matrices used in products known to date serve the purposes of protecting the absorbed active ingredients, making them more bioavailable to the body, i.e., enabling them to reach the circulatory system, and increasing skin penetration and sustained release.

[0016] However, for these reasons, the activity of the active ingredient is expressed equally across the entire area of ​​skin to which the product is applied, regardless of the localized concentration of ROS, and is not preferentially expressed in areas with higher concentrations of ROS where there is a greater need.

[0017] Furthermore, producing similar products requires the use of toxic organic solvents such as dichloromethane, chloroform, diethyl ether, and ether-methanol mixtures, or high temperatures between 60°C and 100°C (Ghasemiyeh et al., “Solid lipid nanoparticles and nanostructured lipid carriers as novel drug delivery systems: applications, advantages and disadvantages”, Res Pharm Sci. 2018 Aug; 13(4):288-303). As a result, the process is economically and energetically expensive. [Overview of the project]

[0018] In view of the limitations of the prior art described above, the main objective of the present invention is to provide a skincare product and a manufacturing process thereof that can improve upon the prior art in one or more of the above-mentioned aspects.

[0019] Within the scope of this objective, the object of the present invention is to provide lipid particles that are highly sensitive to ROS and capable of transporting incorporated active ingredients to regions containing ROS, particularly regions with high ROS concentrations.

[0020] Another object of the present invention is to provide a skin care product that has higher affinity for ROS than similar products known so far. Another object of the present invention is to provide a method for producing a skin care product that does not involve the use of organic solvents and high temperatures.

[0021] A particularly important object of the present invention is to provide a skin care product and a method for producing the same that are highly reliable, relatively easy to implement, and have competitive costs.

[0022] These and other objects that will become apparent later and the present problem are achieved by lipid particles. Here, each of the aforementioned particles comprises

[0023] (a) a matrix containing the following (i) to (iii), and

[0024] (i) a lipid component that accounts for 20% by weight or more and 60% by weight or less of the total weight of the lipid particles, and has a melting temperature of 40°C or higher and 55°C or lower

[0025] (ii) one or more unsaturated fatty acids that account for 20% by weight or more and 30% by weight or less of the total weight of the lipid particles

[0026] (iii) one or more excipients selected from surfactants, suspending agents, humectants and mixtures thereof, that account for 10% by weight or more and 12% by weight or less of the total weight of the lipid particles

[0027] (b) at least one antioxidant incorporated into the aforementioned matrix.

[0028] The objects and goals of the present invention are also achieved by the process for preparing the lipid particles according to the present invention, which includes the following steps. That is, the process comprises

[0029] (i) a step of melting the lipid component, and

[0030] (ii) a step of dispersing one or more unsaturated fatty acids in the molten lipid component of step (i);

[0031] (iii) a step of dispersing the following in water preheated to a temperature of 40°C or higher and 50°C or lower;

[0032] -at least one antioxidant; and

[0033] -one or more excipients;

[0034] (iv) a step of adding the dispersion obtained in step (ii) to the aqueous dispersion obtained in step (iii), and obtaining an emulsion while stirring;

[0035] (v) a step of cooling the emulsion obtained in step (iv) to a temperature of 5°C or higher and 15°C or lower to obtain an emulsion comprising lipid particles in the aqueous phase.

[0036] Furthermore, the objects and purposes of the present invention are also achieved by the lipid particles for use in topical treatment of conditions associated with the accumulation of ROS (reactive oxygen species) in the skin of a patient. Here, each of the aforementioned lipid particles comprises

[0037] (a) a matrix comprising the following (i) to (iii),

[0038] (i) a lipid component

[0039] (ii) one or more unsaturated fatty acids

[0040] (iii) one or more excipients selected from surfactants, suspending agents, humectants and mixtures thereof

[0041] and

[0042] (b) at least one antioxidant incorporated into the aforementioned matrix.

[0043] The objectives and goals of the present invention are also achieved by skincare products containing lipid particles according to the present invention.

[0044] Finally, the objectives and goals of the present invention are also achieved by the lipid particles according to the present invention, or by skincare products according to the present invention used for topical treatment of conditions associated with the accumulation of ROS in a patient's skin.

