Combination of active agents for treating skin aging
The present invention relates to the field of nutritional and/or cosmetic products which are particularly useful for preventing and/or treating the cutaneous signs of aging, including chronological aging and/or photoaging.
In mammals in general, particularly in humans, the skin consists of three compartments, namely a compartment which is in contact with the outside, the epidermis, a deeper compartment which serves as a support for the epidermis, the dermis and the more deeper hypodermis which harbors the skin fat tissue. The dermo-epidermal junction (DEJ) is an important transition zone between the epidermis and the dermis.
Among important skin molecules can be cited collagen, the most abundant protein in the skin which provides tensile strenght to the skin; elastin, a protein which forms elastic fibers in the dermis ; glycosoaminoglycans (GAGs), high volume-molecules which stock water for the skin ; and proteoglycans (PGs) which play a role in the organization of collagen and elastic fibers and which also ensure water retention.
While aging, structural and functional changes of dermal macromolecules occur, as explained below.
The collagen fibers are predominantly responsible for the strength and thickness of the dermis. They are constantly renewed, but this renewal decreases with age, which causes a reduction in the thickness of the dermis.
Although they are very resistant, collagen fibers are susceptible to certain enzymes called collagenases which form part of a family of enzymes called metalloproteinases (MMPs).
The MMP family is composed of several well defined groups based on their similarities in terms of structure and of substrate specificity. Mention may be made, among these groups, of collagenases intended to decompose fibrillar collagens (MMP-1 or interstitial coUagenase, MMP-8 or neutrophil coUagenase, MMP-13 or coUagenase 3, or MMP-18 or coUagenase 4), gelatinases which decompose collagen of type IV or any form of denatured collagen (MMP-2 or gelatinase A (72 kDa), or MMP-9 or gelatinase B (92 kDa), stromelysins (MMP-3 or stromelysin 1, MMP- 10 or stromelysin 2, or MMP-11 or stromelysin 3), the broad spectrum of activity of which applies to proteins of the extracellular matrix, such as glycoproteins (fibronectin, laminin), proteoglycans, and the
like, matrilysin (MMP-7), metalloelastase (MMP-12) or membrane metalloproteinases (MMP-14, MMP-15, MMP-16 and MMP-17).
Their overexpression in man and their activation are related, however, to numerous processes which involve the destruction and the remodeling of the matrix.
For example, prolonged exposure to ultraviolet radiation, particularly to type A and/or B ultraviolet radiation, has the effect of stimulating the expression of collagenases, particularly of MMP-1 and MMP-9. These are two of the components of photoinduced cutaneous aging. In addition, it is known that the activity of MMP-1, MMP-2 and MMP-9 increases with age and that this increase contributes, with a slow down in cell growth, to chronological aging of the skin.
As age-related dermal macro molecule modifications can be particularly cited collagen modifications such as decrease in collagen content, increase in type III/I collagen ratio, collagen fiber deterioration, and collagen netwok deterioration, elastin modifications such as decrease of elastin content and deterioration of elastic fibers, as well as GAGs and PGs modifications such as decrease of GAGs content, alteration of PGs composition and loss of water-binding capacity.
Indeed, as skin ages, it undergoes progressive structural modifications that have influence on the appearance and biochemical properties of the skin such as thickening of stratum corneum but global thinning of epidermis, flattening of DEJ, thinning of dermis, decrease of dermal density, disorganization of dermal network and decrease of skin hydration.
Hence, with age, progressively, the clinical signs of skin aging involve textural and volume changes such as loss of skin thickness, decrease in skin elasticity and wrinkles onset, and the skin loses firmness, becomes less dense, less elastic, and is less moisturized.
Those biological alterations of the matrix proteins and glucosaminoglycans result in more global changes in body skin and face appearance such as loss of tonicity, lack of density, deep folds, sagging and flaccidity together with a global skin dryness, wrinkling, depression and loss of plasticity, and firmness.
Furthermore, since the epidermis is relatively colorless not only skin melanocyte at the DEJ but also dermal matrix density, thickness and composition can also contribute to the global color and transparency of the skin. Thus biological alteration of the
skin matrix not only contribute to skin plasticity and hydration but can also contribute to some extent to global alteration of skin tone and color, radiance and transparency.
Thus, there is a need to provide novel active agents or a novel combination of active agents which are efficient both for preventing and/or treating chronological and photoinduced skin aging and more particularly for improving skin moisturizing (body and face), smoothness, firmness, suppleness and bouncy state on the face and the body.
There is also a need to provide novel active agents or a novel combination of active agents stable so as to prevent the degradation of the collagen fibers, to attenuate the wrinkles, to promote skin plumping, skin hydration and consequently skin radiance.
