EP4688084A1

EP4688084A1 - Carboxytherapy device with hollow microneedle

Info

Publication number: EP4688084A1
Application number: EP24714178.1A
Authority: EP
Inventors: Woo Ram Park; Charlotte PELLET
Original assignee: LOreal SA
Current assignee: LOreal SA
Priority date: 2023-04-07
Filing date: 2024-03-22
Publication date: 2026-02-11

Abstract

The invention relates to a device (100), in particular a cosmetic device, 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). It comprises a purge system (22) for evacuating residual gases present in the microneedle.

Description

Title: CARBOXYTHERAPY DEVICE WITH HOLLOW MICRONEEDLE

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

[0002] The gases that can be injected according to the invention are chosen in particular 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 30 November 2009, relating to cosmetic products.

Technological background

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

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

[0006] The facial muscles then work closer to the surface of the skin, so that smile wrinkles 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) is the main barrier of the epidermis to exogenous substances, including the low and high weight molecular biopolymer compositions used as cosmetic fillers.

[0010] Techniques aimed at removing the SC barrier, such as stripping and aspiration, laser or thermal ablation, are impractical, while needleless injections have so far failed to replace known needle-based administration. Such a mode of delivery may be uncomfortable, or even painful, because of the shape of the needles and the viscosity of the composition, like compositions comprising hyaluronic acid, and it is therefore unpleasant for users.

[0011] Dark circles are a feature of the expression that are frequently found in the population. The appearance of dark circles, aggravated by physiological ageing of the face, affects men and women of all ages and is often an important aesthetic concern on account of the tired expression they bring to the eyes.

[0012] Thin cutaneous tissue is most probably the main reason for darker skin around the eyes. This fine skin reveals the underlying veins and capillaries, giving the area a bluish, even purplish, or greyish colour. This colouring is aggravated in cases of vascular congestion and lack of oxygenation in the periorbital zone. 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 common cause is excessive pigmentation of the skin, whether spontaneous or induced by the environment.

[0013] The challenge lies in achieving overall management of dark circles, including improving the skin colouration, for which injections (of hyaluronic acid for example) alone have not demonstrated efficacy. Laser treatment and chemical peels exist but are generally very aggressive and accompanied by significant adverse effects.

[0014] Carboxytherapy involves subcutaneous injection of carbon dioxide (CO2), very often targeting the dermis or hypodermis. The injected CO2 creates hypercapnic stress, which increases transcutaneous oxygen pressure (tc-PCh) through three phenomena: an increase in capillary blood flow; a reduction in cutaneous oxygen consumption caused by the vasodilator effect of CO2; the Bohr effect, or the increased dissociation of oxygen from haemoglobin in the presence of carbon dioxide.

[0015] Injection of CO2 affords many benefits: oxygenation, improvement of the microcirculation, collagen stimulation, anti-inflammatory properties. The cosmetic advantages observed clinically are the improvement in the pigmentation of the rings under the eyes, and the brightening of the eye contour.

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

[0017] The document WO2014142970 discloses a method and an apparatus for applying carb oxy therapy to a person. The method includes the steps of: bringing a target body surface of the subject into contact with a treatment device comprising a plurality of hollow needles attached to a contact surface of a housing, and a CO2 source in fluidic 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 through said plurality of hollow needles; and removing the plurality of hollow needles from the target body surface.

[0018] According to said 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 the needle lengths can control the depth levels and therefore the exact location where the treatment fluid will be administered.

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

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

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

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

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

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

[0025] There is a need to provide a device for subcutaneous gas injection that is safer than existing devices, in particular by reducing the amount of injected gas contaminated and/or containing residual air stagnant in the microneedle prior to the injection. Definition of the 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 fluidic 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 according to the invention offers a lasting solution for correcting signs and disorders of skin ageing, by improving the cutaneous penetration of possible fillers.

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

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

[0030] The invention also relates to a method for subcutaneous injection of gas, in particular carbon dioxide (CO2), comprising (i) the use of a device as defined above, and (ii) the injection of the gas for a period 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 region, a crow’ s foot region and a glabella region.

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

[0032] Residual gases

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

[0034] Basically, since the device is open, it is in contact with air that can enter and remain in the channel connected to the microneedle. Air can have a detrimental effect on the injection if there is contamination. In addition, the air can bias the actual quantity of gas to be injected.

