KR20240017376A - Skin care products and their manufacturing procedures - Google Patents

Abstract

The present invention is a lipid particle and a method for producing the lipid particle. The lipid particles include a matrix and at least one antioxidant contained in the matrix. In an embodiment of the invention, lipid particles are used for local inhibition of ROS (“reactive oxygen species”) in the skin of a patient. In an embodiment of the invention, skin care products comprising lipid particles are used for topical inhibition of ROS in the skin of a patient.

Description

Skin care products and their manufacturing procedures

The present invention relates particularly to lipid particles for use in skin care products.

Recently, skin care products comprising lipid particles containing one or more cosmetic active ingredient molecules, such as creams, lotions or serums consisting of fluid substances, usually gels, have become widespread.

Examples of such active ingredients are vitamins, such as vitamins A, C, E and their derivatives, coenzyme Q10, minerals, antioxidants, natural extracts and peptides.

Among the factors known to cause damage to the skin are so-called "free radicals." These cause lipid peroxidation. Among these, so-called ROS (reactive oxygen species), which contain oxygen molecules with electron deficiencies (“peroxyl”), cause damage in excess, the most serious of which is premature aging of the skin.

In the process of lipid peroxidation, lipids containing unsaturated fatty acids and their esters are directly oxidized by oxygen molecules, and the damage can propagate through a chain reaction, in which electron-deficient lipids also include proteins in the central nucleus and DNA. This is because it has a tendency to complete the loss by stealing electrons from adjacent molecules.

Therefore, some of the possible damages resulting from these reactions are lipid peroxidation, peroxidation of amino acids and proteins, enzyme alterations, and damage to protein structure.

ROS generated within mitochondria can adversely affect mtDNA and other mitochondrial components, directly damaging them. ROS can also damage nuclear DNA.

For all these reasons, oxidative modification of some proteins may be an important aging factor. Therefore, products containing antioxidant active ingredients that can interact with ROS and inhibit its activity are known and widely distributed. For example, these products are commercialized as follows:

- RevitaLift® Derm Intensive 10% Pure Vitamin C (L'Oreal Paris),

- Resveratrol B E antioxidant night concentrate (Skinceuticals)

- Daywear Advanced Multi-Protection Antioxidant Cream SPF 15 (Estee Lauder)

- Anthelios AOX Daily Antioxidant Serum with Sunscreen (La Roche-Posay)

However, currently available products for reducing ROS in the skin have limitations. For example, these products contain active ingredients that are sensitive to ROS, but are contained in a matrix in which the ROS are either free or stable, i.e., designed to protect the contents or transport them in a controlled, specific manner but have no affinity for the ROS. It has the drawback of being contained in lipid particles with a containment envelope.

These matrices typically consist primarily of saturated polymers and/or oxidation-stable lipids (Comunian et al. “Protection and controlled release of vitamin C by different micro/nanocarriers”, Crit Rev Food Sci Nutr. 2020, Dec 22 ;1-22]).

The matrices used in the products known to date have the purpose of protecting the active ingredients they contain, making them more bioavailable so they can reach the circulatory system and increasing skin penetration and gradual release.

However, for these reasons, the activity of the active ingredient is not preferentially applied to areas with higher ROS concentration, i.e., areas of greater need, but is expressed equally in all skin areas to which the product is applied, regardless of the local concentration of ROS. do.

Additionally, for the manufacture of similar products, it is necessary to use organic solvents such as dichloromethane, chloroform, diethyl ether and ether-methanol mixtures, which can be toxic, or high temperatures above 60°C and below 100°C (literature [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]). This results in an economically and energetically expensive process.

Taking into account the limitations of the prior art described above, the main goal of the present invention is to provide a skin care product and a method for producing the same that can improve the prior art in one or more of the aspects specified above.

Within this goal, the aim of the present invention is to provide lipid particles that have a high sensitivity to ROS and are capable of delivering the active ingredients contained therein to areas with ROS, especially to areas with higher ROS concentrations.