[0045] Further features and advantages of the present invention will become apparent from the following detailed description. Detailed Description of the Invention

[0046] In a first embodiment, the present invention relates to lipid particles, each of which comprises a matrix and at least one antioxidant incorporated into each particle.

[0047] The lipid particle matrix of the present invention contains a lipid component having a melting temperature of 40°C to 55°C in an amount of 20% to 60% by weight relative to the total weight of the lipid particles.

[0048] Advantageously, the aforementioned melting temperature is closer to skin temperature (37°C) than the melting temperatures of other waxes used to create lipid particles, such as microcrystalline wax, carnauba wax, and beeswax, which have melting temperatures of 65°C or higher.

[0049] In preferred embodiments, the lipid component is a mixture of mimosa wax (acacia declence), jojoba seed wax, sunflower seed wax, polyglycerin, pentaerythrityl distearate, and at least two transesterification products of polyglycerin with at least one wax selected from jojoba wax, mimosa wax, and sunflower seed wax.

[0050] Furthermore, the matrix of the lipid particles according to the present invention contains (ii) one or more unsaturated fatty acids, preferably polyunsaturated fatty acids, in an amount of 20% to 30% by weight relative to the total weight of the lipid particles, which have a high affinity for ROS, thereby giving the lipid particles of the present invention the property of interacting with ROS and releasing the active ingredient in a targeted manner. The lipid particles of the present invention thus have a matrix characterized by a high affinity for ROS.

[0051] In this specification, the term "affinity" means the principle of activity or the tendency of the lipid particles constituting it to inevitably interact with ROS.

[0052] As mentioned above, the affinity of ROS is measured by its iodine value.

[0053] As mentioned above, lipid particles commonly used today have a matrix that is stable against oxidation.

[0054] In this specification, the expression "stable matrix" means a matrix that is stable against oxidation, and in the case of a lipid matrix, this means an iodine value lower than 60g iodine / 100g, as measured according to the ASTMD1959-97 standard.

[0055] In a preferred embodiment, the lipid particle matrix according to the present invention has an iodine value of 60 g iodine / 100 g or more, as measured according to the ASTMD1959-97 standard.

[0056] The particle matrix of the present invention contains one or more unsaturated fatty acids, preferably selected from the group consisting of unsaturated fatty acids having C16 to C24 carbon atoms and mixtures thereof. In a preferred embodiment, the one or more unsaturated fatty acids are selected from the group consisting of linoleic acid, linolenic acid, α-linolenic acid, oleic acid and mixtures thereof.

[0057] Preferably, the matrix contains one or more unsaturated fatty acids, each comprising at least 60% by weight of polyunsaturated fatty acids relative to the total weight of unsaturated fatty acids.

[0058] The lipid particles of the present invention contain at least one antioxidant incorporated into the matrix.

[0059] Preferably, at least one antioxidant is selected from the group consisting of BHT (butylated hydroxytoluene), vitamin E, vitamin C, BHA (butylated hydroxyanisole), polyphenols, carotenoids, superoxide dismutase, and bisulfites.

[0060] In the context of this specification, the term "vitamin C" refers to ascorbic acid and its derivatives, such as sodium ascorbyl phosphate, ascorbyl tetraisopalmitate, 3-O-cetyl ascorbic acid, and ascorbyl glucoside.

[0061] A matrix of lipid particles rich in unsaturated and polyunsaturated fatty acids, which have a high affinity for ROS, is therefore capable of selectively transporting the antioxidants incorporated within it and functioning as a "scavenger" to neutralize ROS in ROS-rich skin areas.

[0062] Preferably, in the lipid particles of the present invention, at least one antioxidant is present in an amount of 5% to 20% by weight relative to the total weight of the lipid particles.

[0063] The lipid particle matrix according to the present invention further contains (iii) one or more excipients selected from surfactants, suspending agents, humectants and mixtures thereof, in an amount of 10% to 12% by weight relative to the total weight of the lipid particles.

[0064] Preferably, at least one excipient is selected from the group consisting of polysorbate, polyacrylate, xanthan gum, alkyl glucoside, and glycol.

[0065] Furthermore, the lipid particles of the present invention may further contain one or more active ingredients incorporated into the matrix. Here, one or more active ingredients are selected from the group consisting of vitamins, peptides, minerals, growth factors, and natural extracts.