The present invention has the aim of satisfying these needs.
Thus, according to one of its aspects, a subject of the invention is the use of a combination comprising marine, porcine, bovine and/or any origin of collagen and vitamin B3 for having at least one of the beneficial effects on the skin chosen among attenuating the wrinkles, promoting skin plumping or bouncy state of the skin, promoting skin firmness and smoothness, promoting skin hydration and promoting skin radiance.
According to this aspect, the combination may have two, three or four of the hereabove cited effects simultaneously.
According to a further aspect, the present invention relates to a combination of active agents comprising at least one Silver Ear extract, collagen or a hydrolyzed form thereof, and vitamin B3.
According to one embodiment, the active ingredients are administered in a unique composition, in particular for oral administration.
According to another embodiment, the active ingredients are administered in distinct compositions. The active ingredients may then be administered simultaneously, independently from each other, separately or sequentially and during the same day.
To the inventors' knowledge, there has until now never been proposed or suggested that the administration to an individual in need thereof of a combination of active agents comprising at least one extract of Silver Ear, collagen and vitamin B3 could be particularly effective in the treatment of the cutaneous signs of aging including chronological and photoinduced aging, and useful for promoting skin plumping, skin moisturizing and skin radiance.
The expression « cutaneous signs of aging » is understood to mean any modification in the external appearance of the skin due to aging, whether it is chronological and/or photoinduced, such as for example, wrinkles and fine lines, withered skin, soft skin, skin with reduced thickness, dull skin and skin with no brightness, lack of elasticity and/or of tone of the skin, sagged skin, dehydrated skin, but also all the internal modifications of the skin which do not systematically result in a modified external appearance, such as, for example, all the internal damage to the skin, particularly to the collagen fibers, following exposure to ultraviolet radiation, which may have the consequence of reducing the thickness of dermis and mechanical properties.
The combination according to the present invention is formulated in compositions which are orally administrable. This has the advantage of acting globally on the entire skin, in its deep layers (dermis, hypodermis), by means of a rapid and relatively non-restrictive mode of administration. Specifically, the metabolites and other active nutriments are in particular distributed within the dermal matrix by means of the bloodstream. Oral administration also has the advantage of a rapid and relatively non- restrictive mode of administration.
More particularly, the oral administration of a combination according to the invention allows improving skin moisturizing (body and face), smoothness, firmness, suppleness and bouncy state on the face.
More particularly, the oral administration of a composition according to the invention allows preventing the degradation of the collagen fibers, to attenuate the wrinkles, to promote skin plumping, skin hydration and consequently skin radiance.
More particularly, the oral administration of a combination according to the invention allows preventing collagen modifications such as decrease in collagen content, increase in type III/I collagen ratio, collagen fiber deterioration, and collagen network deterioration.
More particularly, the oral administration of a combination according to the invention allows preventing elastin modifications such as decrease of elastin content and deterioration of elastic fibers.
More particularly, the oral administration of a combination according to the invention allows preventing GAGs and PGs modifications such as decrease of GAGs content, alteration of PGs composition and loss of water-binding capacity.
More particularly, the oral administration of a combination according to the invention allows reducing the thickening of stratum corneum, thinning of epidermis, flattening of DEJ, thinning of dermis, decrease of dermal density, disorganization of dermal network, and decrease of skin hydration.
« Plumping » means according to the invention to increase the volume and / or thickness of the skin and / or smooth and / or give it a swollen appearance.
« Skin radiance » according to the invention is an indication of the healthy condition of the skin. More particularly a luminous, radiant, or even glowing complexion is indicative of skin in good condition.
According to one of its aspects, the present invention concerns a nutritional or cosmetic composition for an oral administration comprising at least collagen, preferably marine collagen, or a hydrolyzed form thereof, vitamin B3 and one Silver Ear extract.
According to another of its aspects, the present invention relates to a cosmetic use of a combination according to the present invention for preventing and/or treating the cutaneous signs of aging, including chronological aging and/or photoaging, in particular attenuating wrinkles and/or for improving skin moisturizing or hydration, and/or promoting skin plumping and/or for promoting skin radiance.
For the purposes of the present invention, the term « prevention » or
« preventing » means to remove completely or to partially reduce the risk of manifestation of a given phenomenon, that is to say, in the present invention, the cutaneous signs of aging, including chronological aging and/or photoaging. The partial reduction implies that the risk remains, but to a lesser degree than before the implementation of the invention.
