Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
  • A61B18/02—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by cooling, e.g. cryogenic techniques
  • A61B18/0218—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by cooling, e.g. cryogenic techniques with open-end cryogenic probe, e.g. for spraying fluid directly on tissue or via a tissue-contacting porous tip
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin
  • A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
  • A61B18/02—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by cooling, e.g. cryogenic techniques
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
  • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
  • A61K8/69—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing fluorine
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
  • A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
  • A61B2018/00315—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body for treatment of particular body parts
  • A61B2018/00452—Skin
  • A61B2018/0047—Upper parts of the skin, e.g. skin peeling or treatment of wrinkles
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
  • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
  • A61K2800/87—Application Devices; Containers; Packaging
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
  • A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
  • A61K2800/95—Involves in-situ formation or cross-linking of polymers

Definitions

• TITLE Cosmetic composition intended for the treatment of cutaneous hyperpigmentation and method of treatment using said composition
• the invention applies to the field of cosmetics and relates, more particularly, to a cosmetic composition comprising a cryogenic fluid as well as to a process for treating cutaneous hyperpigmentation cryogenically using said composition. .
• Cryogenics is generally used in cosmetics to remove brown spots.
• Brown spots also called age spots, are small spots on the skin of varying size that appear on areas of skin exposed to the sun such as the face, hands, shoulders or arms. Dark spots are considered benign cosmetic deformities and are often unsightly. They are generally treated by cosmetic methods including the application of creams to the skin or by cryogenics.
• cryogenics Traditional methods of cosmetic treatment by cryogenics are implemented, for example, by means of a spray device providing local projections of a cryogenic fluid (liquid nitrogen, di-methyl-ether, di-fluoro- ethane, tetra-fluoro-ethane, etc. on the epidermis at negative temperatures in one or more freezing/thawing cycles.
• a cryogenic fluid liquid nitrogen, di-methyl-ether, di-fluoro- ethane, tetra-fluoro-ethane, etc.
• cyto-selective action so as to eliminate only the cells (melanocytes) responsible for cutaneous hyperpigmentations such as than brown spots, without producing any deleterious effect on other cells.
• This cyto-selective mode of action makes it possible to preserve, in particular, the keratinocytes because these cells are less sensitive to cold than melanocytes.
• the cyto-selective treatment of hyperpigmentation is obtained by a cryogenic sequence consisting of a succession of cycles comprising very rapid freezing followed by slow heating during which the destructive action of the melanocytes will be prolonged.
• a cryogenic sequence consisting of a succession of cycles comprising very rapid freezing followed by slow heating during which the destructive action of the melanocytes will be prolonged.
• the very sudden lowering of the temperature of the epidermis to a negative temperature generates, even before the cellular tissue is solidified, a micro-crystallization of the intracellular water which induces, at the same time, membrane alterations, denaturation of structural proteins and enzymatic systems, all conditions leading to a deleterious effect on the cell (cell lysis by mechanical shock).
• cryogenic devices such as the one described in patent application WO 2016/113305 intended for the implementation of a cyto-selective treatment of brown spots.
• This device ensures the controlled spraying (to the nearest hundredth of a second) of a cryogenic fluid intended to lower and maintain, for a few seconds, the temperature of the epidermis between -5°C and -20°C then to carry out a rise slow in temperature to obtain a lysis, that is to say a destruction, of the melanocytes and, consequently, an elimination of the brown spots.
• the device comprises a pressurized cryogenic gas cartridge having specific physical properties, a nozzle ensuring the delivery of a precise dose of cryogenic gas from the cartridge while being coupled to automated timing means and a nozzle intended to concentrate, diffuse and apply the flow of gas in a precise and homogeneous manner to a determined skin area.
• a nozzle is described, in particular, in FR3076200A1.
• the osmotic shock by differences in osmotic pressure gradient between the intra and extracellular media, will also cause the lysis of the melanocytes. Subsequently, within 2 to 4 weeks, which corresponds to the average cell renewal time, the body will gradually eliminate the cellular elements and melanin until the hyperpigmentation disappears completely.