[0035] Microneedles

[0036] Hollow microneedles are described in numerous 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, mechanism and transdermal drug delivery”, Journal of Controlled Release, volume 104, number 1, 5 May 2005, pages 51-66, “Microfabricated needles for transdermal administration of macromolecules and nanoparticles: manufacturing methods and transport studies, transport studies”, Devin V. McAllister et al., PNAS of 25 November 2003, 100 (24) 13755-13760, “Hollow microneedle matrices with bevelled tip manufactured by Liga and 3D soft lithography with polyvinyl alcohol”, F Perennes et al., published 25 January 2006, IOP Publishing Ltd Journal of Micromechanics and Microengineering, volume 16, number 3, “Microneedle array for transdermal chemical extraction and in situ analysis”, E. V. Mukerjeeab et al., Sensors and Actuators A: Physical, volume 114, issues 2-3, 1 September 2004, pages 267-275, or “Hollow Microneedle Arrays for the intradermal administration of drugs and the electroporation of DNA”, Lievin Daugimont et al., The Journal of Membrane Biology, July 2010, volume 236, number 1, pp 117-125.

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

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

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

[0040] In a variant, 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 the 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 microneedle" designates an axis passing through the barycentres of the transverse sections of the microneedle. [0045] Each microneedle can comprise a stop configured to limit the depth of injection of the microneedle into the skin to less than or equal to 250 micrometres, preferably to 100 micrometres, more preferably to 50 micrometres.

[0046] A larger internal transverse dimension of each microneedle, that is to say its diameter when the microneedle has a circular hollow section, may be less than or equal to 100 micrometres, preferably less than or equal to 60 micrometres, more preferably less than or equal to 30 micrometres.

[0047] The largest internal transverse dimension of the microneedles can be chosen as a function of the desired volume of composition to be dispensed.

[0048] The microneedles are preferably longer than the desired depth of injection.

[0049] The length of the microneedles can be chosen as a function of the targeted skin layer into which the composition is to be delivered, obtaining the appropriate depth in the skin.

[0050] Microneedles may be made of an inorganic material, preferably silicon, titanium, cobalt, ceramic, polyethylene or any material implantable in the skin and/or the body, and still more preferably stainless steel.

[0051] Advantageously, the microneedles have a force of attachment to their support (endpiece) greater than or equal to 5N, preferably greater than or equal to 3 ON, more preferably greater than or equal to 50N.

[0052] The microneedles are preferably sterile or sterilized prior to use.

[0053] The microneedles are preferably disposable.

[0054] Preferably, the microneedles are non-absorbable.

[0055] The term “ non-absorbable microneedles” is to be understood as meaning that the microneedles do not dissolve or degrade in vivo, and that they have to be removed from the skin.

[0056] Cosmetic treatment process

[0057] The depth of injection of the microneedle into the skin is preferably less than or equal to 250 micrometres, preferably less than or equal to 100 micrometres, more preferably less than or equal to 50 micrometres.

[0058] This range of depths corresponds to the area above the dermo-epidermal junction and prevents bleeding and pain and thus offers comfortable use of the device. [0059] Device according to the invention

[0060] The device may cause the microneedles to perforate the skin to a deep level and then dispense the composition prior to removal of the device or indeed during removal of the device.

[0061] This makes it possible to obtain a good distribution of the composition in the various layers of the skin.

[0062] The device may be wirelessly connected to an electronic system, notably a personal computer or a smartphone, for controlling the injection.

[0063] An injection of CO2 gas increases the blood flow in the skin, which can increase the oxygenation of the skin in order to decrease the intensity of dark circles.

[0064] Alternatively, the device comprises an electronic system.

[0065] Evaluation of skin changes

[0066] Methods for evaluating skin changes can be used, such as optical coherence tomography (OCT), confocal microscopy, electron microscopy, and quantitative and qualitative evaluation methods.

[0067] The OCT method can be used to monitor and locate the injection sites in the skin.

[0068] The OCT method can be useful for tracking the volume of gas filled inside the skin, scalp or lips.

Preferred embodiments

[0069] Preferably, the device according to the invention has one or more of the following features, taken alone or in combination:

[0070] The purge system is disposed upstream of the microneedle.

[0071] The purge system is disposed downstream of the distribution line.

[0072] The distribution line comprises a pressure regulator.

[0073] The distribution line comprises an upstream conduit for connecting the pressure regulator to a control switch and a downstream conduit for connecting the control switch to the microneedle.

[0074] The purge system is equipped with a main body including a valve.

[0075] The purge system comprises a two-stage switching mechanism. [0076] 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 the gas to pass to the microneedle at a first flow rate, in order to evacuate, before injection, any residual gases stagnant in the microneedle.