According to another of its aspects, the present invention relates to a cosmetic process for preventing and/or treating the cutaneous signs of skin aging, including chronological aging and/or photoaging, and more particularly attenuating the wrinkles, and/or for improving skin moisturizing or hydration and/or for promoting skin radiance, and/or for promoting plumping of the skin in an individual in need thereof, comprising at least the oral administration to said individual of a combination according the invention or of a composition according to the invention.
According to a further of its aspects, the present invention relates to a kit comprising:
(i) a first composition for oral administration comprising at least one collagen, preferably marine collagen and vitamin B3, and
(ii) a second composition for topical administration comprising at least one moisturizing agent and preferably a Silver Ear extract.
COLLAGEN
Collagen may be of various origins, i.e. porcine collagen, bovine origin, marine origin or any other origin suitable for human administration.
According to a particular embodiment, collagen is marine collagen.
As far as marine collagen is concerned, also known as fish collagen, it is a material derived from the substance found on fish scales.
More particularly, fish collagen may be produced from the skin of deep water, ocean fish such as cod, haddock, hake, pollock, dab, Japanese bass and tuna.
In a combination according to the invention, either native or hydrolyzed marine collagen may be used.
In a preferred embodiment, hydrolyzed marine collagen is used in the combination according to the invention.
Hydrolyzed collagen is produced by hydrolysis of the collagen found in the connective tissue of fish.
Fish hydrolyzed collagen may have a specific amino acid profile, with particular glycine, proline/hydroxyproline, and glutamic acid contents.
A hydrolyzed marine collagen which may be suitable for the present invention is a collagen extract composed of type I hydrolyzed collagen from fish origin, with a process rigorously controlled to obtain a precise degree of hydrolysis and specific aminoacids composition.
Said hydrolyzed marine collagen may be produced by hydrolysis of the collagen from fish skin into water soluble peptides. This marine hydrolyzed collagen may for example contain 20% glycine, 20% proline/hydroxyproline and 11% glutamic acid.
For example, a hydrolyzed marine collagen which is suitable for the present invention may also be obtained via a biochemical treament in the presence of a protease, may be submitted previously to a mechanical treament so as to obtain it in a form of powder, or may be submitted to a deodorizing treatment via a heating treatment.
By way of example, hydro lyzed fish collagen marketed by the Rousselot company (Angouleme plant, in France) under the names Peptan™F, Peptan™F 2000 HD and Peptan™F 5000 HD may be used in a composition according to the invention.
More precisely, the hydro lyzed fish collagen from Rousselot company is made from fish skin coming from tilapia, pangasus, tuna and/or Nile perche and the fishes may come from Costa-Rica, Ecuador, European Union, Ghana, Honduras, Indonesia, Ivory Coast, Malaysia, Thailand, Uganda, Tanzania and Vietnam.
A further advantage of marine collagen is to stabilize a composition suitable for the invention.
A composition according to the invention advantageously comprises from
0.1% to 60%) by weight, preferably from 1% to 50%> by weight and even more preferentially from 1% to 40% by weight of marine collagen, hydro lyzed or not, relative to the total weight of the composition.
The doses of collagen made to achieve the objects of the invention may be adjusted according to the desired effect. For example, it may be provided a dose ranging from 0.1 to 20 g/day, preferably 0.5 to 15 g/day, and preferably from 1 to 9 g/day.
VITAMIN B3
Vitamin B3 is a water-soluble compound with the formula C6H5NO2 and is also known as nicotinic acid, vitamin PP (for Pellagra Preventive), or niacin. Its amide form is named Nicotinamide (niacinamide). Both are similarly effective and can be converted into each other within the organism.
Vitamin B3 is present in most of foods, but exists in particularly high quantities in meat, fish, cereals and mushrooms.
By way of example, Vitamin B3 which may be suitable for the present invention is marketed under the name Niacinamide PC by the DSM company.
A composition according to the invention advantageously comprises from 0.0001%) to 1%) by weight, preferably from 0.0005%) to 0.5%> by weight and even more preferentially from 0.001% to 0.1% by weight of vitamin B3 relative to the total weight of the composition.
The daily amount of Vitamin B3 is from 0.01 to 30 mg/day, preferably from 0.05 to 25 mg/day, still more preferably from 0.1 to 20 mg/day.
SILVER EAR EXTRACT
Silver Ear is also called White Jelly Fungus (WJF), white fungus, Tremella fuciformis, snow fungus, silver ear fungus or white jelly mushroom.
WJF is a translucent white or even better light yellowish- white jelly fungus that grows on deciduous trees such as oak, maple, poplar, willow in warm and temperate climates worldwide.
Tremella fuciformis berk belongs to the Tremellaceae family of the class heterobasidiomycetes. The fungus is known as a nutritious mushroom and an important medicine for people in China.
