CARBOXY THERAPY DEVICE WITH HOLLOW MICRO-NEEDLE

Abstract

The invention relates to a device (100), particularly a cosmetic one, for the subcutaneous injection of gas, in particular carbon dioxide (CO2), comprising a gas reservoir (10) in fluidic communication with a hollow microneedle (4) via a distribution line (20), and including a purging system (22) for evacuating residual gases present in the microneedle. [Fig. 1]

Description

Title of the invention: CARBOXYTHERAPY DEVICE WITH HOLLOW MICRO-NEEDLE

[0001] The present invention relates to a device, in particular a cosmetic device, for injecting gas under the skin, in particular carbon dioxide, comprising a hollow micro-needle. It also relates to a cosmetic method using this device.

[0002] The gases that can be injected in accordance with the invention are in particular chosen from biocompatible gases such as CO2, N2O, NO, O2, H2. Advantageously, the gas injected according to the invention is CO2.

[0003] More generally, a cosmetic product is a product as defined in Regulation EC No. 1223 / 2009 of the European Parliament and of the Council dated November 30, 2009, relating to cosmetic products. Technological background

[0004] It is known to use injectable cosmetic fillers to reduce facial wrinkles and restore volume and fullness to the face.

[0005] As we age, faces naturally lose subcutaneous fat.

[0006] The facial muscles then work closer to the skin's surface, so that smile lines and crow's feet, for example, become more apparent.

[0007] The facial skin also stretches a little, adding a loss of facial volume.

[0008] Other factors that affect facial skin include sun exposure, heredity, and lifestyle.

[0009] The Stratum Corneum (SC) constitutes the main barrier of the epidermis to exogenous substances, including compositions of small and high molecular weight biopolymers used as cosmetic fillers.

[0010] Techniques for eliminating the SC barrier, such as stripping and aspiration, laser or thermal ablation are not practical, while needle-free injections have so far failed to replace known needle-based administration. Such a delivery method can be uncomfortable, even painful, due to the shape of the needles, and the viscosity of the composition, such as compositions comprising hyaluronic acid, and is therefore unsightly for users.

[0011] Dark circles are a common expression feature among the population. The appearance of dark circles, aggravated by physiological aging of the face, affects men and women of all ages and often constitutes a significant aesthetic concern due to the tired appearance they bring to the eyes.

[0012] The thinness of the skin tissue is probably the main reason for the darker skin around the eyes. This thin skin reveals the veins and capillaries underlying, giving the area a bluish, even purplish, or grayish color. This coloration is aggravated in cases of vascular congestion and lack of oxygenation in the periorbital area. In addition, as the skin ages, the lipid layer under the eyes sags and swells, creating shadows and thus making this area even darker. A second frequently found cause is excessive pigmentation of the skin, whether spontaneous or environmentally induced

[0013] The challenge is a comprehensive management of dark circles including the improvement of skin coloration, for which injections (of hyaluronic acid for example) alone have not demonstrated effectiveness. Laser treatments and chemical peels exist but are generally very aggressive and accompanied by significant adverse effects.

[0014] Carboxytherapy consists of a subcutaneous injection of carbon dioxide (CO2), very frequently targeting the dermis or hypodermis. The injected CO2 creates hypercapnic stress which increases the transcutaneous oxygen pressure (tc-PO2) thanks to three phenomena; an increase in capillary blood flow; a reduction in cutaneous oxygen consumption caused by the vasodilatory effect of CO2; the Bohr effect or the increase in the dissociation of oxygen from hemoglobin in the presence of carbon dioxide.

[0015] CO2 injection provides multiple benefits: oxygenation, improvement of microcirculation, stimulation of collagen, anti-inflammatory properties. The clinically observed cosmetic benefits are the improvement of pigmentation of the circle under the eyes, the lightening of the eye contour.

[0016] Injected into the skin layers, the gas acts advantageously on the physical, mechanical and / or optical characteristics of the skin, in particular dark circles, both inside and outside, in particular on elasticity, volume flexibility, tone, firmness, luminosity, radiance, but also on the appearance of the surface of the skin, by improving its softness, relief, radiance and / or color.