[0077] The actuating button cooperates with the valve via a first elastic element of first stiffness (ki), to allow the gas to pass to the microneedle at the first flow rate, and the first elastic element is in a first compression state when the actuating button is in its first engagement position.

[0078] 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 the gas to pass to the microneedle at a second flow rate, in order to effect the injection.

[0079] The actuating button cooperates with the valve via the first elastic element of first stiffness (ki) and a second elastic element of stiffness (k2), in order to allow the gas to pass to the microneedle at the second flow rate, the first elastic element and the second elastic element together being in a second compression state when the actuating button is in its second engagement position.

[0080] The hollow microneedle comprises an internal channel of mean internal transverse dimension (IDmean) extending between a distal free end and a proximal end, the hollow microneedle for injection having a length (L) of less than or equal to 250 pm and greater than or equal to 70 pm and a ratio (IDmean/L) of the mean internal transverse dimension (IDmean) of the channel to its length (L) of between 0.15 and 0.86.

[0081] 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 fluidic communication with a hollow microneedle via a distribution line, the hollow microneedle comprising an internal channel of mean internal transverse dimension (IDmean) extending between a distal free end and a proximal end, the hollow microneedle for injection having a length (L) of less than or equal to 250 mm and of greater than or equal to 70 mm, and the microneedle for injection having a ratio (IDmean/L) of the mean internal transverse dimension (IDmean) of the channel to its length (L) of between 0.15 and 0.86. [0082] The use of the device according to the invention offers a lasting solution for correcting signs and disorders of skin ageing, by improving the cutaneous penetration of possible fillers.

[0083] With hollow microneedles, the composition is delivered deeper into the skin, bypassing the SC layer.

[0084] Indeed, the injection is made easier thanks to the chosen needle dimensions.

[0085] The invention also relates to a method for subcutaneous injection of gas, in particular carbon dioxide (CO2), comprising (i) the use of a device as defined above, and (ii) the injection of the gas for a period 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 region, a crow’ s foot region and a glabella region.

[0086] Preferably, the microneedle is purged before the injection.

[0087] The invention also relates to a kit comprising a device, in particular a cosmetic device, for the subcutaneous injection of gas as defined above, and a batch of replacement microneedles.

Preferred embodiments

[0088] Preferably, the device according to the invention has one or more of the following features, taken alone or in combination:

[0089] The microneedle is configured to deliver the gas at a flow rate of less than 80 cm³/min, in particular at a flow rate of between 20 cm³/min and 60 cm³/min.

[0090] The distribution line comprises a pressure regulator.

[0091] The distribution line comprises a switch for controlling the distribution of gas to the microneedle.

[0092] The distribution line comprises an upstream conduit for connecting the pressure regulator to the control switch and a downstream conduit for connecting the control switch to the microneedle.

[0093] The distribution line comprises a purge system disposed upstream of the microneedle in order to evacuate, before an injection, residual gases stagnant in the microneedle.

[0094] The purge system is equipped with a main body including a valve.

[0095] The purge system comprises a two-stage switching mechanism. Description of the figures

[0096] Further features and advantages of the invention will become apparent from reading the following detailed description of non-limiting implementation examples thereof, schematic and partial, and from examining the appended drawing, in which:

[0097] [Fig. 1]

[0098] Figure 1 shows a first embodiment of a device that can be used for carrying out the method according to the invention, comprising an ON/OFF button,

[0099] [Fig. 2]

[00100] Figure 2 shows a first purge system that can be used in a device according to the invention, in a rest position,

[00101] [Fig. 3]

[00102] Figure 3 shows the purge system from Figure 2 in a first release position,

[00103] [Fig. 4]

[00104] Figure 4 shows the purge system from Figures 2 and 3 in a second release position,

[00105] [Fig. 5]

[00106] Figure 5 shows a second purge system that can be used in a device according to the invention,

[00107] [Fig. 6]

[00108] Figure 6 shows the operation of the second purge system from Figure 5: A in the rest position, B in the first release position, C in the second release position,

[00109] [Fig. 7]

[00110] Figure 7 shows the purge system from Figures 5 and 6 integrated into a device according to the invention, in the rest position,

[00111] [Fig. 8]

[00112] Figure 8 shows the purge system from Figures 5 and 6 integrated into a device according to the invention, in the first release position,

[00113] [Fig. 9] [00114] Figure 9 shows the purge system from Figures 5 and 6 integrated into a device according to the invention, in the second release position,

[00115] [Fig. 10]

