WO2000002530A1 - Saline and mineralized aqueous solution, and its use in cosmetics and dermopharmaceutics - Google Patents

Abstract

The invention concerns a cutaneous interactive aqueous base, biomimetic with the biodermal cell water, comprising an aqueous phase and a dissolved phase inorganic for the major part and comprising several mineral salts, whereof the weight concentration is less than 2 wt. % of said aqueous base, and whereof the composition is predetermined for adjusting at least the three following bioelectric parameters of the base in the following ranges of values respectively: pH not less than 5, and not more than 8; redox potential ranging between 10 and 29; resistivity not less than 80, and not more than 8000 ohms/cm/cm<2>.

Description

Saline and mineralized aqueous solution, and its use in cosmetics and dermo-pharmacy

The present invention relates to a synthetic aqueous base, and to its cosmetic or dermopharmaceutical use.

Today, in cosmetics or dermo-pharmacy, water, the main constituent of the living world, and in particular of the human body, is considered only as a simple excipient, making it possible to complete 100% (qs 100) the formula of any product. cosmetic or dermopharmaceutical. Consequently, only the bacteriological quality of the water used for this purpose, for example mineralized water, imports and is controlled. The present invention begins with the observation that water, the main component of cosmetic and dermo-pharmaceutical products, does not entirely correspond, as regards its composition and / or properties, to biodermal cellular water, and in particular epidermal cell water. Consequently, this water is not biocompatible with skin cells, in particular keratinocytes, so that it can in certain cases alter the various equilibria or cutaneous cell cycles, in particular participating in certain oxidation processes.

The thermal waters used in certain cosmetic or dermo-pharmaceutical preparations certainly have certain biological properties, due in particular to their content of metal ions or trace elements. However, they are also unsuitable, in particular because of their too high redox potential.

The present invention therefore relates to an aqueous, saline and mineralized base, improving the biomimicry of water with epidermal or biodermal cellular water, in particular epidermal or cutaneous cellular water, otherwise bringing an almost total biomimicry with the latter.

The invention relates to and provides an interactive cutaneous, biomimetic aqueous base with biodermal cellular water, comprising on the one hand an aqueous phase, and on the other hand a mainly inorganic dissolved phase and comprising several mineral salts, the weight concentration of which is less than 2% by weight of said aqueous base, and the composition of which is predetermined to adjust at least the following three bioelectric parameters of said base, respectively in the following ranges of values:

- pH greater than or equal to 5, and less than or equal to 8 - redox potential between 10 and 29 resistivity greater than or equal to 80, and less than or equal to 8000 ohms / cm / cm ² .

According to the present invention, it is therefore the choice of the bioelectric or bioelectronic properties of the aqueous solution, and their adjustment, which provides the biomimicry of this water with biodermal cellular water, and in particular skin cell water.

An aqueous base according to the invention therefore has good affinity with the skin. It is perfectly biocompatible with the latter, and respects both the interior environment and the exterior environment of skin cells, in particular.

An aqueous base in accordance with the invention has moreover been found to exert a bioregulatory activity with respect to skin cells. In particular, an aqueous base according to the invention allows cell viability, for example of keratinocytes, at least equal to three hours. Any aqueous base according to the invention behaves like the water used in the composition of the skin, in particular of the epidermis.

By "biomimetic" is meant the fact that any aqueous base according to the invention temporarily exerts the biomechanical, biophysical, physiological (in particular cell viability) or biological function or activity of biodermal cell water. In particular, the skin as a living biological medium cannot temporarily distinguish between its own cellular water and any aqueous base according to the invention.

By various in vivo tests, it has been observed that an aqueous base according to the invention, brought into contact with the skin, contributes to the hydration of the latter, while improving its appearance (suppleness, radiance, and reduction of wrinkles ). Such a solution also prevents oxidation and aging of the skin.

Advantageously, the composition of the dissolved phase is determined to adjust the osmotic pressure of the aqueous base to a value between 70 and 1500 mosmole, and preferably between 200 and 400 mosmole, for example between 280 and 320 mosmole.

As regards the dissolved phase, for example, the inorganic salts are each chosen from the group consisting of calcium chloride, potassium chloride, potassium hydrophosphate, magnesium chloride, magnesium sulfate , sodium chloride, sodium hydrocarbonate, sodium hydrophosphate. Preferably, the aqueous base comprises at least two inorganic salts respectively having the following compositions, expressed in g per liter of aqueous phase, namely:

0.05 <[CaXn, 2H ₂ 0] <1, X being an anion compatible with calcium, and n an integer corresponding to the neutrality of the salt 0.10 <[KC1] <1

0.01 <[KH ₂ P0 ₄ ] <0.2

0.01 <[MgCl ₂ , 6H ₂ 0] <1

0.01 <[MgS0 ₄ , 7H ₂ 0] <0.5 0.5 <[NaCl] <40

0.03 <[NaHC0 ₃ ] <3

0.04 <[Na ₂ HP0 ₄ ] <5

Preferably CaXn is equal to CaCl ₂ .

Advantageously, the dissolved phase comprises the eight inorganic salts previously defined, with the concentrations or compositions respectively and previously identified.