[0017] Document WO2014142970 discloses a method and apparatus for applying carboxytherapy to a person. The method comprises the steps of: contacting a target body surface of the subject with a treatment device comprising a plurality of hollow needles attached to a contact surface of a housing and a source of CO2 in fluid communication with at least one of the plurality of hollow needles; applying pressure to the housing such that one or more of the plurality of hollow needles penetrate an epidermis or an outer layer of cells in the target body surface; applying a therapeutic amount of CO2 to the subject via said plurality of hollow needles; and removing the plurality of hollow needles from said target body surface.

[0018] According to this document, in certain embodiments, the needles have a length of approximately 0.1 mm, 0.15 mm, 0.2 mm, 0.3 mm, 0.4 mm, 0.5 mm, 0.6 mm, 0.7 mm, 0.8 mm, 0.9 mm, 1.0 mm, 1.5 mm, 2.0 mm, 2.5 mm, 3.0 mm, 3.5 mm, 4.0 mm, 4.5 mm, 5.0 mm, 6.0 mm, 7.0 mm, 8.0 mm, 9.0 mm or 10.0 mm. It is also stated that needle lengths can control depth levels and, therefore, the exact location where the treatment fluid will be administered.

[0019] There is a need to improve known devices for injecting gas under the skin, particularly carboxytherapy, to specifically target shallow gas delivery (no dermal or hypodermic delivery).

[0020] There is a need to improve known devices for injecting gas under the skin, in particular carboxytherapy, to improve the injection procedure and thus their effectiveness in obtaining more visible skin rejuvenation results in the injection area.

[0021] There is a need to improve known devices for injecting gas under the skin, particularly carboxytherapy, to reduce side effects such as significant swelling around the injection point, frequently encountered during treatments aimed at reducing the size of wrinkles and lightening dark circles.

[0022] There is a need to provide a device for better targeting and delivering gas to the skin layers, particularly in the dark circle region.

[0023] There is a need to provide a device for injecting gas under the skin to better correct, soften and / or erase the signs of skin aging and fatigue, such as dark circles, wrinkles, skin folds, in particular facial folds, or pigmentation.

[0024] There is a need to provide a device for injecting gas under the skin to better fill certain scars, for example due to acne.

[0025] There is a need to provide a device for subcutaneous gas injection that is safer than existing devices, particularly by reducing the amount of contaminated injected gas and / or including residual air stagnating in the microneedle prior to injection. Definition of invention

[0026] The invention relates to a device, in particular a cosmetic device, for the subcutaneous injection of gas, in particular carbon dioxide (CO2), comprising a gas reservoir in fluid communication with a hollow microneedle via a distribution line, it comprises a purge system for evacuating residual gases present in the microneedle.

[0027] The use of the device of the invention offers a lasting solution for the correction of the signs and disorders of skin aging, by improving the skin penetration of possible filling agents.

[0028] With hollow microneedles, the composition is delivered deeper to inside the skin, bypassing the SC layer.

[0029] Indeed, thanks to the choice of the dimensions of the needle, the injection is made easier.

[0030] The invention also relates to a method for subcutaneous injection of gas, in particular carbon dioxide (CO2), comprising (i) the implementation of a device as defined previously and (ii) the injection of the gas for a duration of between 1 second and 15 seconds with a flow rate of between 20 ml / min and 60 ml / min, in particular for an eye area, a crow's feet area and a glabella area.

[0031] The invention also relates to a kit comprising a device, in particular a cosmetic device, (100) for the subcutaneous injection of gas as defined above and a set of replacement microneedles.

[0032] Residual gases

[0033] According to the invention, the term "residual gases present in the micro-needle" means gases present in the micro-needle and in the fluid connections before the injection is carried out, for example air, any gases present in the micro-needle and originating, for example, from volatile components contained in the micro-needle or from contamination of the micro-needle by the external environment or by a user.

[0034] Basically, since the device is open, it is in contact with air which can enter and remain in the channel connected to the micro-needle. Air can have adverse effects on the injection if there is contamination. In addition, air can bias the actual quantity of gas to be injected.

