MXPA99006701A - Cosmetic or dermo-phamaceutical products compatible with cutaneous ecology - Google Patents

Abstract

These products are characterised in that they contain for at least 90%by weight, only of constituents biologically compatible with the skin and the skin cells, expressing together interactively at least a topical bioactivity, identical to or different from the bioactivity of at least one constituent biologically compatible with the skin, and providing to said product acomposition in stable topical galenic form, practically excluding any excipient biologically non-compatible with the skin other than water.

Description

COSMETIC OR DERMOFARMACEUTICAL PRODUCTS CONCERNING general way all the products destined to the skin, or to superficial parts of the human body, which are close to the skin, such as nails and hair.

Traditionally, a cosmetic or dermatological product comprises one or several active ingredients, and an excipient or vehicle in which the active ingredient (s) is distributed or dispersed, the total that is formulated for a topical application, for example in the form of gel or cream.

By "active principle" is meant any compound, any composition, or any product that exerts a biomechanical, biophysical, physiological, or biological activity, in relation to the skin, and in particular of the epidermis, and that has all nature and physical-chemical forms, required for the treatment or the action selected or retained in relation to .__. the skin . _ # REF. 30792 The chemical active ingredient (s) contained, are mostly foreign to the skin; see EP-0 475. 851. In certain cases, these active principles are natural products, that is, obtained from products or substances of nature, for example in the vegetable kingdom; see EP-0 477 833. In other cases, these active principles are products or constituents found in the skin; see WO-94/18945 and EP-0 627 223.

"On the other hand, cosmetic or dermo-pharmaceutical products are known, which do not comprise an excipient or vehicle proper, but in the form of a complex, associating various products, see EP-0 379 846. In certain examples, one or some compounds , but not all of these last, are natural compounds; see O-89/05629.

Currently, to the owner's knowledge, nobody has Interested, for cosmetic or therapeutic purposes, in the skin, and in particular in the epidermis, considered as a medium or ecological system, of which it is necessary to respect the balance, except certain works that concern only the ecology of the cutaneous bacterial flora.

Such is the object of the present invention. 25 *** _ In all its generality, the invention proposes a new generation of cosmetic products, or of corporal hygiene, or dermo-therapeutic, comprising at least 98% by weight of the biodermic constituents, each selected by its nature biocompatible and cytocompatible with the skin cells, and preferably biomimetic with a compound of the skin, particularly of the epidermis. These biodermic constituents are selected and formulated, on the one hand $ _ to jointly express at least one bio-activity topically, identical or different from the bioactivity, of at least one biodermic constituent, and on the other hand to confer to the product a composition in a stable topical galenical form, as far as the administration mode * _ is concerned, for example gel , milk, cream, lotion, make-up remover, for a cosmetic or body hygiene product.

From the previous definition it results, by difference with traditional cosmetic or dermatological products, that * 20 it is no longer possible in particular to distinguish between active principle (s) and excipient or vehicle. Practically, a product according to the present invention behaves as well as one or more active ingredients, than as an excipient. And every r * biodermal constituent should be seen, as well as a • 5- cutaneous constituent, and / or an active principle, and / or a galenic agent, for example a thickener or surfactant.

The composition of a product according to the present invention excludes virtually all non-biodermic excipients in addition to water or an aqueous phase.

It follows from the above definition that a product according to the present invention can not be assimilated: 10 - By one or several biodermic active principles, comprising biomimetics, formulated in a stable galenic form, with a traditional excipient or vehicle fifteen - . 15 - by a complex of natural products, in general without excipient or vehicle itself, since it comprises practically in its entirety particular natural products, namely biodermic constituents.

According to the foregoing definition, any product limited to one or more active biodermic products, distributed in one way or another in water or in an aqueous phase, majority by weight in the total composition of the product, is also excluded; by * J ' A product according to the invention is biphasic or monophasic, or consists of several emulsifying phases or not, 1 to obtain any appropriate topical form, for example cream, emulsion, lotion, serum, milk, gel, fluid, ... etc.

