use of exopolysaccharides

专利摘要:
it is an exopolysaccharide from a bacterial strain for the treatment and / or care of the skin, mucous membranes, hair and / or nails, as well as their cosmetic and / or dermopharmaceutical compositions. in particular, it is intended for the aging of the skin and for the treatment and / or care of disorders, conditions and / or diseases that are the result of a lack or decrease in hydration.
公开号:BR112013013110B1
申请号:R112013013110
申请日:2011-11-30
公开日:2018-05-08
发明作者:Soley Albert；Courtois Anthony；Thollas Bertrand；Cebrian Juan；Delgado Raquel
申请人:Lipotec Sa；Polymaris Biotechnology；
IPC主号:

专利说明:

(54) Title: USE OF EXOPOLISACARIDES (51) Int.CI .: A61Q 19/00; A61Q 19/08; A61K 8/99; A61K 8/02; A61K 8/04; A61K 8/14; A61K 8/73; A61K 8/81; A61K 47/36; A61K 9/00; A61K 8/06 (30) Unionist Priority: 11/30/2010 ES P201031775 (73) Holder (s): LIPOTEC, S.A .. POLYMARIS BIOTECHNOLOGY (72) Inventor (s): ANTHONY COURTOIS; BERTRAND THOLLAS; RACHEL DELGADO; JUAN CEBRIAN; ALBERT SOLEY
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USE OF EXOPOLISACARIDE FIELD OF THE INVENTION
This invention relates to an exopolysaccharide (EPS) excreted by the bacterial strain CNCM I-4150 of the species
Pseudoalteromonas sp. This invention also relates to the use of this exopolysaccharide in cosmetic or dermopharmaceutical compositions for the treatment and / or care of the skin, mucous membranes, hair and / or nails.
DESCRIPTION
The skin, mucous membranes, hair and / or nails constitute a physical barrier between the organism and its environment. The skin is composed of two tissues: the epidermis and the dermis. The epidermis is the outermost layer of the skin, which is impermeable and therefore provides protection against external agents. It is a keratinized multi-stratified epithelium that is continually renewing itself. Keratinocytes constitute the main population of cells in the epidermis and are responsible for maintaining the epithelial structure due to its function as a barrier.
The epidermis is composed of several cell layers; the basal extract is the deepest layer connected to the dermis at the dermis-epidermis junction and is composed of non-differentiated cells. Over time, these cells differentiate and migrate towards the surface of the epidermis, which constitutes the different layers. The topmost layer formed is the horny extract, which is composed of corneocytes. The corneocytes are keratin, rich cells that are able to retain water and are surrounded by a protein and a lipid barrier. There are 10 to 30 layers of stacked corneocytes, which are connected together by protein bridges called desmosomes. The resulting structure is a natural physical barrier to the skin that retains water. The
Petition 870180014816, of 23/02/2018, p. 6/15
2/49 corneocytes are dead cells that are eliminated by flaking, and that, in the absence of water, do not normally decay, which leads to an appearance of dry, dense and rigid skin. The loss of the superficial extract caused by flaking is compensated by the migration of cells from the basal extract towards the surface of the epidermis. This is, therefore, a process of continuous skin renewal that helps to keep it soft.
Corneal cells contain a protein called filaggrin that binds to keratin proteins. Philagrin is located on the outside of the corneocytes, while keratin, which is capable of retaining water, remains on the inside of the corneocytes. When the skin's moisture content decreases, specific proteolytic enzymes in the horny extract cause the breakdown of philagrin into free amino acids to control the skin's osmotic pressure and the amount of water it contains. All of these free amino acids are produced together with other physiological chemicals such as lactic acid, pyrrolidone, carboxylic acids, urea and other salts present in the horny extract called natural moisturizing factors, which are responsible for keeping the skin moist and supple by attracting and retain water. The water content in the horny extract under physiological conditions is usually close to 30%. Natural hydration factors are water-soluble intercellular substances that undesirably can easily escape from the skin, which, therefore, decreases its concentration, which causes water not to be so easily trapped in the epidermis.
The dermis is the layer of skin located under the epidermis and firmly connected to it. It is an elastic support tissue of mesodermal origin that consists mainly of fibroblasts and an extracellular matrix of fibrous proteins (collagen and elastin) and non-protein
3/49 fibrous (proteoglycans and glycoproteins). The dermis, which is essentially rich in hyalauronic acid and polysaccharides, works as a water reserve, retaining the water brought to it by blood vessels. It stores water like a sponge and passes water to the epidermis when needed, along with other nutritional substances that the epidermis may also need. Therefore, the dermis has a fundamental role in the development and differentiation of the epidermis. Fibroblasts and extracellular matrix also influence the mechanical properties of the skin, in particular, its elasticity, tone and firmness, as well as the density of the skin.
The skin can lose water in two ways: mainly by perspiration, which is an active phenomenon caused by the sweat glands to regulate the temperature of the skin and also, although in a minimal way, by the passive evaporation of water through the epidermis. This passive evaporation or insensitive water loss occurs with a kinetics that is the reflection of a balance between the water content of the epidermis and the relative humidity of the surroundings and its measurement is a reflection of the integrity of the skin barrier. For example, under normal conditions, the loss of insensitive water is normally 5 g / m ² / hour, but in atopic children and areas of dry skin without eczema, the loss of insensitive water can reach 13 to 18 g / m ² / hour.
The integrity of the skin barrier or the function of the skin barrier also depends on the density of the horny extract. The horny extract was compared to a brick wall, in which keratinocytes or corneocytes (bricks) are essentially the portion of non-continuous, fully differentiated proteins, which are incorporated into a continuous matrix of specialized lipids (mortar). Lipids provide the essential element of the water barrier and
4/49 corneocytes protect against continuous abrasion by chemical or physical injuries.
Hydration is an essential factor in maintaining youth and skin vitality for any age group. When the amount of water is insufficient, the horny extract loses elasticity and experiences a sensation of compressibility, a phenomenon that is commonly referred to with the term dry skin. However, properly hydrated skin is soft, flexible and looks shiny and young.
Healthy skin is one that maintains optimal water concentration levels. The presence of water in the dermis and epidermis favors the group of regenerative mitotic reactions of the skin cells, which contribute to the regeneration of our skin. An optimal water concentration is decisive for the flexibility of the skin and, as a consequence, for the prevention of the appearance of wrinkles caused by age and its treatment and for the healing of small wounds.
However, skin homeostasis can be affected by certain physiological factors (age, menopause, hormonal changes, lack of nutrition and lack of hydration, xerosis, etc.) or environmental factors (ultraviolet radiation, pollution, stress, hypoxia, infectious agents, dry, irritating conditions, etc.). These factors cause a decrease in the assimilation and fixation of water on the skin that quickly becomes obvious on the skin surface through unmistakable signs such as dry skin or a tendency to irritation. This leads to decreased regeneration of the epidermis (the cells in the basal extract have less dividing activity, proteins in the skin are denatured and disturbed and / or the protective intercellular lipid layers are eliminated and the cohesion between cells is reduced), which leads to a decrease in skin hydration. Environmental factors
5/49 also causes deregulation of hair and nail hydration, both of which become rigid, fragile and brittle.
The cosmetic and dermopharmaceutical industry has gone through considerable efforts to develop compositions that are capable of maintaining the water balance of the skin, mucous membranes, hair and / or nails, in order to improve its appearance, as well as its protective and its function as a barrier. One of these ingredients is hyalauronic acid; a glycosaminoglycan without sulfate from the extracellular matrix formed by D-glucuronic acid and D-2Vacetylglycosamine. Hyalauronic acid is capable of retaining water in the skin, helping to keep the skin more hydrated, elastic and with a more uniform skin surface. The amount of hyalauronic acid that the skin synthesizes dramatically reduces with age (Matuoka et al. Aging, 1989, 1 (1): 47 to 54) and this is the cause of mature skin's tendency to dry out, lose elasticity and form wrinkles . Hyalauronic acid plays an important role in preventing and reducing both wrinkles and expression lines; one of the most common strategies employed by the cosmetic and dermopharmaceutical industry for the treatment of wrinkles is the administration of hyalauronic acid both topically and subcutaneously due to its ability to absorb water and, therefore, fill the crease inside the skin.
0 hyalauronic acid it's found at matrix extracellular of human tissues and animals but O same exists in certain bacteria strains such as at of genre Streptococcus and Pasteurella, which produce O same > by
emulation of tissues from animal tissues as a way to protect against attacks by the immune system of the animals that they infect, since they are pathogenic microorganisms. Therefore, the production of hyalauronic acid is possible from the fermentation of bacteria
6/49 which produces the same naturally. In addition, it should be noted that this production is also possible through other genetically modified bacteria.
Just as certain bacteria produce hyalauronic acid, there are also bacteria that can produce other sugars or exopolysaccharide polymers. The existence of exopolysaccharides has been known since the 1970s, they are produced by species of bacteria that live in ecosystems known for their extreme conditions. The production of exopolysaccharides by the bacteria that live in these ecosystems is mainly related to survival functions (Raguénès et al. J Appl Microbíol., April 1997, 82 (4): 422 to 30).
The different exopolysaccharides described in the prior art that have been used for cosmetic and / or dermopharmaceutical purposes, such as the exopolysaccharide produced by a strain of bacteria of the genus Pseudomonas described in Patent EP0534855B1 that is used as a thickening, gelling and / or texturing agent. In addition, patent application FR2871476A1 describes the GY785 strain of hydrothermal origin of the genus Alteromonas that produces an exopolysaccharide that can be used as a healing agent; EP0987010B1 describes an exopolysaccharide produced by a mesophilic bacterium of hydrothermal origin that improves the skin's defense system and patent application US2010 / 009931 describes the exopolysaccharide produced by a microalgae strain of the genus Porphyridium as a surfactant, which also improves the firmness, elasticity and tone of the skin. American patent application US2009 / 069213A1 also describes the microalgae strain Porphyridium sp. which produces a polysaccharide that has anti-wrinkle and moisturizing properties. The US6344346B1 patent also describes
7/49 cosmetic compositions with moisturizing properties caused by a polysaccharide of natural origin excreted by a bacterium of the genus Rhizobium.
Another exopolysaccharide that has proven to have numerous beneficial properties for the skin is the exopolysaccharide described in application WO2009 / 127057 produced by strains of the bacterial species Staphylococcus epidermídis and Staphylococcus aureus. After applying a cosmetic composition of this exopolysaccharide, the hydration and morphology of the horny extract improves and the skin peels off.
Finally, patent application JP2003-313131 should also be mentioned since it describes a polysaccharide sulfate produced by a strain of Alteromonas sp. SN-1009 (FERM BP-5747) with anti-wrinkle properties.
Surprisingly, the depositor of this invention found a new alternative to the exopolysaccharides described in the prior art based on a new exopolysaccharide excreted by the non-hydrothermal bacterial strain Pseudoalteromonas sp., Deposited with the CNCM under the number 1-4150 according to the Budapest Treaty, which improves the hydration of the skin, mucous membranes, hair and / or nails and prevents and / or reduces wrinkles.
DETAILED DESCRIPTION OF THE INVENTION
This invention relates to the cosmetic and / or dermopharmaceutical use of the exopolysaccharide excreted by the bacterial strain CNCM 1-4150 of the species Pseudoalteromonas sp. Surprisingly, the inventors of this invention have found that the aforementioned exopolysaccharide is an alternative to hyalauronic acid that solves problems caused by poor hydration of the skin, mucous membranes, hair and / or nails and balances the skin surface.
Definitions
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To facilitate the understanding of this invention, the meanings of some terms and expressions as used in the context of the invention are included.
In the context of this invention, the skin is understood to be the layers that comprise it, from the uppermost layer or horny extract to the lower layer or hypodermis, both inclusive. These layers are composed of different types of cells such as keratinocytes, fibroblasts, melanocytes and / or adipocytes, among others. In the context of this invention, the term skin includes the scalp.