Another object of the present invention is to provide skin care products with greater affinity for ROS than similar products known to date. Another object of the present invention is to provide a method for producing skin care products that does not involve the use of organic solvents and the use of high temperatures.

The minimal object of the present invention is to provide a highly reliable, relatively easy to implement, and cost-competitive skin care product and method for manufacturing the same.

These tasks, as well as these and other objectives that will become apparent later, are achieved by lipid particles, each of which comprises:

(a) A matrix containing:

(i) 20% by weight or more and 60% by weight or less of a lipid component characterized by a melting temperature of 40°C or more and 55°C or less, based on the total weight of the lipid particles;

(ii) 20% by weight or more and 30% by weight or less of one or more unsaturated fatty acids based on the total weight of the lipid particles;

(iii) at least 10% by weight and up to 12% by weight of one or more excipients selected from surfactants, suspending agents, wetting agents and mixtures thereof, based on the total weight of the lipid particles; and

(b) at least one antioxidant included in the matrix.

The aims and objectives of the invention are also achieved by a method for producing lipid particles according to the invention, comprising the following steps:

(i) melting the lipid component;

(ii) dispersing one or more unsaturated fatty acids into the molten lipid component of step (i);

(iii) dispersing in water preheated to a temperature above 40°C and below 50°C:

- at least one antioxidant, and

- one or more excipients;

(iv) adding the dispersion obtained in step (ii) to the aqueous dispersion obtained in step (iii) under stirring to obtain an emulsion;

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

Moreover, the objects and objects of the present invention are also achieved by lipid particles for use in the topical treatment of conditions associated with the accumulation of ROS (“reactive oxygen species”) in the skin of a patient, wherein each lipid particle has: Includes:

(a) A matrix containing:

(i) lipid component;

(ii) one or more unsaturated fatty acids;

(iii) one or more excipients selected from surfactants, suspending agents, wetting agents and mixtures thereof;

and

(b) at least one antioxidant included in the matrix.

The aims and objectives of the invention are also achieved by a skin care product comprising lipid particles according to the invention.

Finally, the aims and objectives of the invention are also achieved by the lipid particles according to the invention or the skin care product according to the invention for use in the topical treatment of conditions associated with the accumulation of ROS in the skin of a patient.

Additional features and advantages of the present invention will become more apparent from the detailed description that follows.

In a first aspect, the invention relates to lipid particles, each of said particles comprising a matrix and at least one antioxidant contained therein.

The matrix of the lipid particles of the present invention includes (i) 20% by weight or more and 60% by weight or less of a lipid component having a melting temperature of 40°C or more and 55°C or less, based on the total weight of the lipid particles.

Advantageously, the melting temperature mentioned above is lower than the melting temperature of other waxes used to produce lipid particles, such as microcrystalline wax, carnauba wax, beeswax, which have a melting temperature above 65°C, at a temperature lower than the skin temperature (37°C). ) is closer to

In a preferred embodiment, the lipid component is mimosa wax ( Acacia decurrens ), jojoba seed wax, sunflower seed wax, polyglycerol, pentaerythrityl distearate, and polyglycerol and jojoba wax, mimosa wax, and sunflower seed wax. A mixture of at least two transesterification products of at least one wax selected from seed waxes.

In addition, the matrix of the lipid particle according to the present invention (ii) has a high affinity for ROS, thereby providing the lipid particle of the present invention with the property of interacting with ROS, thereby releasing the active ingredient in a targeted manner. It contains at least 20% by weight and up to 30% by weight of one or more unsaturated or preferably polyunsaturated fatty acids, based on the total weight of. Therefore, the lipid particles of the present invention have a matrix characterized by high affinity for ROS.

In this description, the term “affinity” refers to the tendency with which an active ingredient or a lipid particle containing it should interact with ROS.

As described above, ROS affinity is measured by the iodine index.

As described above, lipid particles commonly used today have an oxidation stable matrix.