A variety of semi-purified polysaccharides have been isolated and characterized from the Tremella fuciformis fruiting bodies which are an acknowledged source of non-starch polysaccharides, namely (l->3)-P-D-glucans consisting of a (1->3)-α- mannan backbone with small xylose- and glucuronic-containing side chains.
Silver Ear is a natural source of so-called botanical polysaccharides.
More precisely, a Silver Ear extract which is suitable for the present invention is obtained from the Oryza oil & Fat Chemical Co, ltd. Company (nom commercial White Jelly Fungus Extract).
Indeed, Oryza Oil & Fat Chemical Co. Ltd has extracted polysaccharide from white jelly fungus, which is provided as White Jelly Fungus Extract. Composed of at least 80% total saccharides and 10-30%) glucuronic acid, White Jelly Fungus Extract is a food item with a supple texture. It sucks water and swells, and gives rise to a large volume of highly viscous transparent solution.
By way of example, 60 kg of raw material is needed to obtain 1 kg of extract (plant/extract concentration ratio 60: 1).
A composition according to the invention advantageously comprises from 0.001%) to 5%) by weight, preferably from 0.01% to 5% by weight and even more preferentially from 0.01% to 3% by weight of Tremella fuciformis extract relative to the total weight of the composition.
The daily amount of Silver ear is from 1 to 3000 mg/day, preferably from 5 to 2000 mg/day, still more preferably from 10 to 300 mg/day.
In a preferred embodiment, when the composition is under the form of a beverage, the selected dose of silver ear extract is of 30mg / 50ml drink.
ADDITIONAL ACTIVE AGENTS
A combination according to the invention may also comprise at least one further active cosmetic agent.
Advantageously, such active cosmetic agent can be used to enhance the cosmetic effect as described above.
By way of illustration, mention may be made of vitamins such as vitamins A, C, D, K, Bl, B2, B3, B5, B6, B8, B9, B12 and E, minerals such as zinc, copper, magnesium, and selenium, essential fatty acids, trace elements, polyphenols, flavonoids, nutritional active anti-aging agents, for example dietary antioxidants, nutrients with anti- free radical enzymes and cofactors endogenous antioxidants, antioxidants such as lipoic acid and coenzyme Q10, superoxide dismutase (SOD), resveratrol, curcuminoids, taurine, carotenoids, xanthophylls, prebiotics, probiotic microorganisms, hyaluronic acid, proteins and amino acids.
Among the anti-ageing active agents, mention may be made especially of unsaponifiable fractions extracted from fats of plant origin, Aloe vera, and plant or marine oils rich in omega-3 and omega-6 fatty acids (including gammalinolenic acid), photoprotective active agents.
The skilled person should select the additional active agents and the amount thereof such that the advantageous properties of the composition according to the invention are not, or are not substantially, adversely affected by the envisaged addition. COMPOSITIONS AND KIT
According to one aspect of the invention, a combination of active agents suitable for the invention can be implemented in a cosmetic composition adapted for oral administration.
The three main active agents which are suitable for the present invention, that is to say Silver Ear extract, collagen or a hydrolyzed form thereof, and vitamin B3 may be administered simultaneously, separetely or sequentially.
A composition according to the invention comprises a physiologically acceptable medium.
According to the invention, the term "physiologically acceptable medium" is understood to mean a medium devoid of toxicity and compatible with oral use and food safety
A combination of active agents according to the invention or a composition according to the invention is orally administered.
As mentioned previously, the oral administration has the advantage of acting globally on the entire skin, in its deep layers (dermis, hypodermis), by means of a rapid and relatively non-restrictive mode of administration.
An effective amount of a combination according to the invention or of a composition according to the invention may be administered in a single dose per day or in fractional doses over the day, for example two to three times a day.
An oral process may be performed over a time period ranging from one week to several weeks, or even several months, this period moreover possibly being repeated after periods without treatment, for several months or even several years.
By way of example, the oral administration of a composition according to the invention may be performed at a rate, for example, of 2 times a day or more, generally over a prolonged period of at least 4 weeks, or even 4 to 15 weeks, optionally comprising one or more periods of stoppage or being repeated after a period of stoppage.
According to the invention the expression "cosmetic oral composition" means, for example, nutritional, nutraceutical, or cosmeceutical compositions comprising at least one combination according to the invention.
In the framework of the present invention, "food complement" or "food supplement" have the same meaning, i.e. a composition for oral administration which is taken separately from the normal diet of a human being, i.e. which cannot be confused with his food, aiming at providing complementary nutriments or active ingredients to him for implementing beneficial effects for his well-being or beauty.
In the framework of the present invention, "health food" means food considered to be beneficial to health such as enriched and fortified foods with vitamins and minerals.