[00116] Figure 10 shows a visualization, by optical coherence tomography, of the CO2 gas injected by the method according to the invention with microneedles of length equal to 70 pm, for ex-vivo porcine skin. We obtained equivalent images with microneedles of length equal to 150 pm and 250 pm,

[00117] [Fig. 11]

[00118] Figure 11 shows a visualization, by optical coherence tomography, of a treatment region before injection of CO2, into ex-vivo porcine skin,

[00119] [Fig. 12]

[00120] Figure 12 shows a visualization, by optical coherence tomography, of the region from Figure 11 after injection of CO2 with a needle of total length equal to 70 pm, into ex-vivo porcine skin,

[00121] [Fig. 13]

[00122] Figure 13 shows a comparison table of the ease/difficulty of injection according to the needle length (Ln) and the ratio (IDmean/Ln), for ex-vivo porcine skin,

[00123] [Fig. 14]

[00124] Figure 14 shows a photo of ex-vivo porcine skin injected into at a rate of 80 cm³/min,

[00125] [Fig. 15]

[00126] Figure 15 shows a photo of ex-vivo porcine skin injected into at a rate of 30 cm³/min.

[00127] The method according to the invention involves the subcutaneous injection of gas, in particular carbon dioxide (CO2).

[00128] Figure 1 illustrates a device 100 according to the invention, intended to be brought into contact with the skin of a person in order to inject gas.

[00129] The skin is constituted, for example, of the facial skin, in particular the skin of the dark circles under the eyes.

[00130] For example, the treatment involves treating region of the dark circles in order to rejuvenate the person’s expression. [00131] 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 pressure of the gas is advantageously between 40 and 70 bar.

[00132] Under the effect of the injection, gas bubbles are generated under the skin, which prove effective in improving the appearance of the skin.

[00133] The device 1 can be powered by a generator (not shown), which may or may not be part of the handpiece, for example being present within a base station to which the handpiece is connected by a cable.

[00134] In the distribution line 20, downstream of the reservoir 10, a pressure regulator 21 can be disposed, downstream of which a control button 23 can be placed for releasing the gas on command by the user. 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. As a general rule, the control button is in the “OFF” position between two injections and in the “ON” position during the injection or just before the injection.

[00135] The pressure regulator 21 is optional if the pressure of the gas contained in the reservoir 10 is equal to the desired pressure of the gas for carrying 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.

[00136] If the pressure of the gas contained in the reservoir 10 is greater than the desired pressure of the gas for carrying out the injection, the pressure regulator 21 is necessary for lowering the pressure of the gas entering the microneedle 4 so as to release the gas at regulated pressure.

[00137] The pressure of the gas is advantageously between 1.5 bar and 3 bar after it has passed through the pressure regulator 21.

[00138] 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. [00139] Figures 2 to 4 show a purge system that can be used 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 Figure 1.

[00140] Figure 2 illustrates the purge system at rest.

[00141] Before treatment, it is advantageous to purge the channel of the microneedle 4 in order to maximize performance and also to avoid contamination. It is thus ensured that the desired volume of gas is effectively injected for the treatment, since the residual air present in the microneedle 4 before injection is eliminated by the purge and replaced by the desired gas coming from the reservoir 10, such as CO2.

[00142] The purge system 22 comprises a main body 50 comprising an internal gas passage 53 having a gas inlet 51, through which the gas at a first pressure flow rate value enters the internal passage 53 via the upstream conduit 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 conduit 81.

[00143] The purge system 22 is also equipped with a control push-button 31 which moves in translation along the longitudinal axis A under the action performed by a user on this control button.

[00144] In Figure 2, the purge system is shown in a “rest position”, in which the passage of the gas coming from the upstream conduit 80 is blocked by the main body 50.

[00145] Figure 3 shows the purge system 22 in a first release position allowing CO2 gas to pass from the upstream conduit 80 to the downstream conduit 81 at a low flow rate, in order to replace the air contained in the microneedle. To go 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 conduit 81 and then into the microneedle 4, for example at a flow rate of 10 cm³/min. The push-button can be held in the first release position by a stop, optionally associated with a ring-shaped seal 37.

[00146] Figure 4 shows the purge system 22 in the second release position for injecting gas under the skin. The push-button has been moved by the user by the distance d2 along the axis A, d2being greater than di, in order to release the gas at high pressure into the downstream connection conduit 81 and then into the microneedle 4, for example at a flow rate of 40 cm³/min. The push-button can be held in the second release position by a stop, optionally associated with a ring-shaped seal 38. [00147] In the example shown in Figures 2 to 4, the purge system 22 comprises a two-stage push system, including two springs 56, 66 capable of exerting a stress on the pressure-adjusting member 31. Each spring 56, 66 has a spring length and a spring constant that is specific to it, the first spring 56 having a stiffness ki less than the stiffness k2 of the second spring 66.