In this description, the expression "stable matrix" means a matrix that is stable against oxidation, and in the case of a lipid matrix, it means an iodine index of less than 60 g iodine/100 g, where the iodine index is in accordance with the ASTM D1959-97 standard. It is measured according to

In a preferred embodiment, the matrix of lipid particles according to the invention has an iodine index of at least 60 g iodine/100 g, where the iodine index is determined according to the ASTM D1959-97 standard.

The matrix of the particles of the invention preferably comprises at least one unsaturated fatty acid selected from the group consisting of C16-C24 unsaturated fatty acids 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, alpha-linolenic acid, oleic acid and mixtures thereof.

Preferably, the one or more unsaturated fatty acids of the matrix comprise at least 60% by weight of polyunsaturated fatty acids based on the total weight of unsaturated fatty acids.

The lipid particles of the present invention include at least one antioxidant incorporated into the matrix.

Preferably, the at least one antioxidant is from the group consisting of BHT (butylhydroxytoluene), vitamin E, vitamin C, BHA (butylhydroxyanisole), polyphenols, carotenoids, superoxide dismutase and bissulfite. is selected from

In the context of this description, 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. do.

Therefore, a matrix of lipid particles rich in unsaturated and polyunsaturated fatty acids, which provide high affinity for ROS, allows selective delivery of the antioxidants they contain and acts as a “scavenger” in ROS-rich skin areas. Try to neutralize it.

Preferably, at least one antioxidant in the lipid particles of the present invention is present in an amount of 5% by weight or more and 20% by weight or less based on the total weight of the lipid particles.

The matrix of lipid particles according to the present invention further comprises (iii) at least 10% by weight and up to 12% by weight of one or more excipients selected from surfactants, suspending agents, wetting agents and mixtures thereof, based on the total weight of the lipid particles. do.

Preferably, the at least one excipient is selected from the group consisting of polysorbates, polyacrylates, xanthan gums, alkyl glucosides and glycols.

In addition, the lipid particles of the present invention further comprise one or more active ingredients contained in the matrix, wherein the one or more active ingredients are selected from the group consisting of vitamins, peptides, minerals, growth factors and natural extracts.

The above-mentioned active ingredients have the function of restoring physiological balance and restoring and stimulating the self-repair mechanism of skin damaged due to excessive ROS concentration.

The term “active ingredient” in this description refers to a substance that possesses biological activity or affects the appearance and condition of the skin.

The expression "biologically active" in this description means that the substance affects biological tissue, in this case the skin, or has a cosmetic effect on the skin.

In a second aspect, the invention relates to a method for producing lipid particles according to the invention, comprising the following steps:

(i) melting the lipid component;

(ii) dispersing one or more unsaturated fatty acids into the molten lipid component of step (i);

(iii) dispersing in water preheated to a temperature above 40°C and below 50°C:

- at least one antioxidant, and

- one or more excipients;

(iv) adding the dispersion obtained in step (ii) to the aqueous dispersion obtained in step (iii) under stirring to obtain an emulsion;

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

The stirring in step (iv) is preferably carried out at a constant speed of 1000 to 8000 revolutions per minute.

Preferably, before step (v), the emulsion obtained in step (iv) is sieved through a net with pores in the size range of 0.1 μm or more and 50 μm or less. An emulsion consisting of lipid particles in an aqueous phase is obtained. Then, after cooling in step (v), the emulsion can be dried under vacuum at a temperature below 40° C. and/or mixed with, for example, sodium benzoate, potassium sorbate, isothiazolinone, phenoxyethanol, It can be stabilized by adding preservatives such as formaldehyde remover and chelating agent.

In a preferred embodiment of the method according to the invention, the lipid component is selected from the group consisting of mimosa wax (acacia decurance), jojoba seed wax, sunflower seed wax, polyglycerol, pentaerythrityl distearate, polyglycerol 3 and jojoba wax, mimosa wax. and a transesterification product of at least one wax selected from sunflower seed wax.