[0035] Micro-needles

[0036] Hollow microneedles are described in many publications such as in the articles "Microneedles for transdermal drug delivery Advanced Drug Delivery Reviews, Volume 56, Issue 5, 27 March 2004, Pages 581-587, "Biodegradable polymer microneedles: Fabrication, mechanics and transdermal drug delivery", Journal of Controlled Release, Volume 104, Issue 1, 5 May 2005, Pages 51-66, "Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: fabrication methods and transport studies, transport studies", Devin V.McAllister et al, PNAS of November 25, 2003, 100 (24) 13755- 13760, “Hollow microneedle arrays with sharp beveled tip fabricated by LIGA and 3D soft lithography with polyvinyl alcohol”, F Perennes et al, published January 25, 2006, IOP Publishing Ltd Journal of Micromechanisy and Microengineering, Volume 16, Number 3, “Microneedle array for transdermal Chemical extraction and in situ analysis”, EVMukerjeeab et al, Sensors and Actuators A: Physical, Volume 114, Issues 2-3, 1 September 2004, Pages 267-275, or “Hollow Microneedle Arrays for . Intradermal Drug Delivery and DNA Electroporation,” Lievin Daugimont et al., The Journal of Membrane Biology, July 2010, Volume 236, Issue 1, pp. 117-125.

[0037] According to the invention, the hollow microneedles comprise at least one internal channel. Such a channel may be longitudinal, i.e. extending along a longitudinal axis of the microneedles, from their free ends to the base of the device, or transverse, i.e. extending along an axis extending obliquely or perpendicularly to the longitudinal axis of the microneedles. Preferably, the channel is longitudinal.

[0038] The microneedles may have a plurality of channels, longitudinal and / or transverse.

[0039] The microneedles may have a circular hollow internal cross-section.

[0040] Alternatively, the microneedles have a hollow internal section of other shapes, for example square, rectangular or triangular.

[0041] The length of a microneedle is measured, along its axis of elongation, from its free end to the point where it connects to the base forming the proximal end.

[0042] By way of illustration, the microneedles described in documents EP 2,594,313 or US 8,236,368 can be used according to the invention.

[0043] The channels passing through the microneedles may be continuous or discontinuous. Preferably, they are continuous.

[0044] The expression “axis of elongation of a micro-needle” designates an axis passing through the barycenters of the cross-sections of the micro-needle.

[0045] The expression “axis of elongation of a micro-needle” designates an axis passing through the barycenters of the cross-sections of the micro-needle.

[0046] Each microneedle may comprise a stop configured to limit the injection depth of the microneedle into the skin to less than or equal to 250 micrometers, better still 100 micrometers, and even better still 50 micrometers.

[0047] A larger internal transverse dimension of each microneedle, i.e. its diameter when the microneedle has a circular hollow section, may be less than or equal to 100 micrometers, better still 60 micrometers, even better still 30 micrometers.

[0048] The largest internal transverse dimension of the microneedles can be chosen according to the desired volume of composition to be dispensed.

[0049] The microneedles are preferably longer than the desired injection depth.

[0050] The length of the microneedles can be chosen according to the targeted skin layer in which the composition is to be delivered, obtaining the appropriate depth. proper in the skin.

[0051] The microneedles may be made of an inorganic material, preferably silicon, titanium, cobalt, ceramic, polyethylene or any material that can be implanted in the skin and / or the body, and more preferably still stainless steel.

[0052] Advantageously, the micro-needles have a fixing force to their support (tip) greater than or equal to 5N, better still 30N, even better still 50N.

[0053] The microneedles are preferably sterile or sterilized before use.

[0054] The microneedles are preferably single-use.

[0055] Preferably, the microneedles are non-absorbable.

[0056] By "non-absorbable microneedles" it is meant that the microneedles do not dissolve or degrade in vivo, and must be removed from the skin.

[0057] Cosmetic treatment process

[0058] The injection depth of the microneedle into the skin is preferably less than or equal to 250 micrometers, better still 100 micrometers, even better still 50 micrometers.

[0059] This depth range corresponds to the area above the dermo-epidermal junction, and prevents bleeding and pain and thus provides comfortable use of the device.