In the context of this invention, skin care, mucous membranes, hair and / or nails comprises the prevention of disorders and / or diseases of the skin, mucous membranes, hair and / or nails.
In the context of this invention, the term aging refers to changes experienced by the skin with age (chronological aging) or by exposure to the sun (photoaging) or to environmental agents such as tobacco smoke, extreme cold, hot or windy conditions, contaminants or chemical pollutants and that includes all visible and / or perceptible changes through external touch such as, but not restricted to the development of discontinuities in the skin such as wrinkles, fine lines, furrows, irregularities or roughness, increased pore size, loss of elasticity, loss of firmness, loss of smoothness, loss of the ability to recover from deformation, sagging skin such as sagging cheeks, the appearance of bags under the eyes or the appearance of a double chin, among other changes in skin color such as marks, browning, bags under the eyes or the appearance of hyperpigmented areas such as age spots or freckles, among others, anomalous association, hyperkeratinization, elastosis, keratosis, hair loss, bark skin
9/49 orange, loss of collagen structure and other histological changes in the horny extract, dermis, epidermis, vascular system (for example, the appearance of spider veins or telangiectasia) or those tissues close to the skin, among others. The term photoaging groups the set of processes due to prolonged exposure of the skin to ultraviolet radiation that result in premature aging of the skin and has the same physical characteristics of aging, such as and not restricted to, laxity, flaccidity, changes in color or irregularities in pigmentation, abnormal and / or excessive keratinization.
The strain that produces the exopolysaccharide in this invention was deposited according to the Budapest Treaty, on September 4, 2009, in the Collection Nationale de Culture de Microorganismes (CNCM), Pasteur Institute, 28 rue du Docteur Roux, 75724 Paris, France, under the code CNCM 1-4150.
Therefore, a first aspect of this invention concerns the exopolysaccharide of bacterial strain CNCM 1-4150 from Pseudoalteromonas sp. for the treatment and / or care of the skin, mucous membranes, hair and / or nails.
In a particular modality, the treatment and / or care of the skin, mucous membranes, hair and / or nails is a treatment and / or prevention of
Preferably, treatment and / or aging is a treatment and / or prevention of skin wrinkles and / or skin dryness.
In another modality in particular, the treatment and / or care of the skin, mucous membranes, hair and / or nails is a treatment and / or care for conditions, disorders and / or diseases that are a result of the lack or reduction of skin hydration. , mucous membranes, hair and / or nails. Preferably, the conditions, disorders and / or diseases are aging. prevention of
10/49 selected from the group formed by dry skin, xerosis, hyperkeratosis, reactive hyperkeratosis, palmar and plantar hyperkeratosis, calluses and calluses, actinic keratosis, non-actinic keratosis, atopic dermatitis, contact eczema, seborrheic dermatitis, dandruff, seborrheic dermatitis neonatal in babies, acne, rosacea, mole, ichthyosis, psoriasis, parakeratosis, pityriasis, lichen planus, palmoplantar keratoderma, chapped lips, vaginal dryness, dry eye, dry hair, brittle hair and nails.
In another particular embodiment, the treatment and / or care of the skin, mucous membranes, hair and / or nails is performed by topical, transdermal, oral or parenteral application of the exopolysaccharide of the invention. In the context of this invention, the term parenteral includes nasal, auricular, ophthalmic, rectal, urethral, vagina routes, subcutaneous, intradermal, intravascular injections such as intravenous, intramuscular, intraocular, intradorsal, intramedullary, intracerebral, intrameningeal, intraarticular, intrahepatic injection. , intrathoracic, intratracheal, intrathecal and intraperitoneal, as well as any other similar infusion or injection techniques.
In another particular embodiment, the exopolysaccharide can be obtained by fermenting the strain of Pseudoalteromonas sp. CNCM 1-4150 in a suitable culture medium, agitated and aerated conventionally to synthesize and secrete the exopolysaccharide in the culture medium. The fermentation to produce the exopolysaccharide of this invention can be carried out in a stirred and aerated medium at a temperature between 20 ° C and 32 ° C, preferably at 29 ° C, the medium having a pH between 6.5 and 9, preferably about 7.5, adjusting the same if necessary during fermentation. The fermentation duration is between 30 to 120 hours, intravitreal, intracranial, intracorneal, intracervical, between the
120
11/49 preferably between 48 to 96 hours.
In a particular embodiment, in the fermentation of the bacterial strain of Pseudoalteromonas sp. of the invention, exogenous sugars can be used as a carbon source such as and not restricted to, galactose, glucose, mannose, tonsillin, cellobiose, maltose, starch, glycogen, lactose, mixtures thereof and / or extracts containing mixtures of these sugars . In particular, an exogenous supply of glucose from 2 to 40 g / L is provided, preferably from 15 to 25 g / L. Methods of incorporating sugar to produce different polysaccharides are described in the prior art, for example and not restricted to, in documents: WO 98/38327, Raguénès et al. Int. J. Syst. Bact., 1997, 47: 989 to 995 and Rougeaux et al., Carbohydrates. Res., 1999, 322: 40 to 45.
In another particular modality, mineral salts are provided for the fermentation culture of the bacterial strain CNCM 1-4150 of the species Pseudoalteromonas sp. For example and not restricted to, they are selected from salts that provide the ions Na ⁺ , K ⁺ , NH4 ⁺ , Ca ²⁺ , Mg ²⁺ , PO4 ^3- , SO ₄ ² ', Cl ”, CO ^{3 2} ” or oligo elements such as Cu, Mn, Fe and Zn.
In another particular embodiment, the method of isolation and purification of the exopolysaccharide is carried out by methods known to the person skilled in the art such as centrifugation, filtration, ultrafiltration and dialysis. Preferably, ultrafiltration and dialysis are performed with a polyethersulfan membrane that retains molecules with a molecular weight greater than 100,000 Da.
In a particular embodiment, this invention relates to the native exopolysaccharide as well as any chemical modification known to the person skilled in the art such as sulfatization, methylation and / or acetylation or the formation of exopolysaccharide-metal complexes.
In a preferred embodiment, the molecular weight of the
12/49 polysaccharide is modified by radical depolymerization which results in a polymer with a molecular weight between 100 and 800,000 Daltons, preferably a molecular weight between 100 and 500,000 Daltons and, more preferably, a molecular weight between 100 and 100,000 Daltons. Depolymerization methods are known in the prior art, for example and not restricted to, those described in Volpi et al. Anal. Biochem., 1992, 200: 100 to
107.
In a preferred embodiment, the exopolysaccharide excreted by the bacterial strain of the species of Pseudoalteromonas sp. CNCM 1-4150 is characterized by the production of at least four different neutral monosaccharides and two acid monosaccharides. The neutral monosaccharides are preferably mannose, glucose, galactose and W-acetylglycosamine. The acid monosaccharides are preferably glycuronic acid and galacturonic acid. More preferably, the exopolysaccharide of this invention produces a composition by weight of 3% to 12% of mannose, 12% to 34% of glucose, 12% to 34% of glucuronic acid, 2% to 20% of galacturonic acid, 12% to 34% galactose and 2% to 18% Nacetylglycosamine, with the proviso that the sum of the percentages does not exceed 100%. Even more preferably, the exopolysaccharide produces a composition by weight of 4% to 10% of mannose, 17% to 29% of glucose, 17% to 29% of glucuronic acid, 4% to 18% of galacturonic acid, 17% to 29 % galactose and 4% to 14% de-acetylglycosamine. Even more preferably, the exopolysaccharide produces a composition by weight of 5% to 9% mannose, 20% to 26% glucose, 20% to 26% glucuronic acid, 9% to 15% galacturonic acid, 20% to 26 % galactose and 7% to 12% W-acetylglycosamine. Optionally, the exopolysaccharide also contains rhamnose.
A second aspect of this invention concerns a
13/49 cosmetic or dermopharmaceutical composition characterized in that it comprises a cosmetic or dermopharmaceutical effective amount of the exopolysaccharide of this invention and at least one excipient, adjuvant and / or ingredient acceptable in a cosmetic and / or dermopharmaceutical manner.
The effective cosmetic or dermopharmaceutical amount of the exopolysaccharide in the composition of the invention to be administered, as well as its dosage, will depend on numerous factors including age, condition of the patient, the nature or severity of the condition, disorder or disease to be treated and / or care, the route and frequency of administration and the nature, in particular, of the exopolysaccharide to be used.
Effective in a cosmetic or dermopharmaceutical way, it should be understood as being a non-toxic amount, but sufficient of the exopolysaccharide to provide the desired effect. The exopolysaccharide of the invention is used in the cosmetic or dermopharmaceutical composition of this invention in effective concentrations in a cosmetic or pharmaceutical manner to obtain the desired effect;
preferably, in relation to the total weight of the composition,
20% (by weight) between 0.00000001% (by weight) and preferably between 0.000001% (by weight) and 20% (by weight), more preferably between 0.0001% (by weight) and 10% (in weight) and even more preferably between 0.0001% (by weight) and 5% (by weight).
In a particular embodiment, the exopolysaccharide of the invention can also be incorporated into cosmetic and / or dermopharmaceutical delivery systems and / or extended release systems.
The term delivery systems refers to a cosmetic and / or dermopharmaceutical suitable carrier such as a diluent, adjuvant, excipient, vehicle or
14/49 additives with which the exopolysaccharide of the invention is administered. Such delivery systems are well known in the prior art and can be used, for example, to improve the definitive formula with regard to organoleptic properties, skin penetration and the bioavailability of the active ingredient. Such cosmetic and / or dermopharmaceutical vehicles can be liquids, such as water, oils or surfactants, including those of petroleum, animal, vegetable or synthetic origin, such as and not restricted to, peanut oil, soy oil, mineral oil, oil sesame, castor oil, polysorbates, sorbitan esters, maltoside sulphates, glycosides, poloxamers, ether, sulphates, betaines, fatty alcohols, nonoxynols, polyoxyethylenes, polyethylene glycols, dextrose, glycerol, digitonin and the like.
The term continuous release is used in a conventional sense related to a composition delivery system that provides the gradual release of this composition over a period of time and preferably, although not necessarily, with relatively constant levels of composition release over a period of time. a period of time.
Examples of delivery or delivery systems are liposomes, mixed liposomes, niosomes, etosomes, milliparticles, microparticles, nanoparticles and solid lipid nanoparticles, nanostructured lipid supports, sponges, cyclodextrins, vesicles, micelles, mixed surfactant micelles, phospholipid micelles. , millispheres, microspheres and millicapsules, microcapsules and microemulsions and nanoemulsions, which can be added to obtain greater penetration of the active principle and / or improve its pharmacokinetic properties and prolonged elasmosomes, nanospheres, nanocapsules, lipospheres, as well as
15/49 pharmacodynamics. The delivery or prolonged release systems are liposomes, mixed micelles surfactant phospholipids and microemulsions, more preferably water-in-oil microemulsions with an internal reverse micelle structure.
Extended-release systems can be prepared by methods known in the prior art and the compositions containing them can be administered, for example, by topical or transdermal administration, which includes adhesive bandages, non-adhesive bandages, occlusive bandages and microelectric bandages or by systemic administration, such as and not restricted to, orally or parenterally, which includes nasal, rectal or injection or subcutaneous implant or implant or direct injection in a specific body part and, preferably, should release a relatively constant amount of the exopolysaccharide of the invention . The amount of exopolysaccharide contained in the extended release system will depend, for example, on where the composition is to be administered, on the kinetics and duration of release of the exopolysaccharide of the invention, as well as on the nature of the condition, disorder and / or disease to be treated and / or care.
The composition containing the exopolysaccharide of this invention can also be absorbed into a solid organic polymer or solid mineral support, such as and not restricted to, talc, bentonite, silica, starch or maltodextrin, among others.
Compositions containing the exopolysaccharide of the invention can also be incorporated into tissues, non-woven fabrics or medical devices that are in direct contact with the skin, thereby releasing the exopolysaccharide of the invention or by biodegradation of the tissue binding system, non-woven fabric tissue or medical device, or due to
16/49 friction between them and the body, due to body moisture, skin pH or body temperature. In addition, fabrics and non-woven fabrics can be used to make garments that are in direct contact with the body.