Thus, the use of an ingestible support or carrier within the composition comprising said combination according to the invention is preferred.
The ingestible support or carrier may be of diverse nature depending on the type of composition under consideration.
For ingestion, many embodiments of oral compositions including, food, food supplements and health food are possible.
In other words, a composition according to the invention may be a food, a food composition or food supplement or may be a health food for human consumption.
The formulation of such compositions can be produced by any conventional method known by the man skilled in the art.
Thus, a composition according to the invention may take the form of a food supplement, and for example a coated tablet, for example sugar-coated tablet, a liquid suspension or solution, a gel, a hydrogel, an emulsion, an oral solution, a flavored drink, tablet to swallow or chew, a capsule, especially a soft or hard capsule, a phial, granules or powder to be dissolved or a syrup.
The oral compositions may be either in anhydrous or aqueous form.
In particular, a combination of active agents according to the invention may take the form of compacted or non compacted powders. The powders may be diluted in water.
According to one embodiment, a composition according to the invention administered orally, may be formulated in the form of a food which may take the following form: compact or loose powders, beverages (refreshing drinks, flavored drink, lactobaciUus beverage, etc.), milk or fermented milks or fermented soymilk.
As health food, for example, milk, fermented milk, fermented products made from milk, food supplements in dry form and food supplements in liquid form may be suitable.
The active agents according to the invention may moreover be formulated with the usual excipients and components for such oral compositions or food supplements, i.e. in particular fatty and/or aqueous components, humectants, thickeners, preservatives, texturing agents, flavour enhancers and/or coating agents, antioxidants, preservatives and dyes that are customary in the food sector.
The formulating agents and excipients for oral compositions, and in particular for food supplements, are known in this field and will not be the subject of a detailed description herein.
Preferably, a combination or a composition according to the invention, administered orally, is formulated in the form of a beverage, a drink, a stick-gel, or a powder to be diluted in a liquid such as water or fruit juice, vegetable juice, and more preferably in the form of a drink.
Any of the additional active agents as previously described may be added to a composition in accordance with the invention.
The support or carrier may be of various natures, depending on the type of composition under consideration.
A combination according to the invention or a composition according to the invention is useful for preventing and/or treating the cutaneous signs of aging, including chronological aging and/or photoaging, for skin regeneration and repair, for improving the quality of the skin, for dermal matrix skin protection, for reducing or preventing wrinkles and/or fine lines, withered skin, slackened skin, lack of skin elasticity and/or tonicity, thinning of the dermis, degradation of collagen fibres, flaccid skin, thinned skin and any internal degradation of the skin, for improving and/or reducing the microrelief of the skin and/or for maintaining and/or improving the barrier function of the skin, for maintaining and/or reinforcing the epidermis and/or the dermis, or for maintaining the integrity and/or thickness of the various layers of the skin, for making the skin smooth, for improving the mechanical properties of the skin and/or for promoting skin repair, for improving the density and/or firmness of the skin, and/or for increasing the synthesis of collagens, for making the skin supple, for moisturizing the skin, for improving skin smoothness, firmness, suppleness and bouncy state on the face, for promoting skin plumping, skin transparency and skin radiance and to prevent more global changes in body and face skin appearance such as loss of tonicity, lack of density, deep folds, sagging and flaccidity together with a global skin dryness, wrinkling, depression and loss of plasticity, and firmness.
In particular, the combination according to the present invention, composition according to the present invention or kit according to the present invention is useful for attenuating wrinkles and/or promoting skin plumping or bouncy state of the skin and/or
promoting skin firmness and skin smoothness and/or promoting hydration and/or promoting skin radiance.
The wrinkles, are in particular those which lay out radially around the mouth and/or of the eyes, in particular the wrinkles of the crow's feet, the wrinkles under the eye and/or located at the level of the face, in particular the wrinkle known as of glabelar lines, located at the level of gabelle, in space inter-sourcillier, and/or horizontally laid out on the face, the wrinkles of the furrow nasogenien, and the ptose of the bottom of the face.
As far as the kit is concerned, according to one embodiment, said compositions (i) and (ii) comprised in a kit in accordance with the invention may be administered, independently from each other, simultaneously, separately or sequentially.
Any moisturizing agent may be present in the composition (ii) and preferably a Silver Ear extract, and any of the additional active agents as previously described may also be added to a kit in accordance with the invention.
The topical composition (ii) can advantageously be formulated in any dosage form suitable for the care of the skin and mucous membranes and may be in the form of ointments, creams, milks, ointments, powders, impregnated pads, solutions, gels, sprays, lotions or suspensions. It can also be in the form of microspheres or nanospheres or of lipid or polymeric vesicles or of polymeric patches and hydrogels for controlled release. This composition for topical administration can be either in anhydrous form or in aqueous form as an indication dermocosmetics.