[0060] Device according to the invention

[0061] The device may cause the microneedles to puncture the skin at a deep level and then dispense the composition before removing the device or while removing the device.

[0062] This allows for a good distribution of the composition in the different layers of the skin.

[0063] The device may be connected by wireless communication to an electronic system, in particular a personal computer or a smartphone, for injection control.

[0064] An injection of CO2 gas increases blood flow in the skin, which increases oxygenation of the skin to reduce the intensity of dark circles.

[0065] Alternatively, the device comprises an electronic system.

[0066] Evaluation of skin changes

[0067] Methods for assessing skin changes may be used, such as optical coherence tomography (OCT), confocal microscopy, electron microscopy, quantitative and qualitative assessment methods.

[0068] The OCT method can be used to monitor and locate injection sites in the skin.

[0069] The OCT method can be useful to track the volume of gas filled inside skin, scalp or lips. Preferred embodiments

[0070] Preferably, the device according to the invention has one or more of the following characteristics, taken alone or in combination:

[0071] The purge system is arranged upstream of the microneedle.

[0072] The purge system is arranged downstream of the distribution line.

[0073] The distribution line includes a pressure regulator.

[0074] The distribution line includes an upstream pipe for connecting the regulator pressure switch and a downstream line connecting the control switch to the microneedle.

[0075] The purge system has a main body including a valve.

[0076] The purge system has a two-stage switching mechanism.

[0077] The switching mechanism comprises an actuating button movable in the main body along a longitudinal axis (A), between a rest position in which the valve is closed and a first engagement position in which the valve is open and allows gas to pass towards the micro-needle at a first flow rate, to evacuate before injection, any residual gases stagnating in the micro-needle.

[0078] The actuating button cooperates with the valve via a first elastic element of first stiffness (ki), to allow the gas to pass towards the microneedle at the first flow rate and the first elastic element is in a first state of compression when the actuating button is in its first engagement position.

[0079] The actuating button is movable in the main body along a longitudinal axis (A), between the first engagement position and a second engagement position in which the valve is open and allows gas to pass towards the microneedle at a second flow rate, to carry out the injection.

[0080] The actuating button cooperates with the valve via the first elastic element of first stiffness (ki) and a second elastic element of stiffness (k2), to allow the gas to pass towards the micro-needle at the second flow rate, the first elastic element and the second elastic element are together in a second state of compression when the actuating button is in its second engagement position.

[0081] The hollow microneedle comprises an internal channel of average internal transverse dimension (IDmoy) extending between a distal free end and a proximal end, the hollow injection microneedle having a length (L) less than or equal to 250 mm and greater than or equal to 70 mm and a ratio (IDmoy / L) between the average internal transverse dimension (IDmoy) of the channel and its length (L) of between 0.15 and 0.86. Description of figures

[0082] Other characteristics and advantages of the invention will emerge from reading the detailed description which follows, from non-limiting examples of implementation thereof, schematic and partial, and from examining the attached drawing, in which:

[0083] [Fig.l]

[0084] [Fig.l] represents a first embodiment of a device which can be used for implementing the method according to the invention comprising an ON / OFF button,

[0085] [Fig.2]

[0086] [Fig.2] represents a first purge system which can be used in a device according to the invention, in the rest position,

[0087] [Fig.3]

[0088] [Fig.3] shows the purge system of [Fig.2] in the first release position,

[0089] [Fig.4]

[0090] [Fig.4] shows the purge system of Figures 2 and 3 in the second release position,

[0091] [Fig.5]

[0092] [Fig.5] represents a second purge system which can be used in a device according to the invention,

[0093] [Fig.6]

[0094] [Fig.6] represents the operation of the second purge system of [Fig.5]: A in rest position, B in first release position, C in second release position,

[0095] [Fig.7]

[0096] [Fig.7] represents the purge system of figures 5 and 6 integrated in a device according to the invention, in the rest position,

[0097] [Fig. 8]

[0098] [Fig. 8] represents the purge system of figures 5 and 6 integrated in a device according to the invention in the first release position,

[0099] [Fig.9]

[0100] [Fig.9] represents the purge system of figures 5 and 6 integrated in a device according to the invention in the second release position,