By "excipient" or "carrier" is meant in the traditional manner any compound or composition, such as dispersing diluent, or solvent, adapted to form the required topical form, for example a cream, a gel, an oil, a lotion, ... etc. This composition is completed by various adjuvants well known to those skilled in the art, such as moisturizing agents, astringents, humidifiers, emollients, etc.

By "interactive" is meant the property according to which the composition of a product according to the invention maintains, without inhibiting or exacerbating it, all the functional biological balances of the skin, and this in addition to the > topical bioactivity of the aforementioned composition, which results from the biological activity in relation to the skin of one or more biodermic constituents, synergistically or not. ~ f A product according to the invention then has three functions. A first function is both to protect .1 and maintain, until restoring the main cutaneous, biological and physiological balances. A second function is to create an appropriate stable galenic form (milk, cream, ... etc.). A third function is to treat the skin, providing one or several benefits topically, particularly therapeutic or cosmetic.

By "galenical form", any form or presentation is understood, adapted to the way of administration that is has, that allows the product to perform a functional activity in relation to the skin.

By "biodermic constituent", it is understood. any compound or product that it carries in the composition of the skin, particularly of the epidermis, it being understood that this constituent is considered in an isolated state, under a form identical to its natural form, or modified in relation to its natural form, but remaining cytocompatible with the skin, whatever its mode of production or production , in particular by separation from living cutaneous products, by biosynthesis, by a biotechnological process, or even by genetic recombination.

By "bioactive" is meant the fact that the component or constituent considered presents itself »" 4 a biological activity within the epidermis, or even participate in any biological process, such as metabolism, in the epidermis.

By "topical activity" is meant the fact that, overall, the cutaneous interactive base exhibits or manifests, 4 by topical route, a cosmetic or therapeutic benefit, * - _ level of the skin, for example of the epidermis.

"Cytocompatibility with the skin" is understood as the property according to which the retained biodermal constituent has a cytotoxicity of less than 10% in relation to that of a human keratinocyte cell culture, that is to say it remains almost neuttro in relation to cellular feasibility and the morpho-differentiation of keratinocytes.

This cytocompatibility can be evaluated by the following routine examination.

Normal human keratinocytes from plastic surgery are grown in condition under submerged condition in defined medium (MCDB 153) supplemented with 10 ng / ml of an epidermal growth factor, 5 μg / ml of insulin, 0.1 mM of ethanolamine, 0.1 mM of phosphoethanolamine, and 2% acids non-essential amino acids, this medium allows the culture of keratinocytes without presence, neither of serum nor of living nutritive cells (sT3 fibroblasts); its slight calcium content (0.1 mM) favors cell growth.

The biodermic constituents are evaluated in terms of their ability to induce cytopathic effects on sub-confluent cultures. The contact times are 6 hours, 12 hours, 24 hours and 36 hours.

The cellular feasibility is measured quantitatively by indirect counting of the living cells after their labeling with a vital dye. The neutral red system (3-amino-7- dimethyl-amino-2-methylphenasine hydrochloride) measures the dye passage activity through the plasmid membrane and storage in the lysosomes of the available cells.

The total incorporation of neutral red is proportional to the number of living cells in culture.

The incorporated colorant is extracted by an acetic acid / ethanol solvent and quantified by spectrophotometric measurement. The results are compared in relation to the standard crops, qualitatively, and expressed in optical density (OD) and / or percentage of optical density in relation to the negative control (untreated culture).

In the variation near the strains used, a percentage greater than or equal to 90% of optical density for a crop put in contact with the biodermic constituent examined, in relation to the negative control, expresses that said constituent is cytocompatible with the skin.

By "biomimetics" is meant the fact that the biodermal constituent retained in the structure of and / or exerts the function or biomechanical, biophysical, physiological, or biological activity of all skin compounds, ie of all skin compounds that can be isolated or separated by fractionation of the dermis and or of the epidermis, or even of any compound whose existence can be characterized or evidenced in the dermis and / or in the epidermis, or even of any compound that can be assimilated by the skin and otherwise serve nutrient cells constitutive of the latter.

