Needle insertion device for electroporation of product into eye

Abstract

The invention relates to a device comprising: a support (4) comprising a support base (10) defining a spherical base contact surface (18) extending along a virtual spherical surface (S) and a circular edge (20) extending in an edge plane (P20); the first and second needles (8a; 8b) that can be moved on the support via a first and a second intermediate piercing position between an extraction and insertion position in which the first and second needles are respectively outside and maximally inserted into the virtual spherical surface, the first and second intermediate piercing positions in which the first and second needles are respectively outside and maximally inserted into the virtual spherical surface. The first and second needles extend along first and second insertion axes ([Delta] 8a, [Delta] 8b), respectively, and the tips thereof lie on first and second insertion points (M8a, M8b) belonging to first and second hemispherical surfaces, respectively, separated by "a median radial plane of edges" of the virtual sphere, the angle ([theta]) between the median radial plane and any insertion axis being between 70 DEG and 110 DEG.

Description

[0001] This application is a divisional application of an invention patent application with an application date of April 24, 2020, an application date number of 202080031406.X (PCT international application number PCT / EP2020 / 061481), and an invention name of “Needle insertion device for electroporating a product into the eye”. Technical Field

[0002] The present invention relates to an insertion device for inserting a needle into an eye, and more particularly to an insertion electrode needle of an electroporation device for injecting a product into the ciliary muscle of an eye. Background Art

[0003] WO 2016 / 166172 discloses an electroporation device for injecting a product into the ciliary muscle of the eye. The device is capable of accurately and stably positioning an electrode needle into the eye.

[0004] However, each needle is inserted approximately tangentially to the surface of the eye. Therefore, when the needle strikes this surface, the impact of the needle may cause the eye to rotate, thereby hindering the insertion of the needle.

[0005] Clamps are known to hold the eye in place. However, they are bulky and require an additional operator.

[0006] There is a need for a solution that facilitates needle insertion without the above mentioned drawbacks.

[0007] It is an object of the present invention to meet this need. Summary of the invention

[0008] To this end, the present invention provides a device, preferably an electroporation device, comprising:

[0009] - a support, including a support base, defining

[0010] - a spherical base contact surface extending along a virtual sphere with a radius between 10 and 15 mm to match the outer surface of the eye, and

[0011] - a rounded edge extending in an edge plane with an axis X and a radius greater than 5 mm and less than 8 mm to match the limbus of the eye;

[0012] a first needle and a second needle, each having a first pointed end and a second pointed end, and being insertable on the support via a first intermediate puncture location and a second intermediate puncture location

[0013] - a first extraction position and a second extraction position, at which the first needle and the second needle are respectively outside the virtual spherical surface, and

[0014] a first insertion position and a second insertion position, at which the first needle and the second needle are respectively inserted to the maximum extent into the virtual spherical surface,

[0015] Move between the first and second intermediate puncture positions, at which the first needle and the second needle extend along the first insertion axis and the second insertion axis, respectively, and the first tip and the second tip are at the first insertion point and the second insertion point, respectively, and the first insertion point and the second insertion point belong to the first hemisphere and the second hemisphere of the virtual sphere, respectively, and the first hemisphere and the second hemisphere are separated by a plane including the axis X and including a center point in the middle of the edge length or the "middle radial plane of the edge".

[0016] In a first aspect of the invention, the first needle and the second needle are movable on the support so that during an insertion operation starting from the first and second withdrawal positions and ending at the first and second insertion positions, the first and second needles press or "squeeze" the virtual spherical surface toward the middle radial plane of the edge when they reach the first and second intermediate puncture positions.

[0017] Preferably, the angle θ between the mid-radial plane of the edge and any one of the first insertion axis and the second insertion axis is greater than 10°, preferably greater than 20°, preferably greater than 30°, preferably greater than 40°, preferably greater than 50°, and / or less than 170°, preferably less than 160°, preferably less than 150°, preferably less than 140°, preferably less than 130°, preferably less than 120°, preferably less than 110°.

[0018] In a second aspect of the invention, the angle between the median radial plane of the edge and either of the first insertion axis and the second insertion axis is greater than 70° and less than 110°. Figures 1 to 6 This embodiment is particularly advantageous when the axial direction is straight as shown.

[0019] Regardless of which aspect of the invention, when the spherical contact surface extends over the outer surface of the eye, the first tip and the second tip compress the eye as they are pushed against the outer surface of the eye.