[0101] [Fig. 10]

[0102] [Fig. 10] represents a visualization in optical coherence tomography of the CO2 gas injected according to the method according to the invention with microneedles of length equal to 70 pm, for ex vivo pig skin. We obtained images equivalents with microneedles of length equal to 150 pm and 250 pm,

[0103] [Fig. 11]

[0104] [Fig. 11] represents a visualization in optical coherence tomography of an area to be treated before injection of CO2, in ex vivo pig skin,

[0105] [Fig. 12]

[0106] [Fig. 12] represents a visualization in optical coherence tomography of the area of ​​[Fig.l 1] after injection of CO2 with a needle of total length equal to 70 pm, in ex vivo pig skin,

[0107] [Fig. 13]

[0108] [Fig. 13] shows a comparison table of the ease / difficulty of injection according to the needle length (Ln) and the ratio (IDmoy / Ln), for ex vivo pig skin,

[0109] [Fig. 14]

[0110] [Fig. 14] shows a photo of ex vivo pig skin injected at a flow rate of 80 cm3 / min, [YES] [Fig. 15]

[0112] [Fig. 15] shows a photograph of ex vivo pig skin injected at a flow rate of 30 cm3 / min,

[0113] The method according to the invention comprises the subcutaneous injection of gas, in particular carbon dioxide (CO2).

[0114] [Fig.l] illustrates a device 100 according to the invention intended to be brought into contact with the skin of a person to carry out a gas injection.

[0115] The skin is for example made up of the skin of the face, in particular the skin of the dark circles under the eyes.

[0116] For example, this involves treating the dark circle area to rejuvenate the person's look.

[0117] The device 100 comprises a handpiece 101 which carries a gas reservoir 10, in contact with a distribution line 20, and from which gas, in particular CO2, is emitted towards a microneedle 4. In the reservoir 10, the gas pressure is advantageously between 40 and 70 bars.

[0118] Under the effect of the injection, gas bubbles are generated under the skin, which prove effective in improving its appearance.

[0119] The device 1 can be powered by a generator not shown, which can be part of the handpiece or not, being for example present within a base station to which the handpiece is connected by a cable.

[0120] In the distribution line 20, downstream of the tank 10, a pressure regulator 21 can be arranged, downstream of which a control button 23 can be placed to release the gas by user control. The control button 23 can be actuated by the user between an “OFF” position in which the gas is stopped and does not reach the microneedle and an “ON” position in which the gas can reach the microneedle for injection. Typically, the control knob is in the “OFF” position between injections and in the “ON” position during injection or just before injection.

[0121] The pressure regulator 21 is optional if the pressure of the gas contained in the tank 10 is equal to the pressure of the gas desired to carry out the injection. In this case, the pressure regulator 21 can also be configured with a fixed pressure. It can be controlled by a control button 18.

[0122] If the pressure of the gas contained in the reservoir 10 is higher than the pressure of the gas desired to carry out the injection, the pressure regulator 21 is necessary to lower the pressure of the gas entering the microneedle 4 releasing the gas at regulated pressure.

[0123] The gas pressure is advantageously between 1.5 bar and 3 bar after passing through the pressure regulator 21.

[0124] The push button 23 can be connected to the pressure regulator 21 by a first flexible conduit forming an upstream connection conduit 80 and to the microneedle 4 by a second flexible conduit forming a downstream connection conduit 81.

[0125] Figures 2 to 4 show a purge system that can be implemented in a device according to the invention. In the carboxytherapy device according to the invention, this purge system is inserted in place of the push button 23 of [Fig.l].

[0126] The purge system at rest is illustrated in [Fig.2].

[0127] Before treatment, it is advantageous to purge the channel of the microneedle 4 to maximize performance and also to avoid contamination. This ensures that the desired volume of gas is actually injected for treatment since the residual air present in the microneedle 4 before injection is removed by the purge and replaced by the desired gas from the reservoir 4, such as CO2.

[0128] The purge system 22 comprises a main body 50 comprising an internal gas passage 53 comprising a gas inlet 51 through which the gas at a first pressure flow rate value enters the internal passage 53 via the upstream pipe 80 and a gas outlet 52 through which the gas at a second pressure flow rate value is extracted from the internal passage 53 via the downstream pipe 81.