In other words, the skin, as a living biological medium, can not distinguish between its own biodermic constituents.

Preferably, the biodermic constituents are selected from the species or entities, biological, mineral, organic, or biochemical, constitutive of the skin, whatever the effective origin of the constituents produced on or in the skin.

The biodermic constituents can be selected from the constituent molecules of the epidermis and the dermis. By way of example, it will be retained: 10 - different lipids, fluids or concretes, such as oleic acid, essential fatty acids, mono, di- and triglycerides, linoleic acid, squalene, stearic acid, glycerol monostearate . 15 - specific lipids, such as stearic acid, cholesterol, ceramides, cholesterol-ester or sulfate, .. "saturated diglycerides, - r - Í. 20 - nucleic acids, - mucopolysaccharides, such as hyaluronic acid the collagens The biodermic constituent can also be selected from skin nutrients, ie the compounds or compositions that can be metabolized by the skin cells.

By way of example, all the elements, or fragments of elements, useful for the metabolism of the skin, such as cutaneous acids, fatty acids, vitamins, peptone, casein, caseinates, glycoproteins, will be cited. "to 10 immunoglobulins, complex lipids, amino acids, oligoelements, whey.

If necessary, the composition of a cosmetic product, or body hygiene, or dermo-pharmaceutic, according to the The present invention can be completed at a height of a maximum of 2%, by non-biodermic constituents, but cytocompatible with the latter, necessary for the galenic formation of said product, and / or to complete the - Topical bioactivity of the product. By way of example, will mainly mention perfumes, and very incidentally and exceptionally, certain minority adjuvants necessary for the good preservation of the stability and purity of the cosmetic or dermatological product. .- _ '•' -ti The biodermic constituents that make up almost all, if not all, of a product according to the invention, are formulated and obtained according to traditional techniques, for example in biphasic form, which are constituted by a water-in-oil or oil-in-water dispersion. .

Tables 1 to 3 combine examples of biodermic constituents to formulate an oil phase, and / or an aqueous phase, and complete the formulations according to the applications of the cosmetic product. In these tables, the left column expresses a recommendation, it being understood that, as said above, each of the biodermic constituents is by nature cytocompatible with the skin, and biomimetic with the latter. The other columns express the class to which the aforementioned components belong, according to the following classification: Class 1: 20 Substantially cytocompatible and / or bioassimilable compounds, present in the constitutive state in the skin % V (water, amino acids, oligoelements, vitamins ...).

Class 2: - Macromolecules obtained biotechnologically, from synthesis or extraction, of composition and structure identical or almost identical to the constituents of the skin (sodium salt of DNA, sodium hyaluronate ...).

These compounds are cytocompatible with the skin, but may present metabolic interactions within the framework of biological or physiological processes. Its biological action is however comparable to that of the compounds present in the natural state in the skin (biomimicry).

The compounds of classes 1 and 2 are interactive, that is, they play both active and excipient roles.

Class 3: Compounds useful and assimilated by the skin, if possible of food or dietary origin, or authorized in food, but must be cytocompatible.

These compounds are interactive: They play both a "dermo-dietetic" and excipient role.