[0020] As will become clear in the following description, the compression effect advantageously limits the risk of rotation of the eye during insertion of the first and second needles. In addition, compression of the eye can be performed simultaneously with insertion of the tip into the eye so that compression and insertion operations can be achieved by a single operator.

[0021] The device according to the second aspect of the present invention may also have one or more of the following optional and preferred features:

[0022] - the angle between the median radial plane of the edge and the insertion axis of the first needle, preferably the insertion axis of any first needle and / or second needle, preferably the insertion axis of any second needle is greater than 70°, 80° or 85° and / or less than 110°, 100° or 95°, preferably about 90°, the first needle and the second needle being preferably aligned;

[0023] - the angle between the edge plane and the first needle, preferably any first needle and / or the second needle, preferably any second needle is less than 20°, preferably less than 10°, preferably less than 5°;

[0024] - the device comprises a first elastic member and / or a second elastic member arranged to act on the first needle and / or the second needle, respectively, to move the first needle and / or the second needle towards the first extracted position and / or the second extracted position, respectively;

[0025] - the device comprises a first elastic member and a second elastic member, the first elastic member and the second elastic member being configured to apply substantially the same force to the first needle and the second needle, respectively, the force being greater than 1 Newton and less than 10 Newtons;

[0026] - when all first and second needles are in the inserted position, the first needles are staggered with the second needles and / or preferably staggered within a virtual sphere, the first needles extending substantially along the substantial length of the second needles, or vice versa, or

[0027] Alternatively, when both the first needle and the second needle are in the inserted position, the distance between the first tip of the first needle and the second tip of the second needle is less than 1 mm, preferably less than 0.5 mm.

[0028] - the device is an electroporation device and comprises a generator, an invasive electrode electrically connected to a first terminal of the generator and comprising said first and second needles, the support also comprising a plate electrode connected to the second terminal of the generator and defining a plate electrode contact surface extending along a virtual spherical surface;

[0029] - the device comprises: a plurality of first needles, preferably extending in a first needle plane, preferably extending parallel to each other; and / or a plurality of second needles, preferably extending in a second needle plane, preferably extending parallel to each other, all first needles and second needles preferably extending in a common needle plane, preferably extending parallel to each other;

[0030] - the first needle plane and / or the second needle plane and / or the common needle plane are defined as

[0031] - an angle with the median radial plane of the edge greater than 70°, 80° or 85° and / or less than 110°, 100° or 95°, preferably about 90°, and / or

[0032] - the angle with the edge plane is greater than 40° and less than 80°;

[0033] - The device includes

[0034] - an electroporation generator comprising a first terminal and a second terminal having different polarities,

[0035] - an intrusive electrode electrically connected to the first terminal and comprising said first and second pins,

[0036] - a plate electrode fixed to the support, connected to the second terminal and defining a plate electrode contact surface extending along an imaginary spherical surface, the plate electrode contact surface preferably being dimensioned such that the plate electrode contact surface extends substantially in a substantial "plate electrode plane".

[0037] - the first needle plane and / or the second needle plane and / or the common needle plane are substantially parallel to the plate electrode plane;

[0038] - the plate electrode extends in one plane and the first needle plane and / or the second needle plane and / or the common needle plane are substantially parallel to the plane of the plate electrode;

[0039] - when all first and second needles are in their inserted position, i.e. in the fully inserted configuration of said needles, the distance between the needles and the plane of the plate electrode is between 2.0 and 1.3 mm, preferably between 1.8 and 1.5 mm, preferably between 1.7 and 1.6 mm, and is preferably substantially constant whatever point of the plate electrode is considered;

[0040] - The distance between the edge and any point of the contact surface of the plate electrode is greater than 2 mm and less than 6 mm;

[0041] The device comprises an injection needle, the support base comprising a guide adapted to guide the sliding movement of the injection needle between a retracted position and an injection position in which the tip of the injection needle is respectively located outside and inside the virtual spherical surface.