A composition for administration by the topical route may be an aqueous, hydro alcoholic or oily solution or dispersion of the lotion or serum type, emulsions of liquid or semi-liquid milk type, obtained by dispersion of a phase fat in an aqueous phase (O/W) or conversely (W/O), a suspension or an emulsion, a soft, semi-solid or solid, of the cream or gel-like aqueous or anhydrous, a multiple emulsion (E/O/W or 0/W/O), a microemulsion, a nanoemulsion, a microcapsule preparation, a preparation of microparticles, or a vesicular dispersion of ionic and / or nonionic surfactant, or a wax / aqueous phase.
According to a preferred embodiment, a topical composition may be in the form of a solution, a cream, a gel, an emulsion, foam or an aerosol composition containing a propellant.
According to a preferred embodiment, a topical composition may also be in the form of a transdermal system to release active or passive / active in (s) by transdermal route e.g. patch type or gel patch type (hydrogel).
These compositions are prepared according to conventional methods.
PROCESS
According to another of its aspects, the present invention relates to a cosmetic process for preventing and/or treating the cutaneous signs of skin aging, including chronological aging and/or photoaging, and more particularly attenuating wrinkles, and/or for improving skin moisturizing or hydration and/or for promoting skin radiance, and/or promoting skin plumping of the skin in an individual in need thereof, comprising at least the oral administration to said individual of a combination or of a composition according to the invention.
A process according to the invention may be implemented on a daily basis for example, due for example to a single dose per day or twice daily administration, for example, once in the morning and once in the evening, or three times a day, including meals.
A cosmetic process according to the invention can be implemented, for example by daily administration of a composition formulated for example as capsules, coated tablets, flavored drink, emulsions, tablets, capsules or phials, in adequate amount and number, according to their formulation.
An effective amount of a combination according to the invention may be administered in a single daily dose or in divided doses throughout the day, such as two to three times a day doses.
A process according to the invention may advantageously comprise a single administration.
A cosmetic process can be implemented over a period of time ranging from one week to several weeks or months, this period may also be repeated after periods of non-treatment for several months or even several years.
For example, the administration of a combination of active agents according to the invention can be carried out, for example, two times a day, usually over a prolonged
period of at least 4 weeks or even 4 to 15 weeks, optionally comprising one or more periods of interruption or being repeated after a period of interruption.
In the description and in the examples that follow, unless otherwise indicated, the percentages are percentages by weight and the ranges of values written in the form "between . . . and . . . " include the upper and lower limits specified.
The ingredients are mixed, before being formulated, in the order and under conditions that can be readily determined by those skilled in the art.
The content and the nature of the ingredients used in the compositions of the invention are adjusted by those skilled in the art in such a way as not to substantially affect the properties required for the compositions of the invention.
The following examples are presented for illustrative purposes and do not limit the scope of the invention.
EXAMPLES
Example 1 : anti-aging drink
This composition is available in the form of a drink of 50ml.
This drink is to be drunk once to three times per day during from seven days to three months.
Renew the cures, if necessary.
This drink is useful for preventing and/or treating skin aging and particularly allows improving skin firmness, skin hydration, skin radiance and skin smoothness.
Example 2: drink
Combination of white fungus extract (Silver ear), extract of fish collagen and Vitamin B3 allows to limit the activation of MMPl and MMP9 by UV and more particularly allows to improve skin radiance and skin hydration.
This drink is to be drunk from 15 days to 1 month before, then during and after sun exposure.
Example 3 : stick (water dispersible powder)
This stick is diluted in a glass containing water or fruit juice and is absorbed two times a day.
This stick-gel is useful for improving the quality of the skin, and more particularly for reducing wrinkles and fine lines, for improving skin elasticity and tonicity.
Example 4: clinical evaluation on the combination marine collagen and vitamin
B3
A clinical evaluation was performed on 105 volunteers (30-45 years old Asiatic women with a BMI ranging from 19 to 26 kg/m2) to assess the effects of a combination of collagen and vitamine B3 under the form of a flavored beverage on skin qualities.
The average age was 37.20 ±3.5
The average BMI was 22.10 ± 1.8
Statistical analysis
•Supplementation period: performed on 101 volunteers (4 volunteers were drop out between their visits TO and Tl month for personal reasons).
• Follow-up period: performed on 96 volunteers.
Protocol
Active ingredients:
Marine fish collagen : 3 333.33 mg/bottle
- Vitamin B3 : 0.40 mg/bottle
Excipients / Additives: water, sweeteners, citric acid, flavors
Direction for use: 1 bottle (mini-drink) per day, to drink at once or consume soon after opening, in the morning. Better when chilled. Shake before use.