Examples of fabrics, non-woven fabrics, clothing, medical devices and mechanisms for immobilizing the exopolysaccharide to them, among which are the delivery systems and / or the prolonged release systems described above, can be found in the literature and are known in the art previous (Schaab CK 1986 Impregnating Fabrics With Microcapsules, HAPPI May 1986; Nelson G. Int. J. Pharm. 2002, 242: 55 to 62 / Hipler UC y Elsner P. 2006, Biofunctional Textiles and the Skin, Curr. Probl. Dermatol v.33,., S. Karger AG editions, Basel, Switzerland; Malcom RK et al. J. Cont. Release, 2004, 97: 313 to 320). Preferred fabrics, non-woven fabrics, clothing and medical devices are bandages, gauze, t-shirts, socks, pants, underwear, belts, gloves, diapers, sanitary napkins, adornments, covers, flannels, adhesive bandages, non-adhesive bandages, occlusive bandages , microelectric bandages and / or face masks.
The cosmetic or dermopharmaceutical compositions containing the exopolysaccharide of this invention can be used in different types of compositions for topical or transdermal application, optionally including excipients acceptable in a cosmetic and / or dermopharmaceutical manner necessary to form the desired form of administration.
Compositions for topical or transdermal application can be produced in any solid, liquid or semi-solid formula. Therefore, such topical or transdermal compositions are, for example, and not restricted to, creams, multiple emulsions such as and not restricted to, oil and / or silicone in water emulsions, water in oil emulsions and / or
17/49 silicone, water / oil / water or water / silicone / water emulsions, and oil / water / oil or silicone / water / silicone emulsions, microemulsions, emulsions and / or solutions, liquid crystals, anhydrous compositions, aqueous dispersions, oils, milks, balms, foams, aqueous or oily lotions, aqueous and oily gels, cream, hydroalcoholic solutions, hydroglycolic solutions, hydrogels, ointments, serum, soaps, shampoos, conditioners, facial masks, hair sprays, serum, films of polysaccharides, ointments, mousses, perfume ointments, pastes, powders, bars, pencils and sprays or aerosols (sprays) that include let dry or rinse formulas. These formulas are applied topically or transdermally to local areas of the skin, mucous membranes, hair and / or nails and can be incorporated using techniques known to the person skilled in the art in different types of solid accessories, such as and not restricted to, bandages , gauze, t-shirts, socks, pants, underwear, belts, gloves, diapers, sanitary napkins, adornments, covers, flannels, adhesive bandages, non-adhesive bandages, occlusive bandages, microelectric bandages and / or facial masks or they can be incorporated in different makeup products such as makeup foundation creams, such as fluid foundation creams and compact foundation creams, makeup lotions or removers, makeup remover milks, eye concealers, eye shadows, lipsticks, lip balms, lip gloss and powders among others.
The cosmetic or dermopharmaceutical compositions of the invention may include agents that increase the percutaneous absorption of the exopolysaccharide of this invention, for example and not restricted to, dimethylsulfoxide, dimethylacetamide, dimethylformamide, surfactants, azone (1dodecylazacycloheptane-2-one), alcohol, urea, urea
18/49 acetone, propylene glycol or polyethylene glycol, among others. In addition, the cosmetic or dermopharmaceutical compositions of this invention can be applied to local areas to be treated by mechanisms of iontophoresis, sonophoresis, electropermeabilization, microelectric bandages, mechanical pressure, osmotic pressure gradient, occlusive cure, microinjections or needle-free injections by pressure mechanisms , such as oxygen pressure injections or any combination thereof, to obtain greater penetration of the inventive exopolysaccharide. The area of application will be determined by the nature of the condition, disorder and / or disease to be treated and / or cared for.
In addition, the cosmetic or dermopharmaceutical compositions containing the exopolysaccharide of this invention can be used in different types of formulas for oral administration, preferably in the form of cosmetics or oral medication, such as and not restricted to, capsules that include gelatin capsules, soft capsules, hard capsules, tablets, which include sugar-coated tablets, powders, granules, chewing gum, solutions, suspensions, emulsions, syrups, polysaccharide films, jellies or gelatines and any other form known to the person skilled in the art. In particular, the exopolysaccharide of the invention can be incorporated into any form of functional food or fortified food, such as and not restricted to, compact or non-compact diet bars or powders. These powders can be dissolved in water, carbonated drinks, dairy products, soy derivatives or can be incorporated into diet bars. The exopolysaccharide of this invention can be formulated with excipients and adjuvants common to oral compositions or food supplements, such as and not restricted to, fatty components, aqueous components, humectants, preservatives, texturing agents, condiments,
19/49 aromas, antioxidants and paints common in the food industry.
Cosmetic or dermopharmaceutical compositions containing the exopolysaccharide of the invention can also be administered by the topical or transdermal route, as well as by any other appropriate route, for example, parenteral or oral route, for which they will include the pharmaceutically acceptable excipients necessary for the formula for the desired administration of the exopolysaccharide.
Among the excipients acceptable in cosmetic or dermopharmaceutical form, adjuvants and / or ingredients contained in the compositions acceptable in cosmetic or dermopharmaceutical form described in this invention are additional ingredients normally used in compositions for the treatment and / or care of skin, mucous membranes, hair and / or nails such as and not restricted to, acetylcholine receptor cluster inhibiting agents, muscle contraction inhibiting agents, anticholinergic agents, elastase inhibiting agents, matrix metalloproteinase inhibiting agents, melanin synthesis inhibiting or stimulating agents, bleaching agents or depigmenters, pro-pigmenting agents, tanning agents, anti-aging agents, NO synthase inhibiting agents, 5a reductase inhibiting agents, lysyl- and / or prolyl hydroxylase inhibiting agents, antioxidants, free radical scavengers and / or counter agents air pollution, sequ reactive carbonyl species estrantes, anti-glycation agents, antihistamines, antiviral agents, antiparasitic agents, emulsifiers, emollients, organic solvents, liquid propellants, skin conditioners such as humectants, moisture-retaining substances, alpha hydroxy acids, beta hydroxy acids, creams moisturizers, hydrolytic enzymes
20/49 epidermals, vitamins, amino acids, proteins, pigments or dyes, inks, coagulating polymers, thickeners, surfactants, softening agents, anti-wrinkle / anti-aging agents, agents capable of reducing or treating bags under the eyes, exfoliating agents, desalting agents, keratolytic agents, antimicrobial agents, antifungal agents, fungistatic agents, bactericidal agents, bacteriostatic agents, agents stimulating the synthesis of macromolecules and / or capable of inhibiting or preventing their degradation, such as, for example, stimulating agents of collagen synthesis, stimulating agents elastin synthesis agents, decorin synthesis stimulating agents, laminin synthesis stimulating agents, defensin synthesis stimulating agents, aquaporin synthesis stimulating agents, hyaluronic acid synthesis stimulating agents, fibronectin synthesis stimulating agents, stimulating agents synthesis of sirtuin, stimulating agents chaperone synthesis agents, lipid synthesis stimulating agents and components of the horny extract (ceramides, fatty acids, etc.), collagen degradation inhibiting agents, elastin degradation inhibiting agents, serine inhibiting agents
proteases such as cathepsin G, agents stimulants gives proliferation in fibroblast, agents stimulants gives proliferation in keratinocytes, agents stimulants gives proliferation in adipocytes, agents stimulants gives proliferation in melanocytes, agents stimulants gives differentiation in keratinocytes, agents stimulants gives differentiation in adipocytes, agents inhibitors in
acetylcholinesterase, skin relaxing agents, glycosamino glycan synthesis stimulating agents, antihyperkeratosis agents, comedolytic agents, antipsoriasis agents, DNA repair agents, protective agents
21/49 of DNA, stabilizers, anti-itch agents, agents for the treatment and / or care of sensitive skin, stabilizing agents, redensifying agents, restructuring agents, anti-stretch marks, binding agents, sebum production regulating agents, lipolytic agents or agents lipolysis stimulants, anti-cellulite agents, antiperspirant agents, healing stimulating agents, supporting healing agents, stimulating reepithealization agents, supporting reepithealization agents, cytokine growth factors, calming agents, anti-inflammatory and / or analgesic agents, anesthetic agents , agents acting on capillary circulation and / or microcirculation, angiogenesis stimulating agents, vascular permeability inhibiting agents, venotonic agents, agents that act on cellular metabolism, agents to improve the dermis-epidermis junction, agents that promote hair growth, retarding or inhibiting agents capillary growth r, agents that slow hair loss, preservatives, perfumes, chelating agents, plant extracts, essential oils, marine extracts, agents obtained from a biofermentation process, mineral salts, cell extracts and sunscreens (organic photoprotective agents or active minerals against ultraviolet rays A and / or B) among others, provided that they are physically and chemically compatible with the other components of the composition and, in particular, with the exopolysaccharide contained in the composition of this invention. Furthermore, the nature of these additional ingredients must not unacceptably alter the benefits of the exopolysaccharide of this invention. The nature of these additional ingredients can be synthetic or natural, such as plant extracts, or obtained through a biofermentation process or from a combination of a process
22/49 synthetic and a biotechnological process. Additional examples can be found in the CTFA International Cosmetic Ingredient Dictionary & Handbook, 12th Edition (2008). In the context of this invention, the biotechnological process is understood to be any process that produces the active ingredient or part of it in an organism or part of it.
In a particular modality, the anti-wrinkle and / or anti-aging agent is selected, for example, and not restricted to, from the group formed by extracts of Vitis vinifera, Rosa canina, Curcuma longa, iris pallida, Theobroma cacao, Ginko biloba, Leontopodium Alpinum or Dunaliella salina, Matrixyl® [INCLUDES: Palmitoil Pentapeptide-4], Matrixyl 3000® [INCLUDES: Palmitoil Tetrapeptide-7, Palmitoyl Oligopeptide], Essenskin ™ [INCLUDES: Calcium Hydroxyethionine], Renovage [INCLUDES: Teprenone] or Dermax [INCLUDES: Palmitoil Oligopeptide] sold by Sederma / Croda, Vialox® [INCLUDES: Pentapeptide-3], Syn®-Ake® [INCLUDES: Benzylamide Diaminetide Dipeptide Diaminobutiroil], Syn®Coll [INCLUDES: Palmitoil Tripeptide-5], Fitaluronate [INCLUDES: Carob Gum (Ceratonia Siliqua)] or Preregen® [INCLUDES: Glycine Soy Protein (Soya bean), Oxidorreductases] marketed by Pentapharm / DSM, Myoxinol ™ [INCLUDES: Hydrolyzed Hibiscus Extract], Syniorage ™ [INCL : Acetyl Tetrape peptide-11], Dermican ™ [INCLUDES: Acetyl Tetrapeptide-9] or DN-AGE ™ LS [INCLUDES: Cassia Alata leaf extract] sold by Laboratoires Sérobiologiques / Cognis, Algisum C® [INCLUDES: Methylsilanol Manuronate] or Hydroxyprolysilane CN® [INCLUDES: Methylsilanol Hydroxyprolinate] marketed by Exsymol, Argireline® [INCLUDES: Acetyl Hexapeptide-8], SNAP-7 [INCLUDES: Acetyl Heptapeptide-4], SNAP-8 [INCLUDES: Acetyl Octapeptide3], Leuphasyl® INCLUDES: Pentapeptide-18], Aldenine® [INCLUDES:
23/49
Hydrolyzed Wheat Protein, Hydrolyzed Soy Protein,
Diaminopropionyl Tripeptide-10 from yeast
Tripeptide-1], Preventhelia [INCLUDES:
Tripeptide-33], Decorinyl ™ [INCLUDES:
Citrulline], Trylagen® [INCLUDES: Extract
Pseudoalteromonas, Hydrolyzed Wheat Protein, Hydrolyzed Soy Protein, Tripeptide-10 Citrulline, Tripeptide-1], Eyeseryl® [INCLUDES: Acetyl Tetrapeptide-5], Peptide AC29 [INCLUDES: Acetyl Tripeptide-30 Citrulline], Lipochroman-6 : Dimethylmethoxy Cromanol], Chromabright ™ [INCLUDES:
Dimethylmethoxy Cromanyl Palmitate], Serilesine® [INCLUDES: Hexapeptide-10], Antarcticine® [INCLUDES: Pseudoalteromonas yeast extract], Vilastene ™ [INCLUDES: Lysine HC1,
Lecithin, Tripeptide-10 Citrulline], dGlyage ™ [INCLUDES: Lysine HCl, Lecithin, Tripeptide-9 Citrulline], Relistase ™ [INCLUDES: Acetillarginyltriptofil Diphenylglycine],
Thermostressine ™ [INCLUDES: Acetyl Tetrapeptide-22] or
Inyline ™ [INCLUDES: Acetyl Hexapeptide-30] marketed by Lipotec, Kollaren® [INCLUDES: Tripeptide-1, Dextran] marketed by Institut
Cellulaire / Unipex, Collaxyl® IS
Europeen de Biologie [INCLUDES: Hexapeptide-9],
Laminixyl IS ™ [INCLUDES: Heptapeptide], Orsirtine ™ GL [INCLUDES: Oryza Sativa (Rice) Extract], DOrientine ™ IS [INCLUDES: Phoenix Dactylifera Seed Extract (Date)], »> TM
Phytoqumtescine
Monococcum)] or [INCLUDES: Corn Extract (Triticum
Quintescine ™ IS [INCLUDES: Dipeptide-4] marketed by VIncluience / ISP, BONT-L-Peptide [INCLUDES: Palmitoil Hexapeptide-19] marketed by Infinitec Activos, Deepaline ™ PVB [INCLUDES: Palmitoil Hydrolyzed Wheat Protein] or Sepilift® DPHP [INCLUDES: Dipalmitoil
Hydroxyproline] marketed by Seppic, Gatuline® Expression [INCLUDES: Acmella Oleracea Extract], Gatuline® In-Tense [INCLUDES: Spilanthes Acmella Flower Extract] or Gatuline® Age Defense 2 [INCLUDES: Seed Extract
24/49 marketed by Algae Extract]
ChroNOline
TM [INCLUDES: Acetyl
Juglans Regia (Common Walnut)]
Gattefossé, Thalassine ™ [INCLUDES: marketed by Biotechmarine,
Caprooil Tetrapeptide-3] or Thymulen-4 [INCLUDES:
Tetrapeptide-2] marketed by Atrium Innovations / Unípex Innovations, EquiStat [INCLUDES: Pyrus Malus Fruit Extract, Glycine Soybean Extract] or Juvenile [INCLUDES: Caprylic Triglyceride, Retinol, Ursolic Acid, Phytomenadione] by Coletica / Engelhard / BASE, Ameliox [INCLUDES: Carnosine,
Tocopherol, Silybum Marianum Fruit Extract] or PhytoCellTec Malus Domestica [INCLUDES: Malus Domestica Fruit Cell Culture] marketed by Mibelle Biochemistry, Bioxilift [INCLUDES: Pimpinella Anisum Extract] or SMS Anti-Wrinkle [INCLUDES: Extract Seed ] marketed by Silab, Ca ²⁺ channel antagonists such as and not restricted to, alverine, manganese or magnesium salts, certain secondary or tertiary amines, retinol and its derivatives, resveratrol, idebenone, coenzyme Q10 derivatives, boswellic acid and its derivatives , GHK derivatives and / or salts, carnosine and its derivatives, DNA repairers such as and not restricted to, photoliase or endonuclease V T4 or chloride channel agonists, among their
Other enzymes.
In a particular embodiment, the wetting or moisture-retaining, humidifying or emollient substance is selected, for example, and not restricted to, from the group formed by polyols and polyethers such as glycerin, ethylhexylglycerine, caprylyl Glycol, pentylene glycol, butylene glycol , propylene glycol and its derivatives, triethylene glycol, polyethylene glycol, Glicereth-26, Sorbeth30; panthenol; pyroglutamic acid and its salts and derivatives; amino acids, such as serine, proline, alanine, glutamate or
25/49 arginine; ectoin and its derivatives; N- (2-hydroxyethyl) acetamide; W-lauryl-pyrrolidone carboxylic acid; W-lauryl-L-lysine; N-alpha-benzoyl-L-arginine; urea; creatine; a- and β- hydroxy acids such as lactic acid, glycolic acid, malic acid, citric acid or salicylic acid and its salts; polyglyceryl acrylate; sugars and polysaccharides, such as glucose, saccharide isomerate, sorbitol, pentaerythritol, inositol, xylitol, trehalose and their derivatives, sodium glucuronate, carrageenates (Chondrus crispus) or chitosan; glycosaminoglycans such as hyalauronic acid and its derivatives; aloe vera in any of its forms; honey; soluble collagen; lecithin and fofatidil choline; ceramides; cholesterol and its esters; tocopherol and its esters, such as tocopheryl acetate or tocopheryl linoleate; long-chain alcohols such as cetearyl alcohol, stearyl alcohol, cetyl alcohol, oleyl alcohol, isocetyl alcohol or octadecane-2-ol; long chain alcohol esters such as lauryl lactate, lactate miristila benzoate or C ₂ -C ₅ alkyl; fatty acids such as stearic acid, isostearic acid or palmitic acid; polyunsaturated fatty acids (PUFAs); sorbitans such as sorbitan distearate; glycerides such as glyceryl monoricinoleate, glyceryl monostearate, glyceryl stearate citrate or caprylic acid and capric acid triglyceride; sucrose esters such as sucrose palmitate or sucrose oletate; butylene glycol esters such as Dicaprilat and Dicaprat; fatty acids such as isopropyl isostearate, isobutyl palmitate, isocetyl stearate, isopropyl laurate, hexyl laurate, decyl oleate, cetyl palmitate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, isopropyl stearate, isopropyl stearate butyl, butyl myristate, isopropyl linoleate, 226/49 ethylhexyl palmitate, 2-ethylhexyl cocoate, decyl oleate, myristyl myristate; squalene; squalane; mink oil; lanolin and its derivatives; acetylated lanolin alcohols; silicone derivatives such as cyclomethicone, dimethicone or dimethylpolysiloxane; Antarcticine® [INCLUDES: Pseudoalteromonas yeast extract],
Xpertmoist
TH [INCLUDES:
Glycerin, Pseudoalteromone yeast extract, Xanthan gum, Proline, Alanine, Serine, Ethylhexylglycerin, Caprylyl Glycol] or Bodyfensine ™ [INCLUDES: Acetyl Dipeptide-3 Aminohexanoate] marketed by Lipotec, petrolatum; mineral oil; mineral and synthetic waxes; beeswax (wax alba); paraffin; or vegetable waxes and oils such as candelilla wax (Euphorbia cerifera), carnauba wax (Copemicia cerifera), shea butter (Butirospermum parkii), cocoa butter (Theobroma cacao), castor oil (Ricinus communis), oil sunflower (Helíanthus annuus), olive oil (Olea europaea), coconut oil (Cocos nucifera), babassu oil (Elaeis guineensis), wheat germ oil (Triticum vulgare), sweet almond oil (Prunus amygdalus dulces) , musk rose oil (Rosa moschata), wild soybean oil (Glycine Soy), grape seed oil (Vitis vinifera), marigold oil (Calendula officinalis), jojoba oil (Simmonsis chinensis), oil mango (Mangifera indica), avocado oil (Persea gratíssima), and / or mixtures thereof, among others.
Furthermore, in another particular modality, the healing stimulating agent, healing healing agent, reepithelializing stimulating agent and / or supporting reepithelializing agent is selected, for example, and not restricted to, the group formed by extracts of Aristoloquia clematis, Centella asiatica, Rosa moschata, Echinacea angustifolia, Symphytum officínale, Equisetum arvense, Hypericum perforatum, Mimosa tenuiflora, Persea
27/49 gratisima, Prunus africanam, Tormentilla erectea, Aloe vera, Polyplant® Epithelizing [INCLUDES: Calendula Officinalis, Hypericum Perforatum, Chamomilla Recutita, Rosmarinus Officinalis] marketed by Provital, Cytokinol® LS 9028 [INCLUDES: Hydrolyzed Casein, Hydrolyzed Casein , Lysine HC1] sold by Laboratories Serobiologiques / Cognis or Deliner® [INCLUDES: Popa de Zea May (Maize)] sold by Coletica / Engelhard / BASF, allantoin, cadherins, integrins, selectins, hyalauronic acid receptors, immunoglobulins, factors fibroblast growth factors, connective tissue growth factors, platelet-derived growth factors, vascular endothelial growth factors, epidermal growth factors, insulin-like growth factor, keratinocyte growth factors, colony stimulating factors, beta factor transformation growth factor, tumor necrosis alpha factor, interferons, interleukins, Me matrix taloproteinases, tyrosine protein receptor phosphatases, Antarcticine [INCLUDES: Decorinyl®
Yeast Extract from Pseudoalteromonas], [INCLUDES: Tripeptide-10 Citrulline], Trylagen® [INCLUDES: Yeast Extract from Pseudoalteromonas, Hydrolyzed Wheat Protein, Hydrolyzed Soy Protein, Tripeptide-10 Citrulline, Tnpeptide-1], Xpertmoist : Glycerin, Pseudoalteromone yeast extract, Xanthan gum, Proline, Alanine, Serine, Ethylhexylglycerin, Caprylil Glycol] or Bodyfensine ™ [INCLUDES: Acetyl Dipeptide-3 Aminohexanoate] marketed by Lipotec, among others.
In a particular embodiment, the stimulating agent for the synthesis of dermal or epidermal macromolecules is selected, for example, and not restricted to, from the group formed by collagen-stimulating agent, elastin-synthesizing agent, stimulating agent
28/49 as elastase stimulants stimulating agents stimulating agents
Saccharomyces cerevisiae, officinalís, Decorin synthesis vaccinium, laminin synthesis stimulating agent, chaperone synthesis stimulating agent, sirtuin synthesis stimulating agent, hyalauronic acid synthesis stimulating agent, aquaporin synthesis stimulating agent, fibronectin synthesis, collagen degradation inhibiting agents, serine protease inhibiting agents such as leukocyte or cathepsin G, fibroblast proliferation agents, adipocyte proliferation, adipocyte differentiation, glycosamine glycan synthesis stimulating agents and DNA repair agents and / or Protective DNA agents, such as and not restricted to, extracts of Centella asiatica,
Solanum tuberosum, Rosmarínus angustifolium, Macrocystis pyrifera seaweed extract, Padína pavonica, soy extract, malt, flax, sage, red cloves, kakkon, lupine plants, hazelnut extract, corn extract, yeast extract, beech branch extracts , legume seed extract, plant hormone extract such as gibberellins, auxins or cytokinins, among others, or saline zooplankton extract, the milk fermentation product with Lactobacillus Bulgaricus, asiaticosides and their derivatives, vitamin C and its derivatives, acid cinnamic and its derivatives, Matrixyl® [INCLUDES: Palmitoil Pentapeptide-3], Matrixyl® 3000 [INCLUDES: Palmitoil
Tetrapeptide-3, Palmitoyl Oligopeptide] or Biopeptide CL ™ [INCLUDES: Glycerol Polymethacrylate, Propylene Glycol, sold by Sederma / Croda, Yeast Extract
Pseudoalteromonas], Decorinyl® [INCLUDES: Tripeptide-10
Citrulline], Serilesine® [INCLUDES: Hexapeptide-10], Lipeptide [INCLUDES: Hydrolyzed vegetable protein], Aldenine® [INCLUDES:
Palmitoil Oligopeptide] Antarcticine® [INCLUDES:
29/49
Hydrolyzed Wheat Protein, Hydrolyzed Soy Protein, Tripeptide-1], Relistase ™ [INCLUDES: Acetilarginyltriptofil
Acetyl
Acetyl
Lipotec,
Beta-Sitosterol
Diphenylglycine], Thermostressine ™ [INCLUDES:
Tetrapeptide-22] or Peptide AC29 [INCLUDES Tripeptide-30 Citrulline] marketed by
Drieline® PF [INCLUDES: Yeast beta-glucan] sold by Alban Muller, Phytovityl C® [INCLUDES: Aqua, Zea Mays Extract] sold by Solabia, Collalift® [INCLUDES: Hydrolyzed Malt Extract] sold
Coletica / Engelhard / BASE, Phytocohesine PSP ™ [INCLUDES:
Sodium] marketed by
Sulfate by
Seporga / VIncluience / ISP, minerals such as calcium, among others, retinoids and their derivatives, isoflavonoids, carotenoids, in particular lycopene, pseudodipeptides, retinoids and their derivatives such as retinol or retinyl palmitate, among others or heparinoids, among others.
In a particular embodiment, the elastin degradation inhibiting agent is selected, for example, and not restricted to, from the group formed by Elhibin® [INCLUDES: Glycine Soy Protein (Soybean)], Preregen® [INCLUDES: Protein of Soy Glycine (soybean), Oxidorreductases] or Regu®Age [INCLUDES: Hydrolyzed Rice Bran Protein, Soy Glycine Protein (Soybean), Oxidorreductases] marketed by Pentapharm / DSM, Juvenesce [INCLUDES: Etoxidiglycol and Triglyceride and Triglyceride Caprylic, Retinol, Ursolic Acid, Phytomenadione, Ilomastat], Micromerol ™ [INCLUDES: Pyrus Malus Extract], Heather Extract [INCLUDES: Calluna Vulgaris Extract], Extracellium® [INCLUDES
Hydrolyzed] or Flavagrum ™ PEG [INCLUDES
Esperetina Laurato] commercialized
Coletica / Engelhard / BASF, Proteasyl® TP LS8657 [INCLUDES: Pisum Sativum Extract] sold by Laboratoires Sérobiologiques / Cognis, Relistase ™ [INCLUDES:
Potato Protein Isostearate PEG-6, for
30/49
Acetylarginyltryptophil Diphenylglycine] marketed by Lipotec, Sepilift DPHP [INCLUDES: Dipalmitoil Hydroxyproline] marketed by SEPPIC, Vitaderm® [INCLUDES: Alcohol, Water (Aqua), Glycerin, Hydrolyzed Rice Protein, Sodium Hydrate Hydrate, Isohydrate, Ursolate Extract, Urine Sodium Hydrate ] marketed by Rahn, Gatuline® Age Defense 2 [INCLUDES: Juglans Regia Seed Extract (Common Walnut)] marketed by Gattefosse, IP 2000 [INCLUDES: Dextran, Trifluoroacetyl Tripeptide-2] marketed by IEB and Atrium Innovations / Unipex Innovations , Radicaptol [INCLUDES: Propylene glycol, Water (Aqua), Passiflora Incarnata Flower Extract, Ribes Nigrum Leaf Extract (blackcurrant), Vitis Vinifera Leaf Extract (grape)] marketed by Solabia or ViaPure ™ Boswellia [INCLUDES: Olive extract (Boswellia Serrata)] sold by Soliance, among others.
In a particular embodiment, a matrix metalloproteinase inhibiting agent is selected, for example, and not restricted to, from the group formed by Ursolic Acid, isoflavones such as genistein, quercetin, carotenoids, lycopene, soy extract, blackberry extract, extract rosemary, Trifolium pratense extract (red clove), Phormium tenax extract (New Zealand flax), kakkonto extract, sage extract, retinol and its derivatives, retinoic acid and its derivatives, sapogenins such as diosgenin, hecogenin, smilagenin , sarsapogenin, tigogenin, iamogenin and iucagenin, among others, Collalift® [INCLUDES: Hydrolyzed Malt Extract], Youths [INCLUDES: Ethoxyglycol and Caprylic Triglyceride, Retinol, Ursolic Acid, Phytomenadione, Ilomastat] or EquiStat Extract Malus, Glycine Soybean Extract] marketed by Coletica / Engelhard / BASF, Pepha®-Timp [INCLUDES: Human Oligopeptide-20], Regu-Age
31/49 [INCLUDES: Hydrolyzed Rice Bran Protein,
Glycine Soy, Oxidorreductases] or Colhibin [INCLUDES: Hydrolyzed Rice Protein] marketed by Pentapharm / DSM, Lipeptide [INCLUDES: Hydrolyzed vegetable protein] or AC29 Peptide [INCLUDES: Acetyl Tripeptide-30 Citrulline] marketed by Lipotec, Litchiderm ™ Litchi Chinensis Pericarp Extract] or Arganyl ™ [INCLUDES: Argania Spinosa Leaf Extract] marketed by Laboratories Sérobiologiques / Cognis, MDI Complex®
Glycosaminoglycans] or ECM-Protect® [INCLUDES: Water Dextran, Tripeptide-2] marketed by Innovations / Unipex Innovations, Dakaline [INCLUDES:
Amygdalus Dulcis, Anogeissus Leiocarpus Bark Extract] marketed by Soliance, Homeostatin [INCLUDES: Enteromorpha Compressa, Caesalpinia Spinosa] marketed by Provital, Timp-Peptide [roposed INCLUDE: Acetyl
Hexapeptide] or Modulin ECM [roposed INCLUDE: Palmitoyl Tripeptide] sold by Infinitec Activos, IP2000 [INCLUDES: Dextran, Trifluoroacetyl sold by Institut Europeen
Cellulaire / Unipex, Actimp 1.9.3® [INCLUDES: Hydrolyzed Lupine Protein] marketed by Expanscience Laboratories, Vitaderm® [INCLUDES: Alcohol, Water (Aqua), Glycerin, Hydrolyzed Rice Protein, Ilex Aquifolium Extract, Sodium Ursolate, Sodium Oleanolate] adapalene, tetracyclines and [INCLUDES: (Aqua), Atrium
Prunus
Tripeptide-2] from Biologie commercialized its derivatives by Rahn, such as minocycline, rolithetracycline, chlortetracycline, metacycline, oxytetracycline, doxycycline, demeclocycline and its salts, Batimastat [BB94; [4- (N-hydroxyamino) -2R-isobutyl-3S (thiophene-2-yltimethyl) succinyl] -L-phenylalanine-N-methyl-amide], Marimastat [BB2516; [2S- [N-4 (R *), 2R *, 3S]] -N-4 [2,2-dimethyl1- [methylaminocarbonyl] propyl] -Wl, 2-dihydroxy-3- (2-methylpropyl) butanediamide] , among others.
32/49
In a particular modality, the firmament and / or redensification agent is selected, for example, and not restricted to, from the group formed by extracts of Malpighia punicitolia, Cynara scolymus, Gossypium herbaceum, Aloe Barbadensis, Panicum miliaceum, Morus nigra, Sesamum indicum, Glycine Soy, Triticum vulgare, Pronalen® Refirming HSC [INCLUDES: Triticum Vulgare, Silybum Marianum, Glycine Soy, Equisetum Arvense, Alchemilla Vulgaris, Medicago Sativa, Raphanus Sativus] or Polyplant® Refirming Fucus, Fenugreek sold by Provital, Lanablue® [INCLUDES: Sorbitol, Algae Extract] sold by Atrium Innovations / Unipex Innovations, Pepha®-Nutrix [INCLUDED: Natural Nutrition Factor] sold by Pentapharm / DSM, plant extracts containing isoflavones, Biopeptide EL