[00148] When the purge system is in the rest position (Figure 2), the springs 56, 66 are both in their maximum release position, possibly already stressed by the push-button 31.

[00149] In the first push stage (Figure 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 weaker spring, that is to say 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 microneedle. The first spring 56 is in an intermediate position between its rest position in Figure 2 and its second position in Figure 4.

[00150] At the second push stage (Figure 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 rate towards the microneedle 4 in order 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.

[00151] According to one embodiment of the invention, gas expansion means are arranged in the passage 53 between the inlet 51 and outlet 52 and serve to effect the desired gas pressure reduction.

[00152] The expansion means comprise, by way of 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.

[00153] Figure 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 by a base 72 connected to a PCB, a push-button pad 74 being supported above the base to actuate the purge system.

[00154] The push-button structure has been designed for two purposes:

[00155] To mitigate the error caused by touching or pressing the push-button pad 74 incorrectly,

[00156] Also, to provide a clear sense of pressing when the push-button pad 74 is depressed. [00157] In the structure, the rubber dome 70 plays the role of the first spring described with reference to Figures 2 to 4, i.e. to absorb shocks and to begin the downward action with low resistance. The internal spring 71, located within the rubber dome 70, resists further with a higher resistance and allows gas to pass through when the force exerted by the user is sufficient and exceeds a predetermined threshold.

[00158] According to an advantageous embodiment of the invention, the internal spring 71 housed within the dome 70 provides a resistance to close the gas passage if there is no pressure on the dome 70, and it will make it possible to circulate a small volume of CO2 in order to purge the path when the user depresses the dome 70. The internal spring 71 plays the role of the second helical spring described in connection with Figures 2 to 4, and this provides the resistance for purging and for allowing the gas to pass from the downstream conduit 81 to the upstream conduit 82.

[00159] These twin-action mechanisms exist in mechanical keyboards. There are many variants of the two-stage switching system that can be used in the purge system according to the invention.

[00160] 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 the one described in isolation in Figures 5 and 6.

[00161] The purge system shown in Figure 7 uses elastic elements that each have their own elasticity, the constituent materials of these elastic elements being different and therefore being associated with an elasticity specific to them. In this embodiment, the elastic material of the outer dome 70 can be silicone, elastomer, rubber or sponge.

[00162] In Figure 8, the dome 70 provides a small resistance in order to hold the switch in the closed position. It can be actuated by the small pressure applied by the action of a user in order to carry out a purge and to emit into the channel 81 gas, in particular CO2. The gas mixes with the gaseous residues 101 initially present in the microneedle and progressively dilutes these gaseous residues so as to occupy entirely 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 a resistance coming from the internal spring 71.

[00163] In Figure 9, the spring 71 absorbs the higher pressure by the change of shape, and the valve will be fully opened for maximum gas delivery. [00164] The invention is not limited to purge systems equipped with the twin-action mechanisms described above. On the contrary, the invention relates to all devices for subcutaneous injection of gas that are equipped with a microneedle purge system, regardless of the structure of this system, in order to remove the gas initially present in the microneedle and decontaminate the latter, without limiting its application by the specific structure of the embodiment.

[00165] Tests to evaluate the device according to the invention were carried out on ex-vivo porcine skins.

[00166] Figure 10 illustrates the penetration and distribution of CO2 under the skin, after injection with a device according to the invention, under the following conditions:

[00167] Microneedle length: 70 pm

[00168] CO2 flow rate: 30 cm³/min

[00169] Duration of injection: 10 seconds

[00170] The porcine skin was prepared as follows: Untreated, stored in a refrigerator at 5°C overnight and used the next day as follows: Excised with a scalpel at room temperature, the hairs were cut gently with surgical scissors so as to keep the skin intact.

[00171] It was placed on a cork sample holder and fixed with pins at the ends in order to tension it.

[00172] The OCT equipment used is a Ganymede II Thorlabs.

[00173] Bubbles of CO2 that have penetrated under the skin are observed, located at a depth of between 100 and 300 pm. More bubbles are observed when the injected volume is larger. These bubbles disappear within about 10 minutes.