[0129] The purge system 22 is also provided with a control push button 31 moving in translation along the longitudinal axis A by action of a user on this control button.

[0130] In [Fig.2], the purge system is shown in a “rest position”, in which the passage of gas from the upstream pipe 80 is blocked by the main body 50.

[0131] [Fig. 3] shows the purge system 22 in a first release position allowing CO2 gas to pass from the upstream pipe 80 to the downstream pipe 81 at a low flow rate, to replace the air contained in the microneedle. To move from the rest position to this first position, the push button 31 has been moved by the user by the distance di along the axis A, in order to release the gas at low pressure into the downstream connection pipe 81 and then into the microneedle 4, for example at a flow rate of 10 cmVmin. The push button can be held in the first release position by a stop, possibly associated with a ring-shaped seal 37.

[0132] [Fig. 4] shows the purge system 22 in the second release position to inject gas under the skin. The push button has been moved by the user by the distance d2 along the axis A, d2 being greater than d1, in order to release the high-pressure gas into the downstream connection pipe 81 and then into the microneedle 4, for example at a flow rate of 40 cmVmin. The push button can be held in the second release position by a stop, possibly associated with a ring-shaped seal 38.

[0133] In the example shown in Figures 2 to 4, the purge system 22 comprises a two-stage thrust system, including two springs 56, 66 capable of exerting a stress on the pressure adjustment member 31. Each spring 56, 66 has a spring length and a spring constant specific to it, the first spring 56 having a stiffness ki less than the stiffness k2 of the second spring 66.

[0134] When the purge system is in the rest position ([Fig.2]), the springs 56, 66 are both in their maximum relaxation position, possibly already constrained by the push button 31.

[0135] At the first thrust stage ([Fig.3]), when the push button 31 has been moved by the user by the distance di along the axis A, the resistance of the assembly formed by the first and second springs is defined by the resistance of the lowest spring, i.e. by the resistance of the first spring 56, so that a valve (not shown) allows a limited quantity of CO2 gas to pass towards the micro-needle. The first spring 56 is in an intermediate position between its rest position of [Fig.2] and its second position of [Fig.4].

[0136] At the second thrust stage ([Fig.4]), when the push button 31 has been moved by the user by the distance d2 along the axis A, the resistance of the assembly is defined by the sum of the resistances of the two springs and the valve allows gas to pass at full flow towards the micro-needle 4 to carry out the injection. In this second position, the first spring 56 and the second spring 66 are in a state of maximum stress.

[0137] According to one embodiment of the invention, gas expansion means are arranged in the passage 53 between the inlets 51 and outlet 52, and serve to operate the desired gas pressure reduction.

[0138] The expansion means comprise, for example, an expansion valve cooperating with a valve seat, the expansion valve being able to be pushed back from its seat by an elastic means.

[0139] [Fig.6] shows an example of a push button that can be used to control the purge system 22 according to the invention. The push button is formed of a base 72 connected to a PCB board, a push button 74 being supported above the base to actuate the purge system.

[0140] The push button structure was designed for two purposes:

[0141] To mitigate the error by touching or pressing the push button 74 incorrectly,

[0142] Also, to provide a clear feeling of pressure when the push button 74 is pressed.

[0143] In the structure, the rubber dome 70 plays the role of the first spring described in connection with Figures 2 to 4 - to absorb shocks and begin the downward action with low resistance. The internal spring 71, located in the rubber dome 70, resists more with higher resistance, and allows the passage of gas when the force exerted by the user is sufficient and exceeds a predetermined threshold.

[0144] According to an advantageous embodiment of the invention, the internal spring 72 housed in the dome 70 provides resistance to close the gas passage if there is no pressure on the dome 70, and it will allow a small volume of CO2 to circulate to purge the path when the user pushes down the dome 70. The internal spring 72 plays the role of the second helical spring described in connection with Figures 2 to 4, and this provides the resistance to perform the purge and allow the gas to pass from the downstream pipe 81 to the upstream pipe 82.