TM [INCLUDES:
Palmitoil
Palmitoil
Propylene
Matrixyl®
Oligopeptide], Biopeptide CL ™ [INCLUDES:
Oligopeptide], Vexel® [INCLUDES: Water (Aqua), Glycol, Lecithin, Caffeine, Palmitoil Carnitine], [INCLUDES: Palmitoil Pentapeptide-3], Matrixyl® 3000 [INCLUDES: Palmitoil Tetrapeptide-3, Palmitoil Oligopeptide] or Bio-Bustyl ™ [INCLUDES: Glycerol Polymethacrylate, Rahnella Soy Protein Yeast, Water (Aqua), Propylene PEG-8, Palmitoil Oligopeptide] Sederma / Croda, Dermosaccharides® HC Water (Aqua), Glycosaminoglycans, [INCLUDES: Mannitol, Cyclodextrin, glycol, Glycerin, marketed by [INCLUDES: Glycerin,
Glycogen], Aglycal
Glycogen, Aratostaphylos Uva Ursi Leaf Extract], Cytokinol® LS [INCLUDES: Hydrolyzed Casein, Hydrolyzed Yeast Protein, Lysine HC1] or Firmiderm® LS9120 [INCLUDES: Terminalia Catappa Leaf Extract, Black Sambucus Flower Extract, PVP , Tannic Acid] marketed by
Laboratoires Serobiologiques / Cognis, Liftline®
INCLUDES:
Hydrolyzed Wheat Protein], Raffermine® [INCLUDES: Flour
33/49 Hydrolyzed Soy] or Rídulisse C® [Hydrolyzed Soy Protein] sold by Silab, Serilesine® [INCLUDES: Hexapeptide-10], Decorinyl ™ [INCLUDES: Tripeptide-10 Citrulline] or Trylagen® [INCLUDES: Yeast extract Pseudoalteromone, Hydrolyzed Wheat Protein, Hydrolyzed Soy Protein, Tripeptide-10 Citrulline, Tripeptide-1] marketed by Lipotec, Ursolisome® [INCLUDES: Lecithin, Ursolic Acid, Atelocolagen, Xanthan Gum, Chondroitin Sodium] INCLUDES: Hydrolyzed Malt Extract] marketed by Coletica / Engelhard / BASF, Syn®-Coll [INCLUDES: Palmitoyl Tripeptide-5] marketed by Pentapharm / DSM, Hydriame® [INCLUDES: Water (Aqua), Glycosaminoglycans, Sclerotum Gum] by Atrium Innovations / Unípex Innovations or IP2000 [INCLUDES: Dextran, Trifluoroacetyl Tripeptide-2] sold by Institut Europeen de Biologie Celluiaire / Unipex, among others.
In a particular embodiment, the peeling agent and / or keratolytic agent and / or exfoliating agent is selected, for example, and not restricted to, from the group formed by hydroxy acids and their derivatives, β-hydroxy acids, in particular salicylic acid and its derivatives , or gentisic acid; α-hydroxy acids and their salts, such as glycolic acid, ammonium glycolate, lactic acid, 2-hydroxyoctanoic acid, α-hydroxycaprylic acid, mandelic acid, citric acid, malic acid or tartaric acid; a- and β-hydroxybutyric acids; polyhydroxy acids such as gluconic acid, glucuronic acid or saccharic acid; keto acids such as pyruvic acid, glyoxylic acid; pyrrolidine carboxylic acid; cystic acid and derivatives; aldobionic acids; azelaic acids and their derivatives such as azeloyl diglycinate; ascorbic acid and its derivatives such as 6O-palmitoylascorbic acid, ascorbyl glycoside, acid
34/4 9 ascorbic dipalmitoyl, magnesium-2-phosphate ascorbic acid salt (MAP), sodium-2-phosphate ascorbyl acid salt (NAP), ascorbyl tetraisopalmitate (VCIP); nicotinic acid, its esters and nicotinamide (also known as vitamin B3 or vitamin PP); nordihidroguaiarético acid; urea; oligofucoses; cinnamic acid; derivatives of jasmonic acid; hydroxystiibenes such as resveratrol; Saccarum officinarum extract; enzymes involved in the desquamation or degradation of corneodesmosomes, such as glycosidases, corneal extract chemotropic enzyme (SCCE) or other proteases such as trypsin, chymotrypsin, sutilain, papain or bromelain; chelating agents such as ethylenediaminetetraacetic acid (EDTA) and its salts, amino sulfide compositions such as 4 (2-hydroxyethyl) piperazine-1-ethanesulfonic acid (HEPES) or methylglycine Sodium Diacetate (TRILON® M marketed by BASF); 2oxothiazolidine-4-carboxylic acid derivatives (procystein); sugar derivatives such as O-octanoyl-6-D-maltose and Nacetylglycosamine; chestnut extract (Castanea sativa) such as that marketed by SILAB under the name Recoverine® [INCLUDES: Water (Aqua), Castanea Sativa Seed Extract]; prickly pear extract (Opuntia ficus-indica) such as that marketed by SILAB such as Exfolactive® [INCLUDES: Hydrolyzed Opuntia Ficus Indica Flower Extract]; or Fitosfingosina SLC® [INCLUDES: Saliciloil Fitosfingosina] marketed by Degussa / Evonik, Peel-Moist [INCLUDES: Glycerin, Papain, Calcium Pantothenate, Xanthan Gum, Caprylyl Glycol, Urea, Magnesium Lactate, Ethylhexylglycerine, Lactate, Lactate, Lactate, Potato Alanine, Proline, Magnesium Chloride, Sodium Citrate] sold by Lipotec; extract or combination of extracts from Saphora japonica, papaya, pineapple, pumpkin or sweet potato and / or mixtures thereof.
35/49
applications
A third aspect of this invention relates to the use of the exopolysaccharide of the invention in the preparation of a cosmetic or dermopharmaceutical composition for the treatment and / or care of the skin, mucous membranes, hair and / or nails.
In a particular embodiment, this invention relates to the use of the exopolysaccharide in the preparation of a cosmetic or dermopharmaceutical composition for the treatment and / or prevention of aging. Preferably, the treatment and / or prevention of aging is a treatment and / or prevention of wrinkles on the skin and / or dry skin.
In another particular embodiment, this invention relates to the use of exopolysaccharide in the preparation of a cosmetic or dermopharmaceutical composition for the treatment and / or care of any conditions, disorders and / or diseases that are a result of a lack or decrease in hydration. skin, mucous membranes, hair and / or nails. Preferably, affections, disorders and / or diseases are selected from the group formed by dry skin, xerosis, hyperkeratosis, hyperkeratosis response, palmar and plantar hyperkeratosis, calluses and calluses, actinic keratosis, non-actinic keratosis, atopic dermatitis, eczema of contact, seborrheic dermatitis, dandruff, neonatal seborrheic dermatitis in babies, acne, rosacea, wart, parakeratosis, pityriasis, palmoplantar lichen, chapped lips, vaginal dryness, dry eye, dry hair, brittle hair and nails.
Examples of cosmetic or dermopharmaceutical compositions for the treatment and / or care of skin, mucous membranes, hair and / or nails include creams, multiple emulsions, such as and not restricted to, oil and / or silicone in water emulsions, water emulsions in oil and / or ichthyosis, psoriasis, flat, silicone keratoderma, water / oil / water emulsions or
6/49 water / silicone / water and oil / water / oil or silicone / water / silicone emulsions, anhydrous compositions, aqueous dispersions, oils, milks, balms, foams, lotions, gels, cream gels, hydroalcoholic solutions, solutions hydroglycolic, hydrogels, ointments, serum, soaps, shampoos, conditioners, serum, polysaccharide films, ointments, mousses, perfume ointments, powders, bars, pencils and sprays or aerosols (sprays), including formulas let dry or rinse, bandages, gauze, t-shirts, socks, pants, underwear, belts, gloves, diapers, sanitary napkins, adornments, covers, flannels, adhesive bandages, non-adhesive bandages, occlusive bandages, microelectric bandages and / or facial masks, makeup products such as creams makeup base, such as fluid foundation creams and compact foundation creams, makeup removal lotions, makeup removal milks, eye concealers, eye shadows, lipsticks, lip balms , lip gloss and powders among others. Cosmetic or dermopharmaceutical compositions containing the exopolysaccharide of this invention can also be incorporated into products for the treatment, care and / or cleaning of nails and cuticles such as nail polish, nail polish removers and lotions to remove cuticles, among others. The compositions containing the exopolysaccharide of this invention can be applied to the skin, mucous membranes, hair and / or nails or can be administered orally or parenterally depending on the requirements for treatment and / or care for a condition, disorder and / or disease.
The cosmetic or dermopharmaceutical compositions of this invention can be applied to the skin by mechanisms of iontophoresis, sonophoresis, electropermeabilization, microelectric bandages, mechanical pressure, osmotic pressure gradient, occlusive cure, microinjections or injections without
37/49 needles by pressure mechanisms, such as oxygen pressure injections or any combination thereof, to obtain greater penetration of the exopolysaccharide of the invention.
A further aspect of this invention relates to a method of treatment and / or care of the skin, mucous membranes, hair and / or nails which comprises the administration of an effective amount in a cosmetic and / or dermopharmaceutical form of the exopolysaccharide, preferably in the form of a cosmetic or dermopharmaceutical composition that contains the same.
Another additional aspect of this invention relates to a method for the treatment and / or care of any affections, disorders and / or diseases of mammals, preferably humans, which are a consequence of a lack or decrease in hydration of the skin, mucous membranes , hair and / or nails, which comprises the administration of an effective amount of the exopolysaccharide, preferably in the form of a cosmetic or dermopharmaceutical composition that contains them.
In a preferred embodiment, the conditions, disorders and / or diseases that are a consequence of a lack or decrease in skin hydration, mucous membranes, hair and / or nails are selected from the group formed by dry skin, xerosis, hyperkeratosis, hyperkeratosis response , palmar and plantar hyperkeratosis, calluses and calluses, actinic keratosis, non-actinic keratosis, atopic dermatitis, contact eczema, seborrheic dermatitis, dandruff, neonatal seborrheic dermatitis in babies, acne, rosacea, wart, ichthyosis, psoriasis, parakeratosis lichen, pityriasis flat, palmoplantar keratoderma, chapped lips, vaginal dryness, dry eye, dry hair, brittle hair and nails.
In a further aspect, this invention relates to the treatment and / or care that reduces, delays and / or
38/49 avoids the signs of aging and that includes the administration of an effective amount of the exopolysaccharide, preferably in the form of a cosmetic or dermopharmaceutical composition that contains it. Preferably, the treatment and / or care that reduces, delays and / or prevents the signs of aging is a treatment and / or prevention of skin wrinkles and / or skin dryness.
In a more particular aspect, the treatment and / or care of this invention is performed by topical or transdermal application, preferably, topical or transdermal application is performed by mechanisms of iontophoresis, sonophoresis, electropermeahilization, mechanical pressure, osmotic pressure gradient, occlusive cure , microinjections, with injections without needles by pressure mechanisms, microelectric bandages or any combination thereof.
In another aspect in particular, treatment and / or care is carried out by oral administration.
In another aspect in particular, treatment and / or care is carried out by parenteral application.
The frequency of application or administration can vary widely, depending on the needs of each patient and the severity of the condition, disorder or disease to be treated or cared for, suggesting a range of application or administration from once a month to ten times a day , preferably once a week to four times a day, more preferably three times a week to three times a day, even more preferably once or twice a day.
This invention is understood more clearly with the help of the following examples, without limitation and included only for illustrative purposes that describe the preparation and characterization of exopolysaccharides and compositions containing them according to the invention.
39/49
DESCRIPTION OF THE FIGURES
Figure 1 shows a comparative study of water retention between the exopolysaccharide of this invention and hyalauronic acid using the dynamic vapor absorption technique.
EXAMPLES
Example 1: Preparation and isolation of the exopolysaccharide secreted by the strain CNCM 1-4150 that corresponds to the species Pseudoalteromonas sp.
a) CNCM 1-4150 strain cultivation method that corresponds to the species Pseudoalteromonas.
The CNCM 1-4150 strain was grown in a fermenter at 29 ° C and pH 7.5, whose broth contained the medium 2216E (ZoBell CEJ Mar. Res., 1941, 4:42.) Enriched with glucose ( 20 g / 1). An inoculum was prepared with 10% (v / v) of a previous culture and the fermentation duration was extended to 72 hours. The speed of aeration and agitation was 2 vvm and 250 rpm, respectively.
b) Purification of the exopolysaccharide.
The bacterium was separated from the broth by centrifugation at 12,000 g for 45 minutes. The polysaccharide was purified with distilled water by ultrafiltration with a polyethersulfan membrane for polysaccharides of more than 100 KDa in molecular weight. Once purified, the polysaccharide was depolymerized by radical depolymerization (Volpi N. et al. Anal. Biochem., 1992, 200: 100 to 107), which resulted in a polymer with a molecular weight between 3,000 and 40,000 Da.
Example 2: Physico-chemical characterization of the exopolysaccharide produced by the bacterial strain CNCMI-4150 that corresponds to the species Pseudoalteromonas sp.
a) Chemical analysis
The content of neutral and acid monosaccharides of the obtained exopolysaccharide was determined according to that described in example 1 by hydrolysis and gas chromatography
40/49 according to the method described by Kamerling et al. Bíochem. J., 1975 151: 491 to 495 and modified by Montreuil et al. in 1986, glycoproteins. No Carbohydrate analysis: a practical approach. Eds Chaplin et Kennedy, IRL Press, Oxford, Washington DC, pages 143 to 204. The percentage relationship of sugars obtained was 7.25% mannose, 24.64% glucose, 23.19% glucuronic acid, 11, 59% galacturonic acid, 24.64% galactose and 8.70% Nacetylglycosamine.