The choice of wax mixtures described above advantageously allows the particles to be prepared in a manner that does not require high temperatures or organic solvents.

In a preferred embodiment, the process according to the invention does not involve the use of organic solvents.

The lipid particles of the invention obtained as described above can then be incorporated into skin care products selected from the group consisting of serums, creams and lotions, at a temperature below 40° C. and at a rate of 100 to 200 per minute until complete homogenization. It can be mixed with the skin care product at a rotating speed.

Therefore, the present invention also relates to skin care products comprising lipid particles according to the invention. The products, preferably selected from serums, creams and lotions and optionally packaged in airtight containers, are protected against the formation of ROS therein.

The invention also relates to the above-described lipid particles and the above-described skin care products for use in the topical treatment of conditions associated with the accumulation of ROS in the skin of a patient.

Skin conditions associated with the accumulation of ROS include premature aging, loss of elasticity, loss of hydration, hyperpigmentation, dyschromia, acne and physiological imbalance.

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 a patient, each lipid particle comprising:

(a) A matrix containing:

(i) lipid component;

(ii) one or more unsaturated fatty acids;

(iii) one or more excipients selected from surfactants, suspending agents, wetting agents and mixtures thereof;

and

(b) at least one antioxidant included in the matrix.

The present invention of course also relates to a method of treating conditions associated with the accumulation of ROS in the skin of a patient by applying to the patient the lipid particles or skin care products described above.

The invention will now be explained with reference to the following non-limiting examples.

Example 1: Preparation of lipid particles of the present invention

The procedure for preparing 1 kg of the composition comprising the lipid particles of the invention used as an intermediate in the manufacture of cosmetics was as follows:

(i) 90 g of a blend of jojoba wax, mimosa wax and sunflower seed wax (ACTICIRE® MB, ACTICIRE-GATTE FOSSE) and 30 g of a natural polyunsaturated fatty acid blend obtained from safflower oil (Vitamin F forte, CLR Berlin), Melting in the beaker by heating at a temperature of 55° C. with magnetic stirring at 200 rpm for 10 minutes until the phase is completely melted;

(ii) 30 g of a natural polyunsaturated fatty acid mixture obtained from safflower oil (Vitamin F forte, CLR Berlin) was magnetically stirred at 200 rpm while maintaining the temperature at 55° C. until a homogeneous “fat” melt mixture was obtained. adding to the molten lipid mixture obtained in step (i) under;

(iii) preparing an aqueous dispersion by subsequently adding under stirring (500 rpm for 10 minutes) to 758 ml of water heated to 45°C:

- 20 g of decylglucoside,

- 100 g of sodium ascorbyl phosphate,

- 2 g of hyaluronic acid;

(iv) adding the aqueous dispersion prepared in step (iii) to the fat mixture prepared in step (ii) while maintaining the temperature at 48° C. with stirring at 3500 rpm for 10 minutes to obtain an emulsion of lipid particles in the aqueous phase. step;

(iv-a) sieving the emulsion obtained in step (iv) through a net with pores of 25 μm in diameter to obtain an emulsion of lipid particles with a diameter of 25 μm or less in an aqueous phase;

(v) cooling the emulsion obtained in step (iv-a) to 10° C. by means of a water bath to accelerate coagulation of the lipid portion.

In fact, the present invention provides lipid particles and skin care that are characterized by a high affinity for ROS and are capable of delivering the active ingredients contained therein to the matrix of lipid particles at sites with ROS, especially at sites with higher ROS concentrations. It has been found that manufacturing the product achieves its intended goals and objectives.

Skin care products comprising lipid particles according to the invention advantageously have a greater affinity for ROS than similar products available on the market today.

Additionally, the present invention has perfected a method of manufacturing skin care products that does not involve the use of organic solvents and the use of high temperatures.

The present invention thus conceived is susceptible to various modifications and changes, all of which are within the scope of the concept of the present invention; Moreover, every detail can be replaced by another technically equivalent element.