Class 4 Inert compounds, that is to say that they do not cause any chemical, biological or inological incidence with the skin: compounds that remain in the superficial cellular seats of the epidermis (for example, petrolatum and other fatty substances of mineral origin, silicones, dioxide titanium, zinc oxide, mica). * f Wr '"- *. ^? ? 'F"' .- *? 16 TABLE 1 Nature of (i; (2) .3) [4) Components Fluid lipids Oleic acid (XX) Triglycerides Vegetable oils Acetic linoleic acid (XX) (XXX) (XX or XXX in Esqualene (XX) petrolatum function oil used (XXX) 10 Concrete lipids Stearic acid (XX) Vaseline oil Palm acid palmitic (XX) (XX) white Cholesterol (XX) Beeswax (XXX) Cholesterol ester (XX) (XX) 15 Cholesterol sulfate (XX) I Ceramides (X) 17 TABLE 1 (Continued) Nature of (i) (2) (3) (4) Components Antio-oxidants Tocopherols (XX) Anti-radicals Citric acid (XX) Glutathione (XX) Riboflavonoids (X) (10 Dismutate superoxide (X) Palmitic acid (XX) Taurine Conservator (X) SCALE OF CUTANEOUS CITOCOMPATIBILITY X 0-1% XXX 10-50% XX '1-10% xxxx > fifty% i} . ß .. 18 TABLE 2 Nature of (1) (2); 3) (4) Components Glycolipids (XX) Lecithins (XX) Glycosylceramides (XX) 10 Tenso-active Stearate of. Soforolipids Lipoproteins lysine (XX) (XX) (XX) Arginine stearate (XX) Lysine oleate 15 (XX) _ $ 19 TABLE 2 (Continued) Nature of (1) (2) (3) (4; Components Thickeners Hyaluronic acid Mucopolis isa / formerly Chitin (XXX) (XX) (XX) DNA (XX) Starch (XX) Humectants Glycerin (XX) Urea (XX) Fructose (XX) Serine (XX) Glucose (XX) Antiseptics short chain fatty acids (X) Propol s (X) Lactoferrin / twenty TABLE 2 (Continued) Nature of (1) (2) (3) (4) Components Lactoperoxidase anticeptics (X) fifteen * 4 * _c * _ * J. ' twenty-one TABLE 3 Nature of (1) (2) (4) Components Dyes Vitamin B (X) Carotenoids (X) Flavines (X) Caramel (X) Filters and DNA (XX) Oxide blockers pyrimidic bases (X) solar (XX) Melanin oxide (XX) Zinc (XX) Perfumes Honey (X) 15 Minerals Sodium (XX) Calcium (XX) Magnesium (XX) J £? - - -i "* ._ ?, • _ * - i" ** * í ** "* v & *, '22 TABLE 3 (Continued) Nature of the (i: (2) (3) (4) Components Oligoelements Iron, Copper (X) Zinc (XX, Selenium (X) fifteen The compositions of some cosmetic products according to expiration are given below.

