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) having an internal channel of mean internal transverse dimension (IDmoy), the hollow injection microneedle (4) having a length (L) less than or equal to 250 mm and greater than or equal to 70 mm. [Fig. 1]

Description

Title of the invention: CARBOXY THERAPY DEVICE WITH HOLLOW MICRO-NEEDLE

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

[0002] The gases that can be injected according to the invention are in particular chosen from among 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 of 30 November 2009 on 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 surface of the skin, so that smile lines and crow's feet, for example, become more apparent.

[0007] The skin of the face 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 Comeum (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 aimed at eliminating the subcutaneous barrier, such as stripping and aspiration, laser, or thermal ablation, are not practical, while needle-free injections have so far failed to replace the known needle-based administration method. 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 containing hyaluronic acid, and is therefore unaesthetic for users.

[0011] Dark circles are a common facial feature. The appearance of dark circles, exacerbated by the physiological aging of the face, affects men and women of all ages and is often a significant aesthetic concern due to the tired appearance they give to the eyes.

[0012] The thinness of the skin tissue is undoubtedly the main reason for the darker skin around the eyes. This thin skin allows the veins and capillaries to show through. Underlying factors give the area a bluish, even purplish, or grayish tint. This discoloration is exacerbated by vascular congestion and lack of oxygen in the periorbital area. Furthermore, as the skin ages, the lipid layer under the eyes sags and swells, creating shadows and thus making this area appear even darker. A second frequently observed cause is excessive skin pigmentation, whether spontaneous or induced by the environment

[0013] . The challenge lies in a comprehensive approach to dark circles, including improving skin pigmentation, for which injections (of hyaluronic acid, for example) alone have not proven effective. 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 transcutaneous oxygen pressure (tc-PO2) through 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 offers multiple benefits: increased oxygenation, improved microcirculation, collagen stimulation, and anti-inflammatory properties. Clinically observed cosmetic benefits include improved pigmentation of the under-eye area and brightening 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 of dark circles, both inside and outside, in particular on elasticity, volumetric suppleness, tone, firmness, luminosity, radiance, but also on the appearance of the skin surface, by improving its softness, relief, radiance and / or color.

[0017] A method and apparatus for administering carboxytherapy to a person is known from document WO2014142970. The method comprises 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 casing and a CO2 source in fluidic communication with at least one of the plurality of hollow needles; applying pressure to the casing so 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 quantity 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 specified 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 known devices for injecting gas under the skin, particularly carboxytherapy, to specifically target the administration of gas at shallow depths (not dermal or hypodermal administration).

[0020] There is a need to improve known devices for injecting gas under the skin, particularly carboxytherapy, to improve the injection technique and thus their effectiveness in obtaining more visible skin rejuvenation results on 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 to better target and deliver gas into the skin layers, particularly in the area of ​​dark circles.

[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, including 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, in particular by reducing the amount of gas injected that is contaminated and / or includes residual air stagnating in the micro-needle before injection. Definition of the invention

[0026] The invention relates to a device, particularly a cosmetic one, 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 having an internal channel of mean internal transverse dimension (IDmoy) extending between a distal free end and a proximal end, the hollow injection microneedle has a length (L) less than or equal to 250 mm and greater than or equal to 70 mm, the injection microneedle has a ratio (IDmoy / L) between the mean internal transverse dimension (IDmoy) of the channel and its length (L) of between 0.15 and 0.86.

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

[0028] With hollow micro-needles, the composition is delivered deeper inside the skin, bypassing the SC layer.

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

[0030] The invention also relates to a method of subcutaneous injection of gas, in particular carbon dioxide (CO2), comprising (i) the implementation of a device as defined above 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 area of ​​the eyes, an area of ​​the crow's feet and an area of ​​the glabella.

[0031] Preferably, the microneedle is primed before the injection is performed.

[0032] The invention also relates to a kit comprising a device, in particular cosmetic, for the subcutaneous injection of gas as defined above and a set of replacement microneedles.

[0033] Residual gases

[0034] According to the invention, "residual gases present in the microneedle" means gases present in the microneedle and in the fluidic fittings before the injection is carried out, for example air, possible gases present in the microneedle and originating, for example, from volatile components contained in the microneedle or from contamination of the microneedle by the external environment or by a user.

[0035] Fundamentally, since the device is open, it is in contact with air, which can enter and remain in the channel connected to the microneedle. Air can have adverse effects on the injection if there is contamination. Furthermore, air can skew the actual amount of gas injected.