[0066] The aforementioned active ingredients have the function of restoring physiological balance and the function of repairing and stimulating the self-repair mechanism of skin damaged by excessive concentrations of ROS.

[0067] In this specification, the term "active ingredient" refers to a substance that has biological activity or a substance that affects the appearance and condition of the skin.

[0068] In this specification, the term "biological activity" means that the substance has an effect on biological tissue, in this case the skin, or a cosmetic effect on the skin.

[0069] In a second embodiment, the present invention relates to a process for preparing lipid particles according to the present invention, comprising the following steps:

[0070] (i) A step of melting lipid components,

[0071] (ii) A step of dispersing one or more unsaturated fatty acids in the melted lipid components of step (i),

[0072] (iii) A step of dispersing the following in water that has been preheated to a temperature of 40°C or higher and 50°C or lower,

[0073] - at least one antioxidant; and

[0074] - One or more excipients;

[0075] (iv) Adding the dispersion obtained in step (ii) to the aqueous phase dispersion obtained in step (iii), and stirring to obtain an emulsion,

[0076] (v) The step of cooling the emulsion obtained in step (iv) to a temperature of 5°C to 15°C to obtain an emulsion containing lipid particles in the aqueous phase.

[0077] In step (iv), stirring is preferably carried out at a constant speed between 1,000 and 8,000 revolutions per minute.

[0078] Preferably, before step (v), the emulsion obtained in step (iv) is sieved through a net having pores in the range of 0.1 to 50 μm in size to obtain an emulsion containing lipid particles in the aqueous phase having a size in the range of 0.1 to 50 μm. The emulsion can be cooled in step (v) and then dried under vacuum at a temperature of 40°C or lower, and / or stabilized by adding preservatives such as sodium benzoate, potassium sorbate, isothiazolinone, phenoxyethanol, formaldehyde removers, and chelating agents.

[0079] In a preferred embodiment of the process according to the present invention, the lipid component is a mixture of at least two transesterifications of mimosa wax (acacia declence), jojoba seed wax, sunflower seed wax, polyglycerin, pentaerythrityl distearate, and polyglycerin-3 with at least one wax selected from jojoba wax, mimosa wax, and sunflower seed wax;

[0080] The selection of the wax mixture described above advantageously allows for the preparation of particles in a process that does not require high temperatures or organic solvents.

[0081] In a preferred embodiment, the process according to the present invention does not involve the use of an organic solvent.

[0082] The lipid particles of the present invention obtained as described above can then be incorporated into a skincare product selected from the group consisting of serums, creams, and lotions, and these (lipid particles) and the skincare product are mixed at a temperature of 40°C or lower and at a speed of 100 to 200 revolutions per minute until they are completely homogenized.

[0083] Accordingly, the present invention also relates to a skincare product containing lipid particles according to the present invention. The product, preferably selected from serums, creams, and lotions, is optionally packaged in an airtight container to prevent the generation of ROS inside the product.

[0084] The present invention also relates to the above-mentioned lipid particles and the above-mentioned skincare products for use in the topical treatment of conditions associated with the accumulation of ROS in the patient's skin.

[0085] Skin conditions associated with ROS accumulation include premature aging, loss of elasticity, loss of moisture, hyperpigmentation, skin discoloration, acne, and physiological imbalances.

[0086] The present invention also relates to lipid particles for use in the topical treatment of conditions associated with the accumulation of ROS in the skin of patients. Here, each lipid particle is

[0087] (a) A matrix containing the following (i) to (iii),

[0088] (i) Lipid components

[0089] (ii) One or more unsaturated fatty acids

[0090] (iii) One or more excipients selected from surfactants, suspending agents, humectants and mixtures thereof

[0091] and

[0092] (b) Contains at least one antioxidant incorporated into the matrix.

[0093] The present invention also relates to a method for treating a condition associated with the accumulation of ROS in a patient's skin by applying the aforementioned lipid particles or skincare products to the patient.

[0094] Next, the present invention will be described in relation to the following non-limiting embodiments.