The following criteria have been assessed at each time point: TO, Tl, T2 and T3 months, using clinical and self-assessments (whole population):
o Skin firmness (face)
o Skin moisturizing (face and whole body : global evaluation from the 2 forearms and legs)
o Skin suppleness (face)
o Skin smoothness (face)
o Bouncy state (face)
o Skin radiance (face)
o Visibility of first wrinkles (face)
The following criteria have been assessed at Tl, T2 and T3 months, using overall-assessment by the subjects (whole population):
o Skin comfort
o Make-up application
o Skin strength
o Young aspect of the skin
o Healthy condition of the skin
o Rosy glow
o Homogeneity of skin complexion
The following criteria have been assessed at follow-up T2 weeks and follow-up T4 weeks visits using follow-up overall assessment questionnaire (population concerned with the follow-up period):
o Skin firmness (face)
o Skin moisturizing (face and whole body: global evaluation from the 2 forearms and legs)
o Skin suppleness (face)
o Skin smoothness (face)
o Bouncy state (face)
o Skin radiance (face)
o Visibility of first wrinkles (face)
o Skin comfort
o Make-up application
o Skin strength
o Young aspect of the skin
o Healthy condition of the skin
o Rosy glow
o Homogeneity of skin complexion
Subjects have had to answer different questions concerning the efficacy of the investigational product 2 weeks (T2 weeks) and 4 weeks (T4 weeks) after the stop of the investigational product intake, in standardized conditions, using 6-point scales: "definitely agree", "really agree", "rather agree", "rather disagree", "really disagree" and "definitely disagree".
Results
A. Effect on skin qualities
Scores were attributed to the various tested criteria. Evaluation was performed by both the dermatologist and the volunteers. (n=101 volunteers)
"ITT population" means Intent To Treat Population.
A.1 Clinical evaluation
The evolution of the parameters was compared using a Wilcoxon test on paired data with a threshold of significance fixed at 5%, on the ITT population.
The dermatologist had to score from 1 to 10, "1" being the best score and "10" the worse score. An improvement is represented by a decrease of the mean score.
A result was considered as clinically relevant if the evolution was statistically significantly different from baseline (p<0.05) and if the evolution was of 1 score at least.
The number of "responders" was calculated for each time (a "responders" is defined as a subject with an improvement of 1 score at least between 2 times).
1. Clinical evaluation: mean values and evolutions versus baseline (ITT population)
In bold: clinically relevant results / imp: improvement/det: deterioration
2. Clinical evaluation: percentage of evolution and percentage of "responders" (ITT opulation)
Skin radiance
+5.4% +1.5% -8.8% 24.8% 28.7% 42.6% (face)
First wrinkles
-4.0% -7.5% -1 1.3% 34.7% 42.6% 51.5% visibility (face)
In bold: percentages that can be considered as relevant considering the mean evolution scores.
A.2 Self-Assesment
The evolution of the parameters was compared using a Wilcoxon test on paired data (for not normally distributed variables) or using Student test on paired data (for normally distributed variables), both with a threshold of significance fixed at 5%, on the ITT population.
The subject had to score from 1 to 10, "1" being the best score and "10" the worse score. An improvement is represented by a decrease of the mean score.
A result was considered as clinically relevant if the evolution was statistically significantly different from baseline (p<0.05) and if the evolution was of 1 score at least.
The number of "responders" was calculated for each time (a "responders" is defined as a subject with an improvement of 1 score at least between 2 times).
1. Self-assessment: mean values and evolutions versus baseline (ITT population)
In bold: clinically relevant results / imp: improvement / w: Wilcoxon test on paired data / St: Student test on paired data.
2. Self-assessment: percentage of evolution and percentage of "responders" (ITT opulation)
In bold: percentages that can be considered as relevant considering the mean evolution scores.
A.3. Conclusion
Both the dermatologist and the volunteers observed relevant improvements in skin qualities:
After 1 month of supplementation: in skin moisturizing on the face. After 2 months of supplementation: in skin moisturizing, skin smoothness, skin firmness, suppleness and bouncy state on the face.
After 3 months of supplementation, relevant improvements were observed by both the dermatologist and the volunteers for skin moisturizing (face and body), smoothness, firmness, suppleness and bouncy state on the face.