[0036] Microneedles

[0037] Hollow microneedles are described in numerous publications such as 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 the transdermal delivery of macromolecules and nanoparticles: manufacturing methods and transport studies," Devin V. McAllister et al., PNAS, 25 November 2003, 100 (24) 13755-13760; and "Hollow microneedle matrices with a sharp beveled tip manufactured by LIGA and "3D soft lithography with polyvinyl alcohol", F Perennes et al, published on 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, September 1, 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, number 1, pp 117-125.

[0038] 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.

[0039] Microneedles can have a plurality of channels, longitudinal and / or transverse.

[0040] Microneedles may have a circular hollow internal cross-section.

[0041] Alternatively, the microneedles have a hollow internal section of other shapes, for example square, rectangular or triangular.

[0042] The length of a micro-needle is measured, along its elongation axis, from its free end to the point where it connects to the base forming the proximal end.

[0043] 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.

[0044] The channels passing through the microneedles can be continuous or discontinuous. Preferably, they are continuous.

[0045] The expression "axis of elongation of a microneedle" designates an axis passing through the barycenters of the cross sections of the microneedle.

[0046] The expression "axis of elongation of a micro-needle" designates an axis passing through the barycenters of the cross sections of the micro-needle.

[0047] Each microneedle may include a stop configured to limit the depth of injection of the microneedle into the skin to less than or equal to 250 micrometers, better to 100 micrometers, better still to 50 micrometers.

[0048] A larger internal transverse dimension of each microneedle, that is to say its diameter when the microneedle has a circular hollow section, can be less than or equal to 100 micrometers, better to 60 micrometers, even better to 30 micrometers.

[0049] The largest internal transverse dimension of the microneedles can be chosen in depending on the desired volume of composition to be distributed.

[0050] The microneedles are preferably longer than the desired injection depth.

[0051] The length of the microneedles can be chosen according to the targeted skin layer into which the composition is to be delivered, obtaining the appropriate depth in the skin.

[0052] The microneedles can be made of an inorganic material, preferably silicon, titanium, cobalt, ceramic, polyethylene or any material that can be implanted in the skin and / or body, and more preferably stainless steel.

[0053] Advantageously, the microneedles have a fixation force to their support (tip) greater than or equal to 5N, better at 30N, even better at 50N.

[0054] Microneedles are preferably sterile or sterilized before use.

[0055] Microneedles are preferably single-use.

[0056] Preferably, the microneedles are non-absorbable.

[0057] By "non-absorbable microneedles", it is meant that the microneedles do not dissolve or degrade in vivo, and that they must be removed from the skin.

[0058] Cosmetic treatment process

[0059] The depth of injection of the microneedle into the skin is preferably less than or equal to 250 micrometers, better to 100 micrometers, better still to 50 micrometers.

[0060] This depth range corresponds to the area above the dermo-epidermal junction, and avoids bleeding and pain and thus offers comfortable use of the device.

[0061] Device according to the invention

[0062] The device can cause the micro-needles to pierce the skin at a deep level, and then distribute the composition before removing the device or while removing the device.

[0063] This allows for a good distribution of the composition in the different layers of the skin.

[0064] The device can be connected by wireless communication to an electronic system, in particular a personal computer or a smartphone, for injection control.

[0065] An injection of CO2 gas increases blood flow in the skin, which increases skin oxygenation to reduce the intensity of dark circles.

[0066] Alternatively, the device includes an electronic system.

[0067] Evaluation of skin changes

[0068] Methods for evaluating skin changes can be used, such as optical coherence tomography (OCT), confocal microscopy, electron microscopy, quantitative and qualitative evaluation methods.

[0069] The OCT method can be used to monitor and locate injection sites in the skin.

[0070] The OCT method can be useful for monitoring the volume of gas filled inside the skin, scalp or lips. Preferred modes of implementation

[0071] Preferably, the device according to the invention has one or more of the following characteristics, taken alone or in combination:

[0072] The microneedle is configured to deliver the gas at a flow rate of less than 80 cmVmin, in particular at a flow rate between 20 cmVmin and 60 cmVmin.

[0073] The distribution line includes a pressure regulator.

[0074] The distribution line includes a distribution control switch gas towards the microneedle.

[0075] The distribution line includes an upstream connection line from the pressure regulator to the control switch and a downstream connection line from the control switch to the microneedle.

[0076] The distribution line includes a purge system disposed upstream of the microneedle, to evacuate residual gases stagnating in the microneedle before an injection.

[0077] The purge system has a main body including a valve.