• RAIDAN et al. [Raidan M et al. Effect of Cooling to Low Temperatures on Viability of Human Skin Keratinocytes at Different Stages of Differentiation. Cell and Tissue Biology, 2010, Vol. 4, No. 6, p. 1-10] conducted cell viability studies of cold-treated keratinocytes in a temperature range of -10°C to -70°C. The preservation of keratinocytes is essential because these cells have the ability to reform the different layers of the epidermis.
• BURGE et al. [Burge SM et al. Pigment changes in human skin after cryotherapy. Cryobiology, 1986, 23:422-432] showed that after a brief cooling of the skin for 5 seconds by a liquid nitrogen spray at -196°C over a margin of 1 to 5 mm beyond the lesion to be treated, hypo-pigmentation persists and that a 15-second extension of the application of cold caused the melanosomes to completely disappear in the keratinocytes.
• the viability of the melanocytes decreases by 40% compared to the control group (melanocytes not treated as a control group).
• FIG. 2 shows the viability of melanocytes as a function of the number of temperature oscillations produced on the cells.
• melanocytes subjected to 1 oscillation have a viability which decreases to 74.1% whereas melanocytes subjected to 4 consecutive oscillations see their viability decrease to 44%.
• oscillations could be applied through a sequence of successive sprays of a selected cryogenic gas intended to generate temperature oscillations on the surface of the epidermis.
• the invention makes it possible both to solve the technical problems posed by the prior methods and to overcome a technical prejudice.
• the invention shows that it is possible, contrary to the recommendations of the state of the technique considered, to obtain a strong reduction in the viability of the melanocytes as well as a lesser irritation produced by the keratinocytes (and therefore a effective elimination of cutaneous hyperpigmentation) using a cryogenic and cyto-selective cosmetic treatment characterized by a series of oscillations of the temperature of the epidermis, for very short durations, while maintaining the epidermis in a range of temperatures positive.
• a cosmetic composition intended for application to the epidermis for the treatment of cutaneous hyperpigmentation characterized in that it comprises from 1 to 7 doses of a sprayed cryogenic fluid whose boiling point is between -196°C and -19°C, each dose being between 0.048 mL and 0.56 mL.
• the invention has selected four specific formulations of this cosmetic composition, the effects of which are more particularly advantageous.
• the composition of the invention comprises a single dose of 0.08 mL of pulverized 1,1-difluoroethane.
• the composition comprises 4 doses of pulverized 1,1-difluoroethane, each dose being between 0.048 mL and 0.144 mL.
• the composition comprises comprises 2 doses of pulverized 1,1-difluoroethane, respectively, of 0.064 mL and 0.176 mL
• the composition comprises comprises 7 doses of pulverized 1,1-difluoroethane, each dose being between 0.40 mL and 0.56 mL.
• Another object of the invention is a method for preparing a cosmetic composition intended for application to the epidermis for the treatment of cutaneous hyperpigmentation, characterized in that it comprises the in situ formulation of 1 to 7 doses of a cryogenic gas, the boiling point of which is between -196°C and -19°C, by a sequence (EC) of successive sprays of said gas at a flow rate of between 0.1 mL/s and 2.0 mL/s, the respective durations of which are between 0.01 second and 1 second.
• a cryogenic gas the boiling point of which is between -196°C and -19°C
• Yet another object of the invention is a method for the cosmetic treatment of cutaneous hyperpigmentation by means of a pressurized cryogenic fluid cartridge and a device comprising a solenoid valve controlled by an electronic timing system and ensuring the expansion of the fluid from the said cartridge and a nozzle ensuring its ejection and its spraying on the epidermis, characterized in that a sequence of successive sprayings of the said fluid is carried out on the epidermis in order to create, in a range of temperatures positive, a series of oscillations of its temperature, the total duration of which is between 2.1 seconds and 250 seconds, each consisting of a sudden cooling phase at a temperature drop rate of between 50°C/s and 170°C/s followed by a slower heating phase.