[0042] - preferably, in the injection position, the part of the injection needle extending within the virtual sphere extends in a plane between the common needle plane and the plate electrode plane, preferably in a median plane; preferably parallel to the first needle and the second needle;

[0043] - When the plate electrode is extended to contact the outer surface of the eye, the edge extends over the limbus of the cornea, and the injection needle is fully inserted (injection position), the injection hole of the injection needle opens in the ciliary muscle of the eye;

[0044] - the first needle and the second needle are fixed to the first comb base and the second comb base, respectively, which are substantially symmetrical with respect to the median radial plane of the edge in the insertion position of the first needle and the second needle;

[0045] - In the inserted position of the first and second needles (ie the fully inserted configuration or "insertion position"), each needle appears to penetrate the general plate electrode contact surface when the device is viewed along a viewing direction perpendicular to the plate electrode plane.

[0046] Features of different aspects of the invention may be combined. In particular, optional features of the apparatus according to the second aspect of the invention may be applied to the apparatus according to the first aspect of the invention.

[0047] The device according to the first aspect or the second aspect of the present invention may also have one or more of the following optional and preferred features:

[0048] - the device comprises a first comb base and a second comb base, to which the first needle and the second needle are rigidly fixed, respectively;

[0049] - the device comprises a first arm and a second arm supporting respectively a first needle and a second needle (or a first comb base and a second comb base), the second arm being rotatably mounted on the first arm about an axis, or the first arm and the second arm being rotatably mounted on the support base about different respective axes, or the first arm and the second arm being mounted to translate on the support base, preferably in a common direction;

[0050] - the device comprises a spring which elastically thrusts towards the first extraction position and the second extraction position, respectively, the spring acting for example on the first comb base and the second comb base;

[0051] - the device comprises a synchronization mechanism to synchronize the movement of the first needle and the second needle during said insertion operation, in particular to synchronize the movement of the first comb base and the second comb base, respectively, to which the first needle and the second needle are rigidly fixed;

[0052] The synchronization mechanism comprises a connector having a first branch and a second branch, which is mechanically coupled to a first comb base and a second comb base, to which the first needle and the second needle are rigidly fixed, respectively.

[0053] - the first and second branches define first and second pins which are slidingly mounted in first and second guide tracks defined by the first and second comb bases, respectively, or

[0054] - the first comb base and the second comb base are connected by an elastic joint, and the first branch and the second branch are slidably mounted on the first comb base and the second comb base, respectively, so as to push the first comb base and the second comb base against the action of the elastic joint;

[0055] - the first comb element base and the second comb element base together with the elastic joint form a leaf spring;

[0056] the device comprises a deactivatable lock for locking the synchronizing mechanism at least in an extraction configuration in which the first needle and the second needle are in a first extraction position and a second extraction position and / or in an insertion configuration in which the first needle and the second needle are in a first insertion position and a second insertion position;

[0057] - the device comprises an actuator configured for an operator to act on the synchronization mechanism in order to move the first needle and the second needle simultaneously;

[0058] The device comprises a drive mechanism defining a plurality of predetermined positions in which the first needle and the second needle can be fixed during the insertion operation.

[0059] In one embodiment, the first needle and / or the second needle are curved, preferably so as to extend along a common circle, which is particularly advantageous when the first needle and the second needle are arranged to rotate on the support during the insertion operation, preferably around a common rotation axis close to or containing the center of the circle. Preferably, the distance between the common rotation axis and the center of the circle is less than 5 mm, preferably less than 3 mm, preferably less than 2 mm, preferably less than 1 mm.

[0060] Preferably, in the insertion position of the bent first needle, the distance between any point of the first needle facing the plate electrode and the plate electrode is greater than 0.8 mm, preferably greater than 0.9 mm, preferably greater than 1.0 mm, and / or less than 2.0 mm, preferably less than 1.9 mm, preferably less than 1.8 mm, preferably less than 1.7 mm.

[0061] Preferably, at any insertion position of the bent first needle, the distance between any point of the first needle facing the plate electrode and the plate electrode is greater than 0.8 mm, preferably greater than 0.9 mm, preferably greater than 1.0 mm, and / or less than 2.0 mm, preferably less than 1.9 mm, preferably less than 1.8 mm, preferably less than 1.7 mm.

[0062] Preferably, at any insertion position of the bent second needle, the distance between any point of the second needle facing the plate electrode and the plate electrode is greater than 0.8 mm, preferably greater than 0.9 mm, preferably greater than 1.0 mm, and / or less than 2.0 mm, preferably less than 1.9 mm, preferably less than 1.8 mm, preferably less than 1.7 mm.