[0078] The purging system includes a two-stage switching mechanism. Description of the figures

[0079] Other features and advantages of the invention will become apparent from the following detailed description, from the schematic and partial, non-limiting examples of its implementation, and from an examination of the accompanying drawing, in which:

[0080] [Fig.1]

[0081] Figure 1 represents a first embodiment of a device that can be used to implement the method according to the invention, comprising an ON / OFF button,

[0082] [Fig.2]

[0083] Figure 2 represents a first purging system that can be used in a device according to the invention, in the rest position.

[0084] [Fig.3]

[0085] Figure 3 represents the purge system of Figure 2 in the first clearance position,

[0086] [Fig.4]

[0087] Figure 4 represents the purge system of Figures 2 and 3 in the second clearance position,

[0088] [Fig.5]

[0089] Figure 5 represents a second purging system that can be used in a device according to the invention.

[0090] [Fig.6]

[0091] Figure 6 shows the operation of the second purging system of Figure 5: A in the rest position, B in the first release position, C in the second release position,

[0092] [Fig.7]

[0093] Figure 7 represents the purging system of Figures 5 and 6 integrated into a device according to the invention, in its rest position.

[0094] [Fig. 8]

[0095] Figure 8 represents the purging system of Figures 5 and 6 integrated into a device according to the invention in the first clearance position,

[0096] [Fig.9]

[0097] Figure 9 represents the purging system of Figures 5 and 6 integrated into a device according to the invention in the second clearance position.

[0098] [Fig. 10]

[0099] Figure 10 shows an optical coherence tomography image of CO2 gas injected according to the method of the invention with microneedles of length equal to 70 pm, for ex vivo pig skin. We obtained equivalent images with microneedles of length equal to 150 pm and 250 pm,

[0100] [Figure 11]

[0101] Figure 11 represents an optical coherence tomography visualization of an area to be treated before CO2 injection, in ex vivo pig skin.

[0102] [Fig. 12]

[0103] Figure 12 represents an optical coherence tomography visualization of the area of ​​Figure 11 after injection of CO2 with a needle of total length equal to 70 pm, into ex vivo pig skin,

[0104] [Fig. 13]

[0105] Figure 13 shows a table comparing the ease / difficulty of injection according to needle length (Ln) and the ratio (IDmoy / Ln), for ex vivo pig skin,

[0106] [Fig. 14]

[0107] Figure 14 shows a photograph of ex vivo pig skin that has been injected at a flow rate of 80 cm³ / min,

[0108] [Fig. 15]

[0109] Figure 15 shows a photograph of ex vivo pig skin that has been injected at a flow rate of 30 cm³ / min,

[0110] The method according to the invention comprises the subcutaneous injection of gas, in particular carbon dioxide (CO2).

[0111] Figure 1 [Fig. 1] illustrates a device 100 according to the invention intended to be brought into contact with the skin of a person to perform a gas injection.

[0112] Skin is for example made up of facial skin, in particular the skin of the dark circles under the eyes.

[0113] This involves, for example, treating the dark circle area to rejuvenate the person's appearance.

[0114] 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.

[0115] Under the effect of the injection, gas bubbles are generated under the skin, which prove effective in improving its appearance.

[0116] 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.

[0117] In the distribution line 20, downstream of the reservoir 10, a pressure regulator 21 can be installed, downstream of which a control button 23 can be placed to release the gas by user command. 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 rule, the control button is in the "OFF" position between two injections and in the "ON" position during injection or just before injection.

[0118] The pressure regulator 21 is optional if the pressure of the gas contained in the tank 10 is equal to the gas pressure required for injection. In this case, the pressure regulator 21 can also be configured with a fixed pressure. It can be controlled by a control knob 18.

[0119] If the pressure of the gas contained in the reservoir 10 is greater than the gas pressure required to perform 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.

[0120] The gas pressure is advantageously between 1.5 bar and 3 bar after passing through the pressure regulator 21.

[0121] 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.

[0122] 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. 1].

[0123] The purging system at rest has been illustrated in [Fig.2].

[0124] Before treatment, it is advantageous to purge the channel of the microneedle 4 to maximize performance and also to prevent contamination. This ensures that the desired volume of gas is actually injected for the treatment, since the residual air present in the microneedle 4 before injection is eliminated by purging and replaced by the desired gas from reservoir 4, such as CO2.