• a composition for cosmetic use comprising a first dose of sprayed cryogenic gas which is applied for a very short time to the epidermis to lower its temperature to a target temperature (for example, +14°C, the epidermis being initially at 34°C). Then, one waits for its temperature to rise to its initial value (or to a lower value but still greater than or equal to 20°C) and this operation is possibly repeated several times (up to 7 times) by applying to the epidermis a new dose of fluid sprayed.
• a target temperature for example, +14°C, the epidermis being initially at 34°C.
• the doses are determined such that the temperature of the epidermis does not fall below 0° C.
• Each of these operations thus corresponds to an oscillation of the temperature of the epidermis.
• the invention has shown that the viability of melanocytes is dependent on the oscillations and a function of the number of oscillations and this up to 4 consecutive oscillations.
• the duration of each spray is between 0.01 second and 1 second.
• the duration of each of the oscillations is between 2.1 seconds and 3 seconds.
• the heating phase of the oscillations corresponds to a rise in temperature between 20° C. and 34° C.
• the number of successive oscillations of the temperature of the epidermis in a series is between 1 and 7.
• the temperature of the epidermis to be cooled to a target temperature of between 0° C. and 14° C.
• the epidermis cooling phase is carried out according to a gradient of at least 15° C. from an initial temperature of between 29° C. and 37°C (this temperature range covering the differences in temperature of the epidermis from one individual to another and according to the external environment).
• the cryogenic fluid is a gas whose boiling point is between -196° C. and -19° C.
• this cryogenic gas is chosen from the group consisting of 1,1-difluoroethane, the boiling point of which is -24.7° C. (under a normal pressure of 1 atmosphere or 1.013 bars), methoxymethane , 1,1, 1,2-tetrafluoroethane, trans-l,3,3,3-tetrafluoropropene, butane/propane mixtures having respective boiling points (under a normal pressure of 1 atmosphere or 1.013 bars), -196°C, -24°C, -26.3°C and -19°C (depending on the proportions of said mixture).
• said sequence is implemented by means of a single spray of 1,1-difluoroethane at 0.8 ml/second for a period of 0.1 second so as to achieve a target skin temperature of 14°C.
• the total duration of the oscillation comprising the drop in temperature of the epidermis then its rise towards a temperature of +20°C is 2.1 seconds.
• said sequence is implemented by means of 4 successive sprays of 1,1-difluoroethane at 0.8 ml/second each having a duration of between 0.06 second and 0.18 second to achieve a target skin temperature of 14°C after each spray.
• said sequence is implemented by means of 2 successive sprays of 1,1-difluoroethane at 0.8 ml/second having a duration of 0.22 seconds and 0.08 seconds respectively. to achieve a target skin temperature of 12°C after each spray.
• said sequence is implemented by means of 7 successive sprays of 1,1-difluoroethane at 0.8 ml/second each having a duration of between 0.5 second and 0.7 second so as to reach a target temperature of the epidermis of 0°C after each spray.
• This third variant of the method is implemented for a cumulative duration of the sprays of 3.9 seconds so as to reach a target temperature of the epidermis of 0° C. after each spray followed by a rise in temperature to at least minus 20°C.
• cryogenic fluid used in the cosmetic composition of the invention are successively sprayed and applied to the skin and, more specifically, to the epidermis, at regular and very close intervals.
• Such a sequence of sprays leads to phases of sudden cooling of the skin followed by pauses leading to phases of slower heating. These successive phases thus result in a series of oscillations in the temperature of the epidermis which correspond to a sequence of sprays of the cosmetic composition, within the meaning of the present invention.
• This spraying sequence consists of micro-sprays (or pulses), forming as many doses of cryogenic gas, interspersed with pauses.
• the EC14/4osc spray sequence comprises 4 sprays followed by breaks, the respective durations of which are indicated in table 2 below.
• a sequence is therefore characterized by a given number of sprays of cryogenic fluid and a corresponding number of oscillations in the temperature of the epidermis.
• These oscillations are independent of each other and each oscillation is itself defined, on the one hand, by a temperature gradient between a starting temperature (the epidermis being generally at 34°C) and a lower temperature but still positive (called target temperature) of the epidermis and, on the other hand, a kinematics of temperature descent whose speed is specifically between 50° C./s and 170° C./s resulting from the application of the cryogenic fluid.