Preferably, the dissolved phase comprises trace elements, in particular chosen from the group comprising zinc, copper, silica, sulfur, selenium, iron, iodine, cobalt, nickel, chromium, tin, fluorine and vanadium, as well as magnesium, manganese and silicon.

The aqueous base comprises for example buffer adjuvants making it possible to regulate or adjust its pH.

The invention also relates to an interactive skin base as defined above, in particular biphasic, for example a water in oil emulsion, or oil in water. The term “aqueous base” means any constituent or component, whether main or not, as regards its weight composition, which is used in the composition of a cosmetic or personal hygiene product, or else for dermo-pharmaceutical use. By "cutaneous interactive aqueous base" is meant any aqueous medium having the property that said medium maintains, without inhibiting or exacerbating them, all of the functional equilibria of the skin, and this in addition to the topical bioactivity of this base, resulting biological activity vis-à-vis the skin of one or several constituents in the dissolved phase, synergistically or not.

An interactive cutaneous aqueous base, as defined above, therefore generally has a primary function and a secondary function. The primary function is both to protect and maintain, even to restore the main biological and physiological skin balances, and to create an appropriate stable dosage form (milk, cream, etc.). The secondary function consists of possibly treating the skin by providing it with one or more benefits topically, in particular therapeutically.

By "topical bioactivity" is meant the fact that globally the cutaneous interactive base exhibits or manifests, topically, a cosmetic or therapeutic benefit, at the level of the skin, for example of the epidermis.

The present invention also relates to a cosmetic or personal hygiene product, or for dermo-pharmaceutical use, comprising at least 98% by weight, if not entirely, of an interactive skin base, as defined above.

The invention also relates to the use of an aqueous solution (aqueous phase plus dissolved phase) as defined above, in particular formulated, for obtaining an interactive cutaneous, biomimetic aqueous base with biodermal cellular water, having a stable topical dosage form, in particular monophasic, diphasic, or triphasic, and for cosmetic or personal hygiene use, or for dermo-pharmaceutical use.

By "dosage form" is meant any topical form or presentation allowing the interactive skin aqueous base to play a functional activity with respect to the skin. The present invention also presents the following embodiments: - The dissolved phase is essentially inorganic, in that it comprises a concentration by weight of organic constituents, or equivalent, for example biological, less than 0.1% by weight of the aqueous base

- the pH of the aqueous base is between 5 and 7

- the redox potential of the aqueous base is between 20 and 29 - the resistivity of the aqueous base is between 120 and 200 ohms / cm / cm ² .

The present invention is now described with reference to examples.

Example No. 1

The table below defines, by way of example, an aqueous base in accordance with the invention, balanced and mineralized, colorless and odorless.

TABLE 1

Trace elements can be added in the form of salts: sulfates, gluconates, or any other form compatible with topical use, such as chelates.

Example 2 Table No. 2 below defines four compositions of an aqueous, saline and mineralized base, in accordance with the invention, with the values obtained for their bioelectric parameters.

TABLE 2

Exemple N°3

Example 3

This example defines the composition of a cosmetic product, obtained with an aqueous base according to the present invention, more precisely base A of Example 2:

Water base A qs 100

Triglycerides of caprylic, capric and linoleic acids 5-10

Caprylic and capric acid triglycerides 5-10

Behenyle peanut alcohol and peanut glucoside 1-5

Triglycerides of caprylic, capric and succinic acids 5-10 Soda 0.1-2

Glycerin 2-3

Sucrose Distearate 1-3

Sucrose stearate 1-3

Phenoxyethanol 0.1-0.5 Sclerotium gum 0.1-0.5

Propyl parahydroxybenzoate 0.1-0.5

Butyl parahydroxybenzoate 0.1-0.5

Ethyl parahydroxybenzoate 0.1-0.5

Methyl parahydroxybenzoate 0.1-0.5

Example No. 4: Study of the cell viability over 8 hours of normal human keratinocytes, in the presence of an aqueous base according to the invention; comparison with other aqueous media. The objective of this study is to evaluate the cytotoxicity of an aqueous base according to the invention, and more precisely of the aqueous base according to composition A of Table 2 of Example 2, in comparison with the cytotoxicity of other aqueous media , and this on culture of normal human keratinocytes, for a contact time of eight hours. The keratinocytes are thus brought into contact with the following aqueous media: distilled water tap water - physiological saline aqueous base according to composition A The cytotoxicity of the aqueous media studied is assessed by measuring the activity of the itochondrial system succinate-tetrazolium reductase of cells that remain alive. WST-1, i.e. (4- (3- (4- Iodophenyl) -2 (4-nitrophenyl) -2- (4-nitrophenyl) -2H-5- tetrazolio) -1, 3-benzenedisulfonate), is reduced into a colored precipitate of formazan. Cell viability is determined by spectrophotometric reading at 450 nm. The following operating procedure is implemented:

* seeding:

The keratinocytes (KPTJ were seeded in 96-well microplates (Falcon ^® brand) at 20 000 cells per well in 200 .mu.l of medium KSFM

(GIBCO). The plates are incubated for 48 hours at 37 ° C. in a humid atmosphere containing 5% carbon dioxide.