Example 3: Preparation of a cosmetic composition of the exopolysaccharide excreted by the bacterial strain CNCM I4150.
In a suitable container, the following ingredients were added in this order: water [INCLUDES: Water (Aqua)], Phenonip [INCLUDES: Phenoxy ethanol, Methylparaben, Ethylparaben, Butylparaben, Propylparaben, Isobutylparaben], Abiol [INCLUDES: Imidazolidinyl Urea] and Propylene glycol USP / EP [INCLUDES: Propylene glycol] (ingredients from phase A). The mixture of ingredients in phase A was subjected to constant stirring and subsequently, Carbopol ETD 2020 [INCLUDES: C10-30 Alkyl Acrylate Acrylates / Crospolymer] was added (phase B). The resulting mixture was heated in a microwave to 65 ° C.
In another container, Lipomulse 165 [INCLUDES: Glyceryl stearate, PEG-100 stearate], CO-1695 alcohol [INCLUDES: Cetyl alcohol], Edenor L2SM [INCLUDES: Stearic acid, Palmitic acid], Caprylic acid triglycerides [INCLUDES: Caprylic triglycerides / Cápricos] and Massocare HD [INCLUDES: Isohexadecane] were added (ingredients from phase C). Phase C was dissolved in a bath at approximately 75 ° C.
In a third container, the exopolysaccharide obtained according to example 1 in water with salicylate of
41/49 sodium [INCLUDES: sodium salicylate] was dissolved (phase D).
Then, the mixture of ingredients from phase C was added to the mixture of ingredients from A and B, under turbine stirring at 75 ° C until the emulsion was formed.
Subsequently, when the previous mixture of A, B and C was cooled to 40 ° C, the dissolution of the exopolysaccharide was added (phase D). Finally, the pH was adjusted to 6 by the addition of Triethanolamine 99 [INCLUDES: Triethanolamine] dropwise (phase Ε), which obtained a cosmetic composition with the proportions shown in table 1.
THE INGREDIENTWater % by weight 77.05 THE Phenonip 0.80 THE Abiol 0.30 THE Propylene glycol 2.00 Ç Lipomulse 165 6.00 Ç CO-1695 alcohol 0.70 Ç Edenor L2SM 1.80 Ç Triglycerides 8.00 ç Capriclics Massocare HD 3.00 B Carbopol ETD 2020 0.25 D Exopolysaccharide from 0.01 D CNCM strain 1-4150 Sodium salicylate 0.005 D Water 0.085 AND Triethanolamine 99 q. s.
Table 1
Example 4: Preparation of a cosmetic composition of the exopolysaccharide excreted by the bacterial strain CNCM I4150.
The cosmetic composition of this example was prepared following the instructions for preparing the composition of example 3 with the same ingredients, but using the amounts in table 2.
INGREDIENT% by weight
Water
76, 10
42/49
THE Phenonip 0.80 THE Abiol 0.30 THE Propylene glycol 2.00 Ç Lipomulse 165 6.00 Ç CO-1695 alcohol 0.70 Ç Edenor L2SM 1.80 Ç TriglyceridesCapricorns 8.00 Ç Massocare HD 3.00 B Carbopol ETD 2020 0.30 D Exopolysaccharide fromCNCM strain 1-4150 0.10 D Sodium salicylate 0.05 D Water 0.85 AND Triethanolamine 99 q. s .
Table 2
Example 5: Comparative study of water retention between hyalauronic acid and exopolysaccharide from strain CNCM 1-4150.
This example studies changes in weight over time at any relative humidity level between 0 and 95% for a sample of the exopolysaccharide from the bacterial strain CNCM 1-4150 compared to hyalauronic acid.
The experiments were carried out with the technique of 10 dynamic vapor sorption (DVS), with a thermogravimetric analyzer TA Instruments Q5000 SA (TGA), treating the values obtained with Universal Analysis 2000 version 4.5A (TA Instruments). The protocol used considers an initial equilibrium step at 60 ° C, establishing a humidity of 0.0% and a subsequent balance at 33 ° C, after which the relative humidity begins to be increased in stages of 10%. Once 95% has been achieved, successive stages of decreasing relative humidity are performed. Throughout the
43/49 entire period of variation in relative humidity the weight of the exopolysaccharide is recorded. After that, the same experiment was performed under the same conditions with hyalauronic acid.
The results of the studies carried out showed that the exopolysaccharide of the invention shows a better water retention profile than hyalauronic acid (Figure 1}. When calculating the water retention at the point of maximum relative humidity (95%), the value obtained by the exopolysaccharide it was 12.7% higher than that obtained with hyalauronic acid.
Example 6: In vivo study of skin hydration.
A comparative in vivo study of the skin's moisturizing ability of the cosmetic composition in example 4 and its placebo composition, which contained the same ingredients and in the same percentages as the composition of example 4, except for the exopolysaccharide of the CNCM 1-4150 strain which was replaced by water.
The measurements of this study were performed in a bioclimatic room (24 ± 2 ° C; 50 + 10% relative humidity) in order to keep the temperature and humidity constant during the measurement. Measurements of skin hydration were performed on the cheeks using a Corneometer CM 825 (Courage & Khazaka). Twenty women with an average age of 44.3 years participated in the study; they were instructed not to apply any cosmetic or dermopharmaceutical composition other than those used in the study during its duration or during the 24 hours before the study started.
All volunteers applied a fixed amount of 0.4 ml of the placebo composition on the right side of their faces and 0.4 ml of the cosmetic composition of example 4 on the left side of their faces twice a day for 20 days, always applying the composition placebo on the right side and the composition of example 4 on the left side of their faces. The volunteers did not apply any cosmetic composition to their faces because
44/49 at least 12 hours before undergoing instrumental measurements.
The skin hydration measurements were performed 2 and 8 hours after the first application of the previous compositions, as well as 20 days after the beginning of the study.
Table 3 shows the average percentages of improvement in skin hydration of the placebo composition and the cosmetic composition of example 4 that contains the exopolysaccharide from the CNCM 1-4150 strain.
T2 hoursTo Tg hours To T20 days - To Composition 12.1% 7.1% 0% placebo Composition of 36.8% 30.8% 37.2% example 4
Table 3
The results in the table clearly show that the composition of example 4 has greater skin hydrating power than the placebo composition and, therefore, it is shown that the exopolysaccharide described in this invention improves skin hydration.
Example 7: In vivo study of the reduction of skin roughness.
A comparative in vivo study of the ability to reduce skin roughness, ie, anti-wrinkle effect, the cosmetic composition of example 3 and its placebo composition that contained the same ingredients and in the same percentages as the composition of example 3 except for the exopolysaccharide of strain CNCM 1-4150 that has been replaced by water.
The measurements for this study were performed in a bioclimatic room (24 ± 2 ° C; 50 + 10% relative humidity) to maintain a constant temperature and humidity during the
45/49 measurements. The measurements of skin roughness were performed using replicas of silicone skin using adhesive discs (3M, 24x40) and a fast-setting synthetic polymer (SILFLO, Flexico Ltd). The silicone replicas of the skin were analyzed using image processing software (Quantilines, Monaderm) that enabled a maximum roughness value to be determined (depth of the wrinkle, referred to in the study as Rz). Anti-wrinkle efficiency is shown by a decrease in the Rz value. Twenty women with an average age of 41 participated in the study; they were instructed not to apply any cosmetic or dermopharmaceutical composition other than that used in the study during its duration or during the 24 hours before the study started.
All volunteers applied a fixed amount of 0.4 ml of the placebo composition on the right side of their faces and 0.4 ml of the cosmetic composition of example 3 on the left side of their faces twice a day for 20 days, always applying the composition placebo on the right side and the composition of example 4 on the left side of their faces. The volunteers did not apply any cosmetic composition to their faces for at least 12 hours before going through instrumental measurements.
The skin replicas were performed 2 and 8 hours after the first application of the previous compositions, as well as 20 days after the beginning of the study.
Table 4 shows the average percentages of percentage reduction of the maximum roughness (Rz) of the skin of the placebo composition and of the cosmetic composition of example 3 that contains the exopolysaccharide of the strain CNCM 1-4150.
T ₂ hours ^- Tq hours ^- To ^ 20 days ^- To
46/49
Composition -0.1% placebo
Composition of -11.1% example 3
5.6%
-8.4%
3.9%
-9.3%
Table 4
The results in Table 4 clearly show that the composition of Example 3 has a decreasing effect on the maximum roughness Rz and, therefore, it has been shown that the exopolysaccharide described in this invention has an anti-wrinkle effect.
Example 8: Preparation of a cosmetic composition of the exopolysaccharide excreted by the bacterial strain CNCM I4150 and Antarcticine®.
The cosmetic composition of this example was prepared following the instructions for preparing the composition of example 3 with the ingredients and quantities in table 5. In the preparation of phase D, Antarcticine® [INCLUDES: Pseudoalteromonas yeast extract] was also added with salicylate sodium [INCLUDES: sodium salicylate].
INGREDIENT % by weight THE Water 75, 59 THE Phenonip 0.80 THE Abiol 0.30 THE Propylene glycol 2.00 Ç Lipomulse 165 6.00 Ç CO-1695 alcohol 0.70 Ç Edenor L2SM 1.80 Ç Caprylic Triglycerides, Capric 8.00 Ç Massocare HD 3.00 B Carbopol ETD 2020 0.30 D Exopolysaccharide of the CNCM 1-4150 strain 0.10 D Antarcticine® 0.10 D Sodium salicylate 0, 06 D Water 1.25 AND Triethanolamine 99 q. s.
Table 5
47/49
Example 9: Preparation of a cosmetic composition of the exopolysaccharide excreted by the bacterial strain CNCM I4150 and Serilesine®.
The cosmetic composition of this example was prepared following the instructions for preparing the composition of example 3 with the ingredients and amounts from table 6. In the preparation of phase D, Serilesine® [INCLUDES: Hexapeptide-10] was also added.
INGREDIENT % by weight THE Water 76.00 THE Phenonip 0.80 THE Abiol 0.30 THE Propylene glycol 2.00 Ç Lipomulse 165 6.00 ' Ç CO-1695 alcohol 0.70 Ç Edenor L2SM 1.80 Ç Caprylic Triglycerides, Capric 8.00 Ç Massocare HD 3.00 B Carbopol ETD 2020 0.30 D Exopolysaccharide of the CNCM 1-4150 strain 0.10 D Serilesine® 0.10 D Sodium salicylate 0.05 D Water 0.85 AND Triethanolamine q. s .
Table 6
Example 10: Obtain liposomes containing the exopolysaccharide excreted by the bacterial strain CNCM 1-4150 bound to cationic poliquaternium-16 polymers
In a suitable container, the exopolysaccharide obtained according to example 1 in water [INCLUDES: Water (Aqua)] was added with sodium salicylate [INCLUDES: Sodium salicylate] and phase A was obtained. Water, Zemea ™ Propanediol [INCLUDES: Propanediol] and phenoxy ethanol were added to this phase (phases B to D). When all of the previous components dissolved, Leciflor 100 IP [INCLUDES: Lecithin] was added (phase E) little by little under intense
48/49 stirring until complete dissolution. After that, Labrasol [INCLUDES: Caprylic Glycerides / PEG-8 Caprics] was added (phase F) and left to stir for 10 to 15 minutes for an emulsion to be formed.
INGREDIENT % by weight THE Water 6 THE Sodium salicylate 0.03 THE Exopolysaccharide from the CNCM 1-4150 strain 1.5 B Water q.s.p. 100 Ç Zemea ™ Propanediol 8.50 D Phenoxy ethanol 1.70 AND Leciflor 100 IP 10.00 F Labrasol 4.00
Table 7
The sample was passed through a microfluidizer for one cycle at an inlet pressure of 8 MPa (80 bar) and 86 MPa (12,500 psi) at the outlet. The obtained liposomes were added to Luviquat® HM 552 [INCLUDES: Poliquaternium-16] in a 1.5: 1 liposome: polymer ratio under light agitation.
Example 11: Preparation of lipid nanoparticles coacervation capsules containing the microemulsion of the exopolysaccharide excreted by the bacterial strain CNCM 1-4150
Docusato de sodium USP [INCLUDES: Diethylhexil Sodium Sulfosuccinate] and Prisorine 3505 [INCLUDES: isostearic acid] were mixed in a suitable container (phase A). In another container, the exopolysaccharide obtained according to example 1 was dissolved in ethanol partially denatured with phthalate-Bitrex [INCLUDES: Denatured Alcohol]. Once dissolved, water was added (phase B).
Phase B was slowly added to phase A with stirring. In a container, the mixture of phases A and B was added to the ingredients of phase C, IP Ph. Eur refined soybean oil [INCLUDES: Soy Glycine Oil (Soya bean)], Arlacel 83V [INCLUDES: Sesquioleate of Sorbitan], and
49/49
Massocare HD [INCLUDES: Isohexadecane] (phase C) and a microemulsion was obtained.
In another suitable container, the following ingredients were added in this order: water, Amigei® [INCLUDES: Sclerotium gum], Argireline® [INCLUDES: Acetyl Hexapeptide-8], Zemea ™ Propanediol [INCLUDES: Propanediol] and phenoxy ethanol [INCLUDES: Phenoxy ethanol] (phase D), and was stirred until completely homogenized.
Then, the mixture of ingredients D was added to phases A, B and C, under turbine agitation until an emulsion was formed.
Finally, the mixture was homogenized under pressure in a microfluidizer for 3 cycles with a pressure of
input 8 MPa (80 bar) and pressure at out of 103 MPa (15,000 psi). Throughout the entire process the sample was maintained regulated by a thermostat at 25 ° C for the use of one circuit water / glycol cooling system. INGREDIENT % by weight Sodium docusate USP 1.08 THE Prisorine 3505 6, 10 B Exopolysaccharide of the strain 0.02 CNCM 1-4150 B Ethanol partially 0.24 denatured with phthalate-Bitrex B Water 0.56 Ç Refined soybean oil 12.00 IP Ph. Eur. Ç Arlacel 83V 4.30 Ç Massocare HD 5, 50 D Water q.s.p. 100 D Amigei® 0.50 D Argireline® 0.01 D Zemea ™ Propanediol 5.00 D Phenoxy ethanol 2.6
Table 8
1/6