In practice, the materials used can be arbitrary depending on the requirements and state-of-the-art technology, provided they are compatible with the specific application as well as conditional shapes and dimensions.

Claims (14)

As lipid particles,
Each particle,
(a) matrix and
(b) at least one antioxidant included in the matrix
Including,
The (a) matrix is,
(i) 20% by weight or more and 60% by weight or less of a lipid component having a melting temperature of 40°C or more and 55°C or less, based on the total weight of the lipid particles;
(ii) at least 20% by weight and not more than 30% by weight of one or more unsaturated fatty acids, based on the total weight of the lipid particles;
(iii) a lipid particle comprising at least 10% by weight and up to 12% by weight of one or more excipients selected from surfactants, suspending agents, wetting agents and mixtures thereof, based on the total weight of the lipid particle. According to paragraph 1,
The lipid component is selected from mimosa wax ( Acacia decurrens ), jojoba seed wax, sunflower seed wax, polyglycerol, pentaerythrityl distearate, and polyglycerol and jojoba wax, mimosa wax, and sunflower seed wax. Lipid particles that are a mixture of at least two of the transesterification products of at least one wax. According to claim 1 or 2,
The matrix has an iodine index of at least 60 g iodine/100 g, wherein the iodine index is measured according to the ASTM D1959-97 standard. According to any one of claims 1 to 3,
The lipid particle, wherein the one or more unsaturated fatty acids comprise at least 60% by weight of polyunsaturated fatty acids based on the total weight of the unsaturated fatty acids. According to any one of claims 1 to 4,
The lipid particle, wherein the at least one antioxidant is present in an amount of 5% by weight or more and 20% by weight or less based on the total weight of the lipid particle. According to any one of claims 1 to 5,
Lipid particles, wherein the one or more unsaturated fatty acids are selected from the group consisting of C16-C24 fatty acids and mixtures thereof. According to any one of claims 1 to 6,
Wherein the at least one excipient is selected from the group consisting of polysorbates, polyacrylates, xanthan gum, alkyl glucosides, and glycols. According to any one of claims 1 to 7,
The at least one antioxidant is selected from the group consisting of BHT (butylhydroxytoluene), vitamin E, vitamin C, BHA (butylhydroxyanisole), polyphenols, carotenoids, superoxide dismutase, and bissulfite. , lipid particles. According to any one of claims 1 to 8,
A lipid particle further comprising one or more active ingredients included in the matrix, wherein the one or more active ingredients are selected from the group consisting of vitamins, peptides, minerals, growth factors and natural extracts. A method for producing lipid particles according to the present invention, comprising:
(i) melting the lipid component;
(ii) dispersing one or more unsaturated fatty acids into the fused lipid component of step (i);
(iii) in water preheated to a temperature above 40°C but below 50°C,
- at least one antioxidant, and
- One or more excipients
dispersing;
(iv) adding the dispersion obtained in step (ii) to the aqueous dispersion obtained in step (iii) under stirring to obtain an emulsion;
(v) cooling the emulsion obtained in step (iv) to a temperature of not less than 5° C. and not more than 15° C. to obtain an emulsion consisting of lipid particles in an aqueous phase. According to clause 10,
A method of preparation, wherein the method does not involve the use of an organic solvent. Lipid particles for use in the topical treatment of conditions associated with the accumulation of ROS (“reactive oxygen species”) in the skin of a patient, comprising:
Each lipid particle:
(a) Matrix; and
(b) at least one antioxidant included in the matrix
Includes, and the matrix is,
(i) lipid component;
(ii) one or more unsaturated fatty acids;
(iii) lipid particles comprising one or more excipients selected from surfactants, suspending agents, wetting agents and mixtures thereof. A skin care product comprising lipid particles according to any one of claims 1 to 9. Lipid particles according to any one of claims 1 to 9 or a skin care product according to claim 13 for use in topical treatment of conditions associated with the accumulation of ROS in the skin of a patient.