* treatment: After rinsing with PBS buffer, the various aqueous media are deposited in contact with the cells to replace the KSFM medium, at the rate of 200 μl per well. Each determination is made in three stages. Six wells receive standard KSFM medium, and serve as controls. Six wells are the blanks for the reaction and do not contain cells. The plates are incubated for 8 hours at 37 ° C. The WST-1 test is carried out after 30 minutes of contact, 1 hour, 3 hours, 5 hours and 8 hours. * Coloring:

After elimination of the medium, the cells are washed four times with 100 μl of PBS. 100 μl of KSFM medium containing ST-1 (final dilution 1:10) are added to each well. The 6 wells containing no cells receive medium (with ST-1) and serve as blank for spectrometric analysis. The contact time of the reagent is 30 n at 37 ° C.

* Analysis:

The optical density is read with the ELISA microplate reader at 450 nm.

CONCLUSIONS An aqueous base according to the present invention premet in vitro, over eight hours, cell survival superior to that of the other aqueous media treated.

With a physiological saline, the cells of rounded shape, die after a few hours. With distilled (hypotonic) water and tap water, cells die very quickly.

Cell survival with an aqueous base according to the invention is in any case greater than that obtained with physiological saline (NaCl 9 g / 1). A modification of the cell morphology is however to be noted, with an aqueous base according to the invention, but most of the cells are still alive after eight hours.

Claims

1 / Interactive cutaneous aqueous base, biomimetic with biodermal cellular water, comprising on the one hand an aqueous phase, and on the other hand a mainly inorganic dissolved phase and comprising several mineral salts, whose weight concentration is less than 2% by weight of said aqueous base, and the composition of which is predetermined to adjust at least the following three bioelectric parameters of said base, respectively in the following ranges of values: pH greater than or equal to 5, and less than or equal to 8 redox potential between 10 and 29 - resistivity greater than or equal to 80, and less than or equal to 8000 ohms / cm / cm ² . 2 / A base according to claim 1, characterized in that the dissolved phase is essentially inorganic, in that it comprises a concentration by weight of organic constituents, or equivalent, less than 0.1% by weight of said aqueous base. 3 / aqueous base according to claim 1, characterized in that the composition of the dissolved phase is predetermined to adjust the osmotic pressure of said base to a value between 70 and 1500 mosmole, and preferably between 200 and 400 mosmole, for example included between 280 and 320 mosmole. 4 / aqueous base according to claim 1, characterized in that the inorganic salts are chosen from the group consisting of calcium chloride, potassium chloride, potassium hydrophosphate, magnesium chloride, magnesium sulfate, sodium chloride, sodium hydrocarbonate, sodium hydrophosphate. 5 / aqueous base according to claim 4, characterized in that it comprises at least two salts inorganic, having respectively the following compositions, expressed in g per liter of aqueous phase, namely: 0.05 <[CaXn, 2H ₂ 0] <1, X being an anion compatible with calcium, and n an integer corresponding to the neutrality of the salt 0, 10 <[KC1] <1 0.01 <[KH ₂ P0 ₄ ] <0.2 0.01 <[MgCl ₂ , 6H ₂ 0] <1 0.01 <[MgS0 ₄ , 7H ₂ 0] <0.5 0.5 <[NaCl] <40 0.03 <[NaHC0 ₃ ] <3 0.04 <[Na ₂ HP0 ₄ ] <5 6 / aqueous base according to claim 5, characterized in that the dissolved phase comprises eight inorganic salts, the respective compositions of which have the values defined in claim 5. 7 / aqueous base according to claim 1, characterized in that the dissolved phase comprises trace elements, in particular chosen from the group comprising zinc, copper, silica, sulfur, selenium, iron, iodine, cobalt, nickel, chromium, tin, fluorine and vanadium, as well as magnesium, manganese and silicon. 8 / aqueous base according to claim 1, characterized in that the pH is between 5 and 7. 9 / aqueous base according to claim 1, characterized in that the redox potential is between 20 and 29. 10 / aqueous base according to claim 1, characterized in that the resistivity is between 120 and 200 ohms / cm / cm ² . 11 / aqueous base according to claim 1, characterized in that it is in biphasic form, for example of a water in oil emulsion, or oil in 1 ea. 12 / Cosmetic or personal hygiene product, or for dermo-pharmaceutical use, characterized in that it comprises at least 95% by weight of a base according to any one of claims 1 to 11. 13 / Product according to claim 12, characterized in that the aqueous base represents the whole of the weight composition of said product. 14 / Use of an aqueous solution comprising on the one hand an aqueous phase, and on the other hand a mainly inorganic dissolved phase and comprising several mineral salts, the weight concentration of which is less than 7% by weight of said aqueous base, and whose composition is predetermined to adjust at least the following three bioelectric parameters of said base, respectively in the following ranges of values: - pH greater than or equal to 5, and less than or equal to 8 - redox potential between 10 and 29 resistivity greater than or equal to 80, and less than or equal to 8000 ohms / cm / cm ² , for obtaining a base cutaneous interactive water, biomimetic with biodermal cellular water.