权利要求:
Claims (6)
[1]
1. USE OF EXOPOLISACARIDE, characterized by being isolated from the strain of Pseudoalteromonas sp. with CNCM I-4150 deposit number when preparing a composition
5 cosmetic or dermopharmaceuticals for the treatment and / or care of skin, mucous membranes, hair and / or nails, in which said exopolysaccharide has a molecular weight between 100 and 800,000 Da and comprises at least four different neutral monosaccharides selected from mannose, glucose , galactose and N10 acetylglycosamine and two different acid monosaccharides selected from glucuronic acid and galacturonic acid.
[2]
2. USE OF EXOPOLISACARIDE, according to claim 1, characterized by this treatment and / or
15 care must be a treatment and / or prevention of aging of the skin, mucous membranes, hair and / or nails.
[3]
3. USE OF EXOPOLISACARIDE, according to claim 2, characterized by the treatment and / or prevention of skin aging being a treatment and / or prevention of
20 wrinkles on the skin.
[4]
4. USE OF EXOPOLISACARIDE, according to claim 1, characterized in that this treatment and / or care is the treatment and / or care of disorders, disorders and / or diseases that are a consequence of a lack or
25 decrease in hydration of the skin, mucous membranes, hair and / or nails.
[5]
5. USE OF EXOPOLISACARIDE, according to claim 4, characterized by the affections, disorders and / or diseases being selected from the group formed by
30 dry skin, xerosis, hyperkeratosis, reactive hyperkeratosis, palmar and plantar hyperkeratosis, calluses and calluses, actinic keratosis, non-actinic keratosis, atopic dermatitis, contact eczema, seborrheic dermatitis, dandruff, dermatitis
Petition 870180014816, of 23/02/2018, p. 7/15
2/6 neonatal seborrheic in babies, acne, rosacea, wart, ichthyosis, psoriasis, parakeratosis, pityriasis, lichen planus, palmoplantar keratoderma, chapped lips, vaginal dryness, dry eye, dry hair, brittle hair and nails.
6. USE OF EXOPOLISACARIDE, according to any one of the preceding claims, characterized in that the treatment and / or care of the skin is performed by topical, transdermal, oral or parenteral application of the exopolysaccharide.
7. USE OF EXOPOLISACARIDE, according to any one of the preceding claims, characterized in that the exopolysaccharide contains a chemical modification.
8. USE OF EXOPOLISACARIDE, according to any of the preceding claims, characterized by
The cosmetic or dermopharmaceutical composition comprises an effective cosmetic or dermopharmaceutical amount of the exopolysaccharide, and at least one excipient, adjuvant and / or ingredient acceptable in a cosmetic or dermopharmaceutical manner.
9. USE OF EXOPOLISACARIDE, according to any one of the preceding claims, characterized in that the exopolysaccharide is incorporated into an acceptable delivery system in a cosmetic or dermopharmaceutical manner or an extended release system.
10. USE OF EXOPOLISACARIDE, according to any of the preceding claims, characterized by the cosmetic or dermopharmaceutical composition, being absorbed in a solid organic polymer or solid mineral support selected from the group formed by talc, bentonite, silica,
30 starch and maltodextrin.
11. USE OF EXOPOLISACARIDE, according to any one of the preceding claims, characterized by the cosmetic or dermopharmaceutical composition being
Petition 870180014816, of 23/02/2018, p. 8/15
3/6 embedded in a fabric, non-woven fabric or medical device.
12. USE OF EXOPOLISACARIDE, according to any of the preceding claims, characterized
5 because the cosmetic or dermopharmaceutical composition is present in a formula selected from the group formed by multiple emulsions, oil and / or silicone in water emulsions, water in oil and / or silicone emulsions, water / oil / water or water emulsions / silicone / water and oil / water / oil type emulsions or
10 silicone / water / silicone, microemulsions, emulsions and / or solutions, liquid crystals, anhydrous compositions, aqueous dispersions, oils, milks, balms, foams, aqueous or oily lotions, aqueous and oily gels, creams, hydroalcoholic solutions, hydroglycolic solutions, hydrogels,
15 ointments, serums, soaps, shampoos, conditioners, facial masks, hair sprays, moisturizing serums, polysaccharide films, ointments, mousses, perfume ointments, pastes, powders, bars, pencils, sprays or aerosols or to be present in a formula for oral administration that
20 is selected from a group consisting of capsules, gelatin capsules, soft capsules, hard capsules, tablets, powders, granules, chewing gum, solutions, suspensions, emulsions, syrups, polysaccharide films, jellies or gelatines.
13. USE OF EXOPOLISACARIDE, according to claim 8, characterized in that excipients acceptable in a cosmetic or dermopharmaceutical manner, adjuvant and / or ingredient are selected from the group formed by inhibitors of the receptor group of
30 acetylcholine, muscle contraction inhibiting agents, anticholinergic agents, elastase inhibiting agents, matrix metalloproteinase inhibiting agents, melanin synthesis inhibiting or stimulating agents, agents
Petition 870180014816, of 23/02/2018, p. 9/15
4/6 bleaching or depigmentation agents, pro-pigmentation agents, artificial tanning agents, anti-aging agents, NO synthase inhibiting agents, 5α reductase inhibiting agents, lysyl inhibiting agents and / or
5 prolyl hydroxylase, antioxidants, free radical scavengers and / or atmospheric pollution agents, reactive carbonyl species scavengers, anti-glycation agents, antihistamines, antiviral agents, antiparasitic agents, emulsifiers, emollients, solvents
10 organic, liquid propellants, skin conditioners, humectants, moisture-retaining substances, alpha hydroxy acids, beta hydroxy acids, moisturizing creams, epidermal hydrolytic enzymes, vitamins, amino acids, proteins, pigments or dyes, paints, coagulating polymers,
15 thickeners, surfactants, softening agents, anti-wrinkle / anti-aging agents, agents capable of reducing or treating bags under the eyes, exfoliating agents, desquamating agents, keratolytic agents, microbicidal agents, fungicidal agents, fungistatic agents, agents
20 bactericides, bacteriostatic agents, stimulating agents for the synthesis of macromolecules and / or capable of inhibiting or preventing their degradation, stimulating agents for collagen synthesis, stimulating agents for elastin synthesis, stimulating agents for decorin synthesis, stimulating agents for
25 laminin synthesis, defensin synthesis stimulating agents, aquaporin synthesis stimulating agents, hyalauronic acid synthesis stimulating agents, fibronectin synthesis stimulating agents, sirtuin synthesis stimulating agents,
30 chaperone synthesis, agents that stimulate the synthesis of lipids and components of the horny extract, ceramides, fatty acids, agents that inhibit collagen degradation, agents that inhibit elastin degradation, agents that inhibit
Petition 870180014816, of 23/02/2018, p. 10/15
5/6 serine proteases, agents that stimulate the proliferation of fibroblasts, agents that stimulate the proliferation of keratinocytes, agents that stimulate the proliferation of adipocytes, agents that stimulate the proliferation of
5 melanocytes, keratinocyte differentiation stimulating agents, adipocyte differentiation stimulating agents, acetylcholinesterase inhibiting agents, skin relaxing agents, glycosaminoglycan synthesis stimulating agents, antihyperkeratosis agents, agents
10 comedolytic agents, antipsoriasis agents, DNA repair agents, DNA protective agents, stabilizers, anti-itch agents, agents for the treatment and / or care of sensitive skin, stabilizing agents, redensifying agents, restructuring agents, anti-stretch marks agents,
15 binding, sebum production regulating agents, lipolytic agents or lipolysis stimulating agents, anti-cellulite agents, antiperspirant agents, healing stimulating agents, supporting healing agents, re-epithelializing agents, supporting agents
20 reepithelialization, cytokine growth factors, soothing agents, anti-inflammatory and / or analgesic agents, anesthetic agents, agents acting on capillary circulation and / or microcirculation, angiogenesis stimulating agents, agents that inhibit vascular permeability,
25 venotonic agents, agents that act on cellular metabolism, agents to improve the dermis-epidermis junction, hair growth inducing agents, hair growth retarding or inhibiting agents, agents that slow hair loss, preservatives, perfumes, chelating agents,
30 plant extracts, essential oils, marine extracts, agents obtained from a biofermentation process, mineral salts, cell extracts and sunscreens, organic photoprotective agents or minerals active against
Petition 870180014816, of 23/02/2018, p. 11/15
[6]
6/6 ultraviolet rays A and / or B, among others.
Petition 870180014816, of 23/02/2018, p. 12/15
1/1
Relative humidity (%)
Time (min)