[0063] Preferably, at the insertion position of the first needle, the distance between any point of the first needle facing the plate electrode and the plate electrode is substantially constant. In particular, in one embodiment, the first needle is curved and the plate electrode is curved, so that the distance between any point of the first needle facing the plate electrode and the plate electrode is substantially constant. In particular, the plate electrode may be convex, i.e. have a center of curvature outside a virtual spherical surface.

[0064] definition

[0065] The "compression force" corresponds to the force exerted by the needle on the surface of the eye when the needle moves from the withdrawal position to the insertion position and pushes against the surface before penetrating the surface.

[0066] The "insertion point" of the needle is the point at the puncture site where the insertion axis along which the needle extends intersects the imaginary spherical surface bearing the contact surface.

[0067] Two needles are "aligned" when they extend on the same axis.

[0068] A "quadrant of a hemispherical surface" refers to a quarter of the surface of the hemispherical surface obtained by cutting it with two perpendicular planes intersecting along the major axis of the hemispherical surface.

[0069] In the first and second insertion positions of the first and second needles, the device is in an "insertion configuration" or a "fully inserted configuration". In the first and second withdrawal positions of the first and second needles, the device is in an "extraction configuration".

[0070] “First” and “second”, or “upper” and “lower”, or “right hand” and “left hand” are used to distinguish corresponding elements but do not constitute a limitation of the present invention.

[0071] In this specification, unless otherwise stated, "including" does not refer to exclusivity. BRIEF DESCRIPTION OF THE DRAWINGS

[0072] Other features and advantages of the present invention will become apparent upon reading the following non-limiting detailed description and examining the non-limiting accompanying drawings, in which:

[0073] Figure 1 Schematically shows a device according to the invention;

[0074] Figure 2 A perspective view showing an example of a device in contact with the eye according to the present invention;

[0075] Figure 3 An example of a device according to the invention is shown in front view;

[0076] Figure 4 The two combs of the device are shown in the extracted position;

[0077] Figure 5a and 5b Two combs are shown in two examples of the device in the inserted position;

[0078] Figure 6 Two electrodes and a generator according to the invention are shown;

[0079] Figure 7 schematically shows an eye in front view with a device according to the invention in a puncturing position;

[0080] Figure 8-11 and 14-17 schematically illustrate exemplary devices having a synchronization mechanism according to the present invention;

[0081] Fig.12 and 13 Schematically illustrates an exemplary device having a drive mechanism according to the present invention;

[0082] Figures 18 to 21 Schematically illustrating an exemplary device with opposing bases according to the present invention;

[0083] Fig. 22 Schematically illustrates an exemplary device having a convex plate electrode according to the present invention;

[0084] Fig.23 Different embodiments (A to D) of the electrode are schematically shown in the operating position (upper figure), in a side view (middle figure) and in a perspective view (lower figure). The injection needle is only shown in the upper figure.

[0085] In the drawings, the same reference numbers are used to refer to the same or similar elements. DETAILED DESCRIPTION

[0086] The device according to the invention is particularly suitable for electroporation. In this application, it preferably comprises a generator 2 configured for electroporation of a pharmaceutical composition, a support 4 and a first comb 6a and a second comb 6b movable along a sliding direction Δ6.

[0087] The first comb 6a and the second comb comprise first electrode needles 8a and second electrode needles 8b respectively. All electrode needles are electrically connected to a first terminal 9a of the generator 2. Together they define an intrusion electrode.

[0088] The support 4 comprises a support base 10 and a plate electrode 12 fixed to the support base and electrically connected to a second terminal 9b of the generator, the polarity of which is opposite to that of the first terminal.

[0089] The generator is therefore adapted to polarize the plate electrode and the invasive electrode differently in order to generate an electric field enabling electroporation.

[0090] Support

[0091] Support base

[0092] The support base 10 is preferably a polymer material. It is preferably a non-conductive material. It is preferably made of a transparent material for better viewing by the user.

[0093] The support base defines a spherical base contact surface 18 extending along a virtual spherical surface S having a radius of curvature R between 10 mm and 15 mm, preferably between 11 mm and 14 mm, preferably between 12 mm and 13 mm, and preferably about 12.5 mm. The virtual spherical surface S corresponds to the outer surface of the eye O, so that in the working configuration the base contact surface can bear on this outer surface.

[0094] The stability of the support on the eye is thus greatly improved.