[0145] These dual-action mechanisms exist in mechanical keyboards. There are many variations of the two-step switching system that can be used in the purge system according to the invention.

[0146] Figures 7 to 9 illustrate the operation of the purge system described with reference to Figures 5 and 6, in a device according to the invention. In other words, the device shown in Figures 7 to 9 is identical to that shown in Figures 2 to 4, except that the purge system has been replaced by that described separately in Figures 5 and 6.

[0147] The purge system shown in [Fig.7] uses elastic elements each having their own elasticity, the materials composing these elastic elements being different and being associated, therefore, with an elasticity which is specific to it. In this embodiment, the elastic material of the outer dome 70 can be silicone, elastomer, rubber, sponge.

[0148] In [Fig.8], the dome 70 provides a small resistance to keep the switch in the closed position. It can be actuated by the small pressure by action of a user to perform a purge and emit gas, in particular CO2, into the channel 81. The gas mixes with the gaseous residues 101 initially present in the microneedle and gradually dilutes these gaseous residues to completely occupy the internal channel of the microneedle 4. The valve will be allowed to open at a certain level of gas pressure and the user will feel a slight resistance pressure with resistance coming from the internal spring 71.

[0149] In [Fig.9], the spring 71 absorbs the higher pressure by the change of shape, and the valve will be fully open for maximum gas delivery.

[0150] The invention is not limited to purge systems equipped with the dual-action mechanisms described above. On the contrary, the invention relates to all devices for the subcutaneous injection of gas provided with a micro-needle purge system, regardless of the structure of this system, to eliminate the gas initially present in the micro-needle and decontaminate it, without limiting its application by the specific structure of the embodiment.

[0151] Tests to evaluate the device according to the invention were carried out on pig skins ex vivo.

[0152] [Fig. 10] illustrates the penetration and distribution of CO2 under the skin, after injection with a device according to the invention, under the following conditions:

[0153] Microneedle length: 70pm

[0154] CO2 flow rate: 30 cm3 / min

[0155] Injection duration: 10 s

[0156] The pig skin was prepared as follows: untreated, stored in the refrigerator at 5C overnight and used the next day as follows: excised with a scalpel at room temperature, the hairs were gently cut with surgical scissors so as to keep the skin intact.

[0157] It was placed on a cork sample holder and fixed with pins at the ends so as to stretch it.

[0158] The OCT equipment used is a Thorlabs Ganymede II.

[0159] Bubbles of CO2 having penetrated under the skin are observed, located between 100 and 300 µm deep. More bubbles are observed when the injected volume is larger. These bubbles disappear in a time of approximately 10 min.

[0160] It is estimated that CO2 gas could have been injected under the skin with needles of length 70 pm, 150 pm and 250 pm and with IDmoy / L ratios having values ​​of -—. For all these parameters, gas bubbles are observed under the skin distributed as shown in [Fig. 10].

[0161] In [Fig. 12], a histological section of the skin before CO2 injection has been mounted. and in [Fig. 11], a histological section of the skin immediately after CO2 injection typically under the injection conditions of [Fig. 10], with an injection time of 1 s. Bubbles are observed in the dermis. CO2 injection does not induce any apparent damage to the skin.

[0162] From the table shown in [Fig. 13], it can be deduced that:

[0163] a) Length of the micro-needle L:

[0164] Up to 150 pm in length, the microneedle is injected easily, without resistance, into the stratum corneum or the epidermis (so as not to reach the dermis). This specification is essential to achieve gas distribution at low skin depth.

[0165] A length of 70 pm has been found to be suitable for injecting CO2 into pig skin ex vivo. CO2 gas is successfully injected with microneedles of 70 pm, 150 pm and 250 pm (total length) into pig skin ex vivo.

[0166] b) IDmny / L ratio

[0167] This specification defines the success rate / ease of injection.

[0168] The IDmoy / L ratio is decisive for a correct injection: an easy injection has was obtained with ID / L < 0.2. Whereas ID / L = 0.86 led to very difficult injection into human skin ex-vivo.