[0125] The purge system 22 comprises a main body 50 including an internal gas passage 53 having a gas inlet 51 through which the gas at a first pressure flow value enters the internal passage 53 through the upstream pipe 80 and a gas outlet 52 through which the gas at a second pressure flow value is extracted from the internal passage 53 through the downstream pipe 81.

[0126] The purge system 22 is also equipped with a control push button 31 which moves in translation along the longitudinal axis A by action of a user on this control button.

[0127] In [Fig.2], the purge system is shown in a "rest position", in which the passage of gas from the upstream line 80 is blocked by the main body 50.

[0128] Figure 3 shows the purge system 22 in a first release position, allowing CO2 gas to pass from the upstream line 80 to the downstream line 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 is moved by the user a distance di along axis A, in order to release the low-pressure gas into the downstream connecting line 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, optionally associated with a ring-shaped seal 37.

[0129] Figure 4 shows the purge system 22 in its second release position for injecting gas under the skin. The push button has been moved by the user a distance d2 along axis A, d2 being greater than dl, in order to release the high-pressure gas into the downstream connecting line 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, optionally associated with a ring-shaped seal 38.

[0130] In the example shown in Figures 2 to 4, the purge system 22 includes a two-stage thrust system, including two springs 56, 66 capable of exerting a constraint on the pressure regulating member 31. Each spring 56, 66 has its own spring length and spring constant, the first spring 56 having a stiffness ki lower than the stiffness k2 of the second spring 66.

[0131] 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.

[0132] At the first push stage ([Fig.3]), when the push button 31 was moved By the user of the distance di along axis A, the resistance of the assembly formed by the first and second springs is defined by the resistance of the weaker spring, i.e., by the resistance of the first spring 56, such that a valve (not shown) allows a limited amount of CO2 gas to pass to the microneedle. The first spring 56 is in an intermediate position between its rest position in [Fig. 2] and its second position in [Fig. 4].

[0133] In the second push stage ([Fig. 4]), when the push button 31 has been moved by the user a distance d2 along 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 to the micro-needle 4 to perform the injection. In this second position, the first spring 56 and the second spring 66 are under maximum stress.

[0134] 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.

[0135] The release means include, by way of example, a release valve cooperating with a valve seat, the release valve being able to be pushed away from its seat by an elastic means.

[0136] 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 consists of a base 72 connected to a PCB, with a push button 74 supported above the base to actuate the purge system.

[0137] The push-button structure was designed for two purposes:

[0138] To mitigate the error of touching or pressing the push button 74 incorrectly,

[0139] Also, to provide a clear pressure sensation when the push button 74 is pressed.

[0140] In the structure, the rubber dome 70 acts as the first spring described in connection with Figures 2 to 4 – to absorb shocks and initiate the downward action with low resistance. The internal spring 71, located within the rubber dome 70, provides greater resistance and allows the passage of gas when the force exerted by the user is sufficient and exceeds a predetermined threshold.

[0141] 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 passage when the user pushes down the dome 70. The internal spring 72 acts as the second helical spring described in connection with Figures 2 to 4, and this provides the resistance to perform the purging and allow the gas to pass from the downstream pipe 81 to the upstream pipe 82.

[0142] These double-action mechanisms exist in mechanical keyboards. There are numerous variations of the two-stage switching system that can be used in the purge system according to the invention.

[0143] Figures 7 to 9 illustrate the operation of the purging 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 purging system has been replaced by the one described separately in Figures 5 and 6.

[0144] The purging system shown in [Fig. 7] uses elastic elements, each with its own elasticity. The materials composing these elastic elements are different and are therefore associated with their own specific elasticity. In this embodiment, the elastic material of the outer dome 70 can be silicone, elastomer, rubber, or sponge.

[0145] In [Fig. 8], the dome 70 provides slight resistance to keep the switch in the closed position. It can be actuated by slight pressure from the user to purge and release gas, in particular CO2, into channel 81. The gas mixes with the residual gas 101 initially present in the microneedle and gradually dilutes this residual gas until it completely fills the internal channel of the microneedle 4. The valve will be allowed to open at a certain gas pressure level, and the user will feel slight resistance from the internal spring 71.

[0146] In [Fig.9], the spring 71 absorbs the higher pressure by changing its shape, and the valve will be fully open for maximum gas delivery.

[0147] The invention is not limited to purging systems equipped with the double-action mechanisms described above. On the contrary, the invention relates to all devices for subcutaneous gas injection equipped with a microneedle purging system, regardless of the structure of this system, to eliminate the gas initially present in the microneedle and decontaminate it, without limiting its application by the specific structure of the embodiment.