[00174] It is estimated that the CO2 gas was able to be injected under the skin with needles of length 70 pm, 150 pm and 250 pm and with IDmean/L ratios having values of — . For all these parameters, gas bubbles are observed under the skin that are distributed as shown in Figure 10.

[00175] Figure 12 shows a histological section of the skin before CO2 injection, and Figure 11 shows a histological section of the skin immediately after CO2 injection, typically under the injection conditions of Figure 10, with an injection time of 1 second. Bubbles are observed in the dermis. The injection of CO2 does not cause any apparent skin damage.

[00176] From the table shown in Figure 13, it can be deduced that: [00177] a) Microneedle length L:

[00178] Up to a length of 150 pm, the microneedle is injected easily, without resistance, into the stratum corneum or epidermis (so as not to reach the dermis). This specification is essential for achieving a gas distribution at a shallow depth of the skin.

[00179] A length of 70 pm has proven appropriate for injecting CO2 into ex-vivo porcine skin. The CO2 gas is successfully injected with microneedles of 70 pm, 150 pm and 250 pm (total length) into ex-vivo porcine skin.

[00180] b) IDmean/L ratio

[00181] This specification defines the success rate / ease of injection.

[00182] The IDmean/L ratio is decisive for correct injection: easy injection was obtained with ID/L < 0.2. Whilst ID/L = 0.86 led to a very difficult injection into ex-vivo human skin.

[00183] Figure 14 shows a photograph of ex-vivo porcine skin immediately after treatment by the device according to the invention, under the following conditions:

[00184] Microneedle length: 70 pm

[00185] CO2 flow rate: 80 cm³/min

[00186] Duration of injection: 5 seconds

[00187] Considerable swelling is observed around the injection site (indicated by an arrow).

[00188] Figure 15 shows a photograph of ex-vivo porcine skin immediately after treatment by the device according to the invention, under the following conditions:

[00189] Microneedle length: 70 pm

[00190] CO2 flow rate: 30 cm³/min

[00191] Duration of injection: 5 seconds

[00192] A very slight swelling is observed in a zone 36 around the injection site. Comparing the photographs in Figures 14 and 15, it is concluded that a flow rate of 30 cm³/min allows satisfactory control of the injected CO2 dose, with slight and reversible swelling. A flow rate of 80 cm³/min is too aggressive and leads to very considerable swelling.

Claims

[Claim 1] Device (100), in particular a cosmetic device, 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), characterized in that it comprises a purge system (22) for evacuating residual gases present in the microneedle.

[Claim 2] Device (100), in particular a cosmetic device, according to Claim 1, characterized in that the purge system (22) is disposed upstream of the microneedle (4).

[Claim 3] Device (100), in particular a cosmetic device, according to either of the preceding claims, characterized in that the purge system (22) is disposed downstream of the distribution line (20).

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

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

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

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

[Claim 8] Device (100), in particular a cosmetic device, 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 the gas to pass to the microneedle (4) at a first flow rate, in order to evacuate, before injection, any residual gases stagnant in the microneedle.

[Claim 9] Device (100), in particular a cosmetic device, according to the preceding claim, 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 to the microneedle (4) at the first flow rate, and the first elastic element (56) is in a first compression state when the actuating button (31) is in its first engagement position.

[Claim 10]Device (100), in particular a cosmetic device, according to either of Claims 8 and 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 to the microneedle (4) at a second flow rate, in order to effect the injection.

[Claim 1 l]Device, in particular a cosmetic device, 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), in order to allow the gas to pass to the microneedle (4) at the second flow rate, the first elastic element (56, 70) and the second elastic element (66, 71) together being in a second compression state when the actuating button (31) is in its second engagement position.

[Claim 12]Device (100), in particular a cosmetic device, according to any one of the preceding claims, characterized in that the hollow microneedle (4) comprises an internal channel of mean internal transverse dimension (IDmean) extending between a distal free end and a proximal end, the hollow microneedle (4) for injection having a length (L) of less than or equal to 250 pm and greater than or equal to 70 pm and a ratio (IDmean/L) of the mean internal transverse dimension (IDmean) of the channel to its length (L) of between 0.15 and 0.86.

[Claim 13] Method for subcutaneous injection of gas, in particular carbon dioxide (CO2), comprising (i) the use of a device according to any one of the preceding claims and (ii) the injection of the gas for a period 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 region, a crow’s foot region and a glabella region.

[Claim 14]Kit comprising a device (100), in particular a cosmetic device, for the subcutaneous injection of gas as defined according to any one of Claims 1 to 12, and a batch of replacement microneedles (4).