B. Overall clinical efficacy score
The overall clinical efficacy was measured by anylising the responses to the following question: « The tested product improved »:
% of « satisfied » volunteers (= % of « definitely agree » + % of « really agree » + % of « rather agree »)
n=101 volunteers
1. Overall assessment: detailed descriptive statistics (%, n)
"Definitely agree" 6.9% (7) 11.9% (12) 12.9% (13)
"Really agree" 31.7% (32) 34.7% (35) 37.6% (38)
Young aspect of
the skin "Rather agree" 51.5% (52) 49.5% (50) 48.5% (49)
"Satisfied
90% (91) 96% (97) 99% (100) subjects"
"Definitely agree" 5.0% (5) 9.9% (10) 11.9% (12)
"Really agree" 39.6% (40) 44.6% (45) 55.4% (56)
Healthy condition
of the skin "Rather agree" 52.5% (53) 44.6% (45) 30.7% (31 )
"Satisfied
97% (98) 99% (100) 98% (99) subjects"
2. Overall assessment: detailed descri tive statistics (%, n)
3. Overall assessment: descriptive statistics (%, n) and evolution
the skin "Unsatisfied
3% (3) 1 % (1 ) 2% (2)
subjects"
"Satisfied
82% (83) 86% (87) 92% (93)
subjects" p=0.021 p=0.031
Rosy glow p=0.39
"Unsatisfied imp imp
18% (18) 14% (14) 8% (8)
subjects"
"Satisfied
Homogeneity 90% (91 ) 91 % (92) 97% (98)
subjects" p=0.039
of skin p=1.0 p=0.07
"Unsatisfied imp complexion 10% (10) 9% (9) 3% (3)
subjects"
In bold: statistical significant results / imp: improvement
4. Conclusion
The percentage of satisfied volunteers increased over the supplementation period. After 3 months of supplementation more than 92% of the volunteers were satisfied for all efficacy criteria.
It is moreover to be noted that more than 86% of the volunteers who declared to be satisfied with the tested product at the end of the 3-months supplementation period, reported that the benefits of the investigational product remained visible 2 and 4 weeks after supplementation stop, on all the assessed parameters.
C. Follow-up assessment
After a 3 -month supplementation period, 96 subjects were satisfied with the supplementation and continued with a follow-up period of 4 weeks without any supplementation. They assessed the persistent efficacy of the supplementation 2 and 4 weeks after supplementation stop.
For each parameter, the results below represent the percentage and number of subjects for each of the 3 possible answers ("definitely agree", "really agree", "rather agree").
The percentage of "satisfied subjects" corresponds to the addition of the 3 possible answers related to a "satisfaction" ("definitely agree", "really agree", "rather agree").
1. Follow-up assessment: detailed descriptive statistics (%, n)_l/2
2. Follow-up assessment: detailed descriptive statistics (%, n)_2/2
2 weeks after supplementation stop, from 88 to 99% of the subjects reported that benefits remained visible.
4 weeks after supplementation stop, this proportion decreased slightly but remained high (from 86 to 98%> of the subjects).
D. Macrophotographs analysis
Rz max parameter corresponds to the difference between the "higher" and the "lower" points, i.e. between extremes. A decrease of this height means the skin is smoother and the wrinkles less deep.
Ra parameter measures the mean roughness (arithmetic) on the overall photograph. Lower is Ra value, smoother is the surface of the skin.
Rq parameter measures the quadratic roughness on the overall photograph. It gives more importance to extreme points. Lower is Rq value, smoother is the surface of the skin.
Skewness parameter measures the surface asymmetry. A skewness value =0 means skin surface is perfectly symmetrical. A skewness <0 means skin surface is composed of large plateaus with fissures. A skewness >0 means that the surface of the plateaus decreases. An increase of skewness parameter is related to a decrease of the plateaus, i.e. a younger skin surface.
Macrophotographs analysis
In bold: statistical significant results / imp: improvement / w: Wilcoxon test on paired data / St: Student test on paired data.
Comments:
Ra and Rq parameters did not change significantly after 3 months of supplementation.
While the difference is not statistically significant (p=0.06), skewness parameter increased between TO and T3 months.
Rz max parameter decreased statistically significantly after 3 months of supplementation (p=0.031).
While this effect is not visible by human eye, this results means the skin may be smoother after a 3 -month supplementation period. After 3 months, the difference between the highest point and the lowest one was decreased, so the amplitude of the relief of the skin too. The first action of a supplementation on the relief will be to decrease the maximal superior and inferior points then to reduce the whole set of extreme points then to decrease all the points. Usually an oral supplementation acts from the depth of the skin so it is usually observed a first action on the deeper furrows. The action on the picks is more characteristic of topical products.
Figure 1 represents macrophotographs (subject n°015), which are an example of illustration of what happens in depth. They only are examples and do not represent the effects on the whole population of the study. This effect is not visible by human eye.