[0148] Tests to evaluate the device according to the invention were carried out on ex vivo pigskins.

[0149] 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:

[0150] Microneedle length: 70 µm

[0151] CO2 flow rate: 30 cm3 / min

[0152] Injection time: 10 s

[0153] The pigskin was prepared as follows: untreated, kept in a refrigerator at 5C overnight and used the next day as follows: excised with a scalpel at room temperature, the hairs were cut delicately with surgical scissors so as to keep the skin intact.

[0154] It was placed on a cork sample holder and fixed with pins at the ends so as to keep it taut.

[0155] The OCT equipment used is a Thorlabs Ganymede II.

[0156] CO2 bubbles are observed having penetrated under the skin, located between 100 and 300 um depth. More bubbles are observed when the injected volume is greater. These bubbles disappear in about 10 min.

[0157] It is estimated that CO2 gas could be injected under the skin with needles of length 70 µm, 150 µm and 250 µm and with IDavg / L ratios having values ​​of -—. For all these parameters, gas bubbles are observed under the skin distributed as shown in [Fig. 10].

[0158] 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 s. Bubbles are observed in the dermis. CO2 injection does not induce any apparent skin damage.

[0159] From the table shown in [Fig. 13], we can deduce that:

[0160] a) Length of the microneedle L:

[0161] Up to 150 µm in length, the microneedle is easily injected, without resistance, into the stratum corneum or the epidermis (so as not to reach the dermis). This specification is essential to obtain gas distribution at a shallow depth in the skin.

[0162] A length of 70 pm has proven suitable for injecting CO2 into ex vivo pig skin. CO2 gas is successfully injected with microneedles of 70 pm, 150 pm and 250 pm (total length) into ex vivo pig skin.

[0163] b) IDmny / L Report

[0164] This specification defines the success rate / ease of injection.

[0165] The IDmoy / L ratio is crucial for correct injection: an easy injection was obtained with ID / L < 0.2. Whereas ID / L = 0.86 led to a very difficult injection into ex-vivo human skin.

[0166] Figure 14 shows a photograph of a pig skin ex vivo immediately after treatment with the device according to the invention under the following conditions:

[0167] Microneedle length: 70 pm

[0168] CO2 flow rate: 80 cmVmin

[0169] Injection time: 5 seconds

[0170] Significant swelling is observed around the injection point (shown by an arrow).

[0171] Figure 15 shows a photograph of a pig skin ex vivo immediately after treatment with the device according to the invention under the following conditions:

[0172] Microneedle length: 70 pm

[0173] CO2 flow rate: 30 cmVmin

[0174] Injection time: 5 s

[0175] A very slight swelling is observed in area 36 around the injection point. Comparing the photographs in Figures 14 and 15, it can be concluded that a flow rate of 30 cm³ / min allows for satisfactory control of the injected CO₂ dose, with slight, reversible swelling. A flow rate of 80 cm³ / min is too aggressive and leads to very significant swelling.

Claims

Demands

1. Device (100), in particular cosmetic, 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), the hollow microneedle (4) having an internal channel of mean 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, characterized in that the injection microneedle (4) has a ratio (IDmoy / L) between the mean internal transverse dimension (IDmoy) of the channel and its length (L) of between 0.15 and 0.

86.

2. Device (100), in particular cosmetic, according to claim 1, characterized in that the microneedle (4) is configured to deliver the gas at a flow rate of less than 80 cmVmin, in particular at a flow rate between 20 cmVmin and 60 cmVmin.

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

4. Device (100), in particular cosmetic, according to any one of the preceding claims, characterized in that the distribution line (20) includes a control switch (23) for the distribution of gas to the microneedle (4).

5. Device (100), in particular cosmetic, 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 the control switch (23) and a downstream conduit (81) for connecting the control switch (23) to the microneedle (4).

6. Device (100), in particular cosmetic, according to any one of the preceding claims, characterized in that the distribution line (20) includes a purge system (22) disposed upstream of the microneedle (4), to evacuate, before an injection, residual gases stagnating in the microneedle.

7. Device (100), in particular cosmetic, according to any one of the preceding claims, characterized in that the purging system

8. (22) is provided with a main body (50) including a valve. Device (100), in particular cosmetic, according to any one of claims 6 or 7, characterized in that the purging system (22)

9. includes a two-stage switching mechanism. Kit comprising a device, in particular cosmetic, (100) for the subcutaneous injection of gas as defined according to any one of claims 1 to 8 and a set of spare microneedles (4).

Images