• FIG. 1 is a graph illustrating various modes of implementation of the invention with the variations in the mortality rate of the melanocytes as a function of the temperatures applied according to different sequences.
• FIG. 2 is a graph illustrating various modes of implementation of the invention with the variations in the viability of the melanocytes as a function of a target temperature applied (+14° C.) according to several oscillations.
• FIG. 3 is a graph showing the variation over time of the irritation marker (IL-1b) for keratinocytes subjected to two sequences making it possible to reach the same level of viability, a sequence (EC16) located in a range of temperatures negative (-16°C) and the other sequence (EC14) in a positive temperature range (+14°C).
• IL-1b irritation marker
• FIG. 4 is a graph representing a preferred sequence of the cosmetic treatment process of the invention with temperature variations as a function of time in the form of a series of oscillations.
• FIG. 5 are graphs representing, respectively, the variations in the temperature of the epidermis as a function of time (curves in the lower part) in relation to a preferential sequence of sprays (top diagram) for the implementation of the treatment method of the invention.
• the invention relates to the field of cosmetic and cryogenic treatment of cutaneous hyperpigmentation and, in particular, the elimination of so-called brown spots which appear on the epidermis.
• a first part is linear and increasing and includes the sequences EC16 (at -16°C), EC-15 (at -15°C) and EC-10 (at -10°C), a second part is linear but in the form plateau and includes the sequences EC-05 (-5°C), ECO (at 0°C), EC+05 (at +5°C) and EC+10 (at +10°C) then a third part is again linear and increasing and includes sequences from EC+10 to EC+20 (at +20°C).
• the modification of cell viability occurs for very low temperature gradients, eg. from +15°C to +10°C (i.e. a gradient of 8°C in the case of experimentation on cell cultures, where the experimental conditions place the cells at a temperature of around 23°C during the experiment) .
• the rate of change in the temperature of the epidermis does not come into play either since the experiments showing variations in temperature, respectively, from +37° C. to +23° C. and from +23° C. at +10°C were carried out with high speeds of modification of the temperature gradients.
• cryogenics three kinetics of temperature descent are generally distinguished.
• a slow descent essentially corresponds to a lowering of 5°C/min, while a rapid descent takes place at 25°C/min and a so-called ultra-fast descent at 100°C/min.
• the mode of application of the cosmetic composition of the invention comprises, as illustrated by FIG. 4, a sequence of successive sprays of the cryogenic fluid intended to cause, in contact with the skin, an ultra-rapid drop in its temperature to starting from a noted starting temperature (T0) (generally 34° C.) up to a noted target temperature (Tl), ie a gradient (T0-Tl).
• T0 starting temperature
• Tl target temperature
• T0-Tl ie a gradient
• This temperature drop is carried out over a given period of time or duration (t) and therefore at a certain speed or kinetics (denoted Cl).
• cryogenic properties of the fluid used in the cosmetic composition of the invention as well as the functionalities of the device envisaged for preparing this composition in situ make it possible to perform, in the laboratory, a temperature drop of 23° C. (which is temperature of cell cultures when manipulated) to -15.8°C in 0.6 seconds, a rate of 76°C per second or 4560°C/min. It is therefore an ultra-fast cooling.
• the cosmetic treatment method of the invention consists in delivering a dose of cryogenic fluid, by means of the device previously described, with a view to obtaining a sudden lowering of the temperature of the cells of the epidermis with a strong gradient (for example, of 8° C.), while maintaining these cells in a range of positive temperatures.
• this process is not carried out by applying a single, high instantaneous dose of cryogenic fluid, which would present the risk of lowering the temperature of the epidermis below 0° C., but via several doses and typically , between 1 and 7 doses, depending on the formulation chosen.
• These doses are delivered and applied to the epidermis via a sequence of successive sprays of very short duration. This sequence thus produces oscillations in the temperature of the epidermis while remaining in a range of positive temperatures which make it possible to unexpectedly reduce the viability of melanocytes and therefore to treat cutaneous hyperpigmentation.