[0095] Example 1: Preparation of lipid particles of the present invention

[0096] The procedure for preparing 1 kg of the composition containing the lipid particles of the present invention, which is used as an intermediate in the preparation of cosmetics, was as follows:

[0097] (i) 90 g of a blend of jojoba wax, mimosa wax, and sunflower seed wax (Acticia® MB (Acticia Gatefosse)) and 30 g of a blend of natural polyunsaturated fatty acids obtained from safflower oil (Vitamin F Forte (CLR Berlin)) were heated in a beaker at 55°C and stirred with a magnetic stirrer at 200 rpm for 10 minutes until the phase was completely melted.

[0098] (ii) 30 g of a mixture of natural polyunsaturated fatty acids obtained from safflower oil (Vitamin F Forte (CLR Berlin)) was added to the molten mixture obtained in step (i) while stirring at 200 rpm using a magnetic stirrer, maintaining the temperature at 55°C, until a homogeneous mixture of melted "fat" was obtained.

[0099] (iii) The aqueous dispersion was prepared by adding the following to 758 ml of water heated to 45°C, followed by stirring (at 500 rpm for 10 minutes).

[0100] - Decyl glucoside 20g,

[0101] - 100g sodium ascorbyl phosphate,

[0102] - Hyaluronic acid 2g;

[0103] (iv) The aqueous dispersion prepared in item (iii) was added to the fat mixture prepared in item (ii), and while maintaining the temperature at 48°C, the mixture was stirred at 3500 rpm for 10 minutes to obtain an emulsion of lipid particles in the aqueous phase.

[0104] (iv-a) The emulsion obtained in step (iv) was sieved through a net having pores with a diameter of 25 pm to obtain an emulsion in the aqueous phase of lipid particles with a diameter of 25 pm or less.

[0105] (v) The emulsion obtained in step (iv-a) was cooled to 10°C using a water bath to promote the solidification of the lipid portion.

[0106] It has been found that by manufacturing lipid particles and skincare products characterized by high affinity for ROS, and capable of transporting active ingredients incorporated into the lipid particle matrix to regions containing ROS, particularly regions with high ROS concentrations, the intended purposes and goals of the present invention can actually be achieved.

[0107] The skincare product incorporating lipid particles according to the present invention has the advantage of having a higher affinity for ROS than similar products currently on the market.

[0108] Furthermore, the present invention has perfected a manufacturing process for skincare products that does not involve the use of organic solvents or high temperatures.

[0109] The present invention, conceived in this manner, is subject to numerous modifications and variations within the scope of its technical concept. Furthermore, all details can be replaced with other technically equivalent elements.

[0110] In practice, the materials used are arbitrary, depending on the requirements and technical status, as well as incidental shapes and dimensions, as long as they are suitable for the specific use.

Claims

1. (i) A step of melting a lipid component having a melting temperature of 40°C or higher and 55°C or lower, which is a mixture of mimosa wax (acacia declence), jojoba seed wax, sunflower seed wax, pentaerythrityl distearate, and polyglycerin, and at least two transesterified products of jojoba wax, mimosa wax, and sunflower seed wax. (ii) A step of dispersing one or more unsaturated fatty acids selected from the group consisting of fatty acids having C16 to C24 carbon atoms and mixtures thereof in the melted lipid components of step (i), (iii) A step of dispersing at least one antioxidant selected from the group consisting of BHT (butylhydroxytoluene), vitamin E, vitamin C, BHA (butylhydroxyanisole), polyphenols, carotenoids, superoxide dismutase, and bisulfites, and one or more excipients selected from the group consisting of polysorbate, polyacrylate, xanthan gum, alkyl glucoside, and glycol in water that has been preheated to 40°C or 50°C or below, (iv) Adding the aqueous dispersion obtained in step (iii) to the dispersion obtained in step (ii), and stirring to obtain an emulsion, (v) A step of cooling the emulsion obtained in step (iv) to a temperature of 5°C to 15°C to obtain an emulsion containing lipid particles in the aqueous phase, A process for preparing lipid particles, characterized by including [a certain element].

2. The preparation process according to claim 1, characterized in that the preparation process does not involve the use of an organic solvent.

3. The preparation process according to claim 1, characterized in that the one or more unsaturated fatty acids are selected from the group consisting of linoleic acid, linolenic acid, alpha-linolenic acid, oleic acid, and mixtures thereof.