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AU2011335404B2|2017-02-02|

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MX358978B|2018-09-11|

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EP2646115B1|2017-11-08|

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WO2012072245A2|2012-06-07|

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JP6219166B2|2017-10-25|

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JP2013544309A|2013-12-12|

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BR112013013110A2|2016-07-12|

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KR20140024840A|2014-03-03|

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ES2390033B1|2013-10-31|

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法律状态:
2017-10-24| B07D| Technical examination (opinion) related to article 229 of industrial property law|

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2017-11-28| B06A| Notification to applicant to reply to the report for non-patentability or inadequacy of the application according art. 36 industrial patent law|

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2018-03-06| B09A| Decision: intention to grant|

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2018-05-02| B07G| Grant request does not fulfill article 229-c lpi (prior consent of anvisa)|

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2018-05-08| B16A| Patent or certificate of addition of invention granted|

优先权:

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申请号 | 申请日 | 专利标题

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ES201031775A|ES2390033B1|2010-11-30|2010-11-30|EXOPOLISACÁRIDO FOR THE TREATMENT AND / OR CARE OF SKIN, MUCOSAS, HAIR AND / OR NAILS.|

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PCT/EP2011/005996|WO2012072245A2|2010-11-30|2011-11-30|Exopolysaccharide for the treatment and/or care of the skin, mucous membranes, hair and/or nails|

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