PRODUCT 1: Nourishing and moisturizing gel PHASE A: Nutritive composition (amino acids, vitamins, oligoele entos) c.b.p. 100 DNA sodium salt 2-5% Conservation system (glucose / glucose oxidase / lactoperoxidase) 0.9-1.1 PHASE B: Mucopolysaccharides 20-30% Superoxide dismutase 0.5-1% Citric acid 0.2-0.5% Trisodium citrate 0.5-2% PRODUCT 2: Refreshing and thickener spray PHASE A: Nutritive composition (amino acids, vitamins, trace elements) c.b.p. 100 Conservation system (glucose / glucose oxidase / lactoperoxidase) 0.9-1.1% PHASE B: Citric acid 0.2-0.5% Trisodium citrate 0.5-2-c PHASE C: Ramnosa 0.01-5% PRODUCT 3: Antiradical cream (1) for oily skin PHASE A: Tocopherol acetate 0.2-2 Stearic acid 3-5% Esqualene 2-7% Triglycerides 2-7% PHASE B: Water c.b.p. 100 L-arginine 1-2% Glicepna 1-2% Citric acid 0.2-0.5% Trisodium Citrate 0.5-2% PHASE C: Nutritional composition (Amino acids, vitamins,, __- trace elements) 45-55 i Conservation system (glucose / glucose oxidase / lactoperoxidase 0.9-1.1 15 Superoxide dismutase 0.5-1% PRODUCT 4: Cream (2) moisturizer for dry skin PHASE A: 20 Oleic acid 0.2-0.3% Palmitic acid 0.2-0.3% Behenic acid 0.2-0.3% Stearic acid 0.1-0.2% 25 Linoleic acid 0.1-0.2% Arachidic acid 0.05-0.1% Triglycerides 0.1-0.2% Cholesterol 0.9-1% Ester cholesterol 0.02-0.04% Phospholipids _L • O "" __-. D "6 Skalene 3-7% PHASE B: Water c.b.p. 100 L-arginine 1-2% Citric acid 0.2-0.5% Trisodium citrate 0.5-2% PHASE C: Nourishing composition (amino acids, vitamins, trace elements 45-55 Conservation system (glucose / glucose oxidase / lactoperoxidase) 0.9-1.1 5 PHASE D: Mucopolysaccharides 1-3 PRODUCT 5: Milk dema uillante des-sensibilizante PHASE A: Stearic acid: 2-5% Skull 2-7% Triglycerides 2-7% PHASE B: Water c.b.p. 100 L-arginine 1-2% Citric acid 0.2-0.5% Trisodium citrate 0.5-2% PHASE C: Nourishing composition (amino acids, vitamins, trace elements) 45-55% Superoxide dismutase ^ 0.5-1% Conservation system 0.9-1.1 Fucose 0.005-1 PRODUCT 6: PHASE A moisturizing lotion: Water c.b.p. 100 L-serine 1-3% Glycerin 1-2% Urea 1-3% Citric acid 0.2-0.5% Trisodium Citrate 0.5-2% PHASE B: Conservation system (glucose / glucose oxidase / lactoperoxidase) 0.9-1.1% PRODUCT 7: Dry oil PHASE A: Skalene 30-70% 20 Triglycerides 30-70 PRODUCT 8: Bioprotective sunscreen PHASE A:, i 25 Tocopherol acetate 0.2- 2 Stearic acid 3-5% Esqualene 2-7% Triglycerides 2-7% Titanium oxides 1-20% PHASE B: Water c.b.p. 100 L-arginine 1-2% Glycerin 1-2% Citric acid 0.2-0.5% Trisodium citrate 0.5-2% PHASE C: Conservation system (glucose / glucose oxidase / lactoperoxidase 0.9-1.1 5 PRODUCT 9: Regulating and anti-sensitizing cleansing milk PHASE A: Stearic acid 2-5 Esqualene 2-7% Triglycerides 2-7% PHASE B: Water c.b.p. 100 L-arginine 1-2% Glicepna 1-2% Citric acid 0.2-0.5% Trisodium Citrate 0.5-2% PHASE C: Conservation system (glucose / glucose oxidase / lactoperoxidase) 0.9-1.1% Phospholipids 2-10% PHASE D: Ramnosa 0.1-5% Fucosa 0.0005-lí The products according to the invention are for example in the form of a lotion, milk, cream, soap, etc., depending on their prescription or use, they are in stable topical, monophasic, biphasic, or three-phase form, for example.

It is noted that in relation to this date the best method known by the applicant to carry out the aforementioned invention is that which is clear from the present description of the invention.

Having described the invention as above, it is claimed as property in the following,

Claims (8)

1. cosmetic product or body hygiene, or dermo-therapeutic, which is characterized in that it comprises for at least 98% by weight, only cytocompatible biodermic constituents with the skin, interactively expressing together at least one topical bioactivity, identical or different from the bioactivity of at least one biodermic constituent, and which confers to said product a composition in stable topical galenic form, which excludes practically any non-biodermic excipient different from water.

2. Product according to claim 1, characterized in that said biodermic constituents are biomimetics with a skin component, and each have a weight content in said product, different from that of the same component in the skin.

3. Product according to claim 2, characterized in that a majority biodermic and biomimetic constituent is a constituent constituent of the skin, and in addition to being a biodermic and biomimetic constituent, is a skin nutrient.

4. Product according to claim 1, which is characterized in that each biodermic constituent is selected from the species or entities, biological, mineral, organic, or biochemical, which make up the epidermis or dermis.

5. Product according to claim 1, characterized in that at least one biodermic constituent is selected from the skin's nutrients.

6. Product according to claims 4 and 5, which is characterized in that the composition is completed by a non-biodermic constituent but cytocompatible with the skin.

7. Product according to claim 1, characterized in that it is in two-phase form, and for example constituted by a dispersion of water in oil, or oil in water.

8. Product according to claim 1, which is characterized in that the entirety of its composition is constituted by the cytocompatible biodermic constituents with the skin.