• the invention thus proposes a cosmetic composition whose doses (micro-volumes) are formulated in situ by means of a sequence of very short sprays (of duration typically between 0.01s and ls) comprising successive sprays of a cryogenic fluid for its immediate application to the epidermis.
• this composition makes it possible to lower, so periodically, the temperature of the epidermis initially at 34°C (and therefore that of the melanocytes) according to a temperature gradient greater than 15°C while maintaining in a controlled manner, during these temperature drops, the epidermis in a range of positive temperatures.
• the duration of the sprays, their number, their frequency and the intermediate pause times depend on the nature of the cryogenic fluid used, the flow rate of the solenoid valve used and other critical parameters.
• the duration of the sequence which comprises sprays spaced out with pauses is between 0.01s and 206 seconds (for 7 sprays), but is preferably less than 3.9s. It is clear that in all cases and because of the rise in temperature after each spraying, the durations of the sequences will be longer than the spraying times. According to the invention, provision is made for the duration of the series of oscillations for each sequence selected to be between 2.1s and 250s.
• a device suitable and intended for the in situ preparation of the cosmetic composition of the invention comprises a pressurized cryogenic gas cartridge having specific physical properties, a nozzle ensuring the delivery of a precise micro-dose of cryogenic gas from the cartridge by being coupled to automated timing means and a nozzle intended to concentrate, diffuse and apply the flow of gas in a precise and homogeneous manner to a determined skin area.
• One of the preferred modes of implementation of the treatment method of the invention making it possible to obtain the desired cosmetic result with respect to cutaneous hyperpigmentation comprises a sequence (referenced EC14) which consists in target, from a normal starting temperature of the epidermis of 34°C, an epidermis temperature of +14°C obtained with 4 consecutive sprays of cryogenic fluid.
• This sequence therefore thus comprises a series of 4 oscillations of the epidermal temperature.
• the opening times of the solenoid valve (EV) integrated in the cryogenic device used are those indicated in the following table 1:
• the volumes of gas sprayed each time the solenoid valve is opened can be calculated on the basis of the opening times given in tables 1 (above) and 2 (below) taking as a reference an average of the cryogenic gas flows at the outlet of the solenoid valve.
• the dosage or in other words, the doses of cryogenic fluid applied to the epidermis and making it possible to obtain the desired cosmetic effect goes as follows (cumulative of the successive volumes of fluid sprayed during a sequence) , from 0.08 ml with 1,1-difluoroethane gas (for the EC14 sequence with a single spray and therefore a single oscillation) to 3.50 ml (for the EC00 sequence with the same gas and 7 oscillations).
• the low (so-called target) temperatures of the epidermis, but still positive, obtained following the sprays referenced 1 to 4 (averages over 5 tests) are, respectively, 12.1° C., 13.6° C., 13.6°C then 13.0°C, the temperature rising with each oscillation above 20°C (see figures 4 and 5).
• each sequence (EC) is associated with a code indicating the target temperature and the number of oscillations.
• the sequences start with the solenoid valve (EV) in the closed position.
• the term (Pu) corresponds to the duration of an opening of the solenoid valve and therefore to spraying for a given time and at a flow rate fixed at 0.8 mL/s.
• the term (Pa) corresponds to the closing time of the solenoid valve between two sprays. This time corresponds to a pause (Pa) resulting in a natural rise in temperature of the epidermis above 20°C.
• the EC14/4 sequence is illustrated in Figures 3 and 5.
• the first objective of these experiments was to select cyto-selective sequences, that is to say, those which act only on the melanocytes by reducing their viability while preserving the keratinocytes (concept of performance) .
• a second objective was to determine the sequences which generated the smallest possible variation in the irritation markers (concept of risk). In summary, the sequences whose performance/risk ratio was optimal were selected.
• variants e.g. the EC+14/3osc sequence
• EC+14/losc and EC00/7osc both from the point of view of the positive target temperatures and of the number of oscillations, are of interest for the formulation of the cosmetic composition of the invention.
• Other studies which have been carried out on epidermis treated with the cosmetic composition of the invention confirm these results.

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• 2021
  • 2021-03-18 FR FR2102728A patent/FR3120792B1/fr active Active
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