[0169] [Fig. 14] shows a photograph of ex vivo pig skin immediately after treatment with the device according to the invention under the following conditions:

[0170] Microneedle length: 70 pm

[0171] CO2 flow rate: 80 cmVmin

[0172] Injection duration: 5 seconds

[0173] Significant swelling is observed around the injection point (shown by an arrow).

[0174] [Fig. 15] shows a photograph of ex vivo pig skin immediately after treatment with the device according to the invention under the following conditions:

[0175] Microneedle length: 70 pm

[0176] CO2 flow rate: 30 cmVmin

[0177] Injection duration: 5 s

[0178] A very slight swelling is observed in an area 36 around the injection point. By comparing the photographs in Figures 14 and 15, it is concluded that a flow rate of 30 cm3 / min allows satisfactory control of the dose of injected CO2, with a slight reversible swelling. A flow rate of 80 cm3 / min is too aggressive and leads to very significant swelling.

Claims

Claims

1. Device (100), in particular cosmetic, for the subcutaneous injection of gas, in particular carbon dioxide (CO2), comprising a gas reservoir (10) in fluid communication with a hollow microneedle (4) via a distribution line (20), characterized in that it comprises a purge system (22) for evacuating residual gases present in the microneedle.

2. Device (100), in particular cosmetic, according to claim 1, characterized in that the purge system (22) is arranged upstream of the microneedle (4).

3. Device (100), in particular cosmetic, according to any one of the preceding claims, characterized in that the purge system (22) is arranged downstream of the distribution line (20).

4. Device (100), in particular cosmetic, according to any one of the preceding claims, characterized in that the distribution line (20) comprises a pressure regulator (21).

5. Device (100), in particular cosmetic, according to any one of the preceding claims, characterized in that the distribution line (20) comprises an upstream pipe (80) for connecting the pressure regulator (21) to the control switch (23) and a downstream pipe (81) for connecting the control switch (23) to the microneedle (4).

6. Device (100), in particular cosmetic, according to the preceding claim, characterized in that the purge system (22) is provided with a main body (50) including a valve.

7. Device (100), in particular cosmetic, according to any one of the preceding claims, characterized in that the purge system (22) comprises a two-step switching mechanism.

8. Device (100), in particular cosmetic, according to the preceding claim, characterized in that the switching mechanism comprises an actuating button (31) movable in the main body (50) along a longitudinal axis (A), between a rest position in which the valve is closed and a first engagement position in which the valve is open and allows gas to pass towards the micro-needle (4) at a first flow rate, to evacuate before injection, the (possible) residual gases stagnating in the micro-needle.

9. Device (100), in particular cosmetic, according to claim previous, characterized in that the actuating button (31) cooperates with the valve via a first elastic element (56) of first stiffness (ki), to allow the gas to pass towards the microneedle (4) at the first flow rate and the first elastic element (56) is in a first state of compression when the actuating button (31) is in its first engagement position.

10. Device (100), in particular cosmetic, according to any one of claims 8 or 9, characterized in that the actuating button (31) is movable in the main body (50) along a longitudinal axis (A), between the first engagement position and a second engagement position in which the valve is open and allows the gas to pass towards the micro-needle (4) at a second flow rate, to carry out the injection.

11. Device, in particular cosmetic, according to any one of claims 8 to 10, characterized in that the actuating button (31) cooperates with the valve via the first elastic element (56, 70) of first stiffness (ki) and a second elastic element of stiffness (k2), to allow the gas to pass towards the micro-needle (4) at the second flow rate, the first elastic element (56, 70) and the second elastic element (66, 71) are together in a second state of compression when the actuating button (31) is in its second engagement position.

12. Device (100), in particular cosmetic, according to any one of the preceding claims, characterized in that the hollow microneedle (4) comprises an internal channel of average internal transverse dimension (IDmoy) extending between a distal free end and a proximal end, the hollow injection microneedle (4) having a length (L) less than or equal to 250 pm and greater than or equal to 70 pm and a ratio (IDmoy / L) between the average internal transverse dimension (IDmoy) of the channel and its length (L) of between 0.15 and 0.

86.

13. Kit comprising a device, in particular a cosmetic device, (100) for the subcutaneous injection of gas as defined according to any one of claims 1 to 12 and a set of replacement microneedles (4).

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