[0095] In order to further improve the stability of the support on the eye, the spherical base contact surface 18 preferably supports one, preferably several, spikes protruding from said surface and designed to limit the sliding of the support on the eye. The support preferably comprises more than 2, more than 5, more than 10, more than 20 spikes. The height of the spikes is preferably greater than 0.1 mm and / or less than 0.5 mm or less than 0.3 mm.

[0096] Preferably, the base contact surface 18 has a surface area greater than 50 square millimeters, preferably greater than 100 square millimeters, preferably greater than 120 square millimeters, preferably greater than 140 square millimeters, preferably greater than 150 square millimeters, preferably greater than 160 square millimeters and / or less than 200 square millimeters, preferably less than 180 square millimeters. Preferably, the base contact surface 18 does not extend beyond one quadrant of the hemispherical surface.

[0097] Viewed from the front, the contact surface 18 may have a substantially parallelepipedal profile, for example a rectangular profile, or a substantially trapezoidal profile.

[0098] Preferably, the support base 10 defines a circular edge 20 which partially delimits the contact surface 18 and which is located in an edge plane P 20 Middle extension.

[0099] The edge 20 has a circular arc shape C 20 , with axis X and radius R 20Greater than 5 mm, preferably greater than 5.5 mm, preferably greater than 5.8 mm, and less than 8.0 mm, preferably less than 7.0 mm, preferably less than 7.5 mm, preferably less than 6.0 mm. This edge has a shape that roughly corresponds to the limbus of the eye. It can be placed in contact with the limbus so as to partially surround the limbus.

[0100] When the edge 20 is designed to bear on the limbus of the eye, the stability of the support is greatly improved.

[0101] Preferably, the edge extends laterally over a quadrant angle α of greater than 45°, preferably greater than 60°, preferably greater than 80°, preferably greater than 100°, preferably greater than 120°, preferably greater than 130°, preferably greater than 135°, and / or less than 180°, preferably less than 170°, preferably less than 160°, preferably less than 150°, preferably less than 140°. 20 (See Figure 2 ).

[0102] The support base may preferably comprise a support handle to be gripped, for example, between the thumb and index finger of one hand. Preferably, however, the support handle is optionally provided on the comb.

[0103] Plate Electrode

[0104] The plate electrode 12 is fixed to the support base 10. It defines a plate electrode contact surface 24 which is intended to bear on the outer surface of the eye in the working position. It thus preferably extends along a virtual spherical surface S, e.g. Figure 8 shown.

[0105] The surface area of ​​the plate electrode contact surface is preferably greater than 3 square millimeters, greater than 4 square millimeters, greater than 5 square millimeters, greater than 6 square millimeters, greater than 8 square millimeters, greater than 10 square millimeters, greater than 11 square millimeters, greater than 12 square millimeters, greater than 15 square millimeters, greater than 17 square millimeters, and / or less than 90 square millimeters, less than 60 square millimeters, less than 30 square millimeters, less than 20 square millimeters.

[0106] Preferably, the plate electrode contact surface 24 does not extend beyond one quadrant of the hemisphere. Preferably, it extends about the axis X of the edge (see Figure 1 ) in a quadrant angle α 24 Inwardly extending, the angle is less than 90°, preferably less than 60°, preferably less than 50°, preferably less than 45°, preferably less than 35°, preferably less than 30°, and / or preferably greater than 10°, preferably greater than 15°, preferably greater than 20°.

[0107] In front view, the plate electrode contact surface preferably has a generally rectangular shape.

[0108] The radius of curvature R is relatively large relative to the surface area of ​​the plate electrode contact surface, so that the plate electrode contact surface is substantially in the plate electrode plane P 24 Middle extension.

[0109] Preferably, the distance between the edge 20 and any point of the plate electrode contact surface 24 is greater than 2 mm, preferably greater than 2.5 mm, preferably greater than 3 mm, preferably greater than 3.5 mm, preferably greater than 4.0 mm, and / or less than 6 mm, preferably less than 5 mm, preferably less than 4.5 mm.

[0110] The plate electrode 12 may be a conductive layer partially covering the support base. Preferably, it is not integral with the support base, ie a component initially independent of the support base and then mounted on the support base.

[0111] Comb

[0112] The first comb element 6a and the second comb element 6b are very similar or identical and are assembled on the support in the same way or in a very similar way, so that only the first comb element and its arrangement are described in detail below.

[0113] The second comb element has the same reference numerals as the first comb element, but with an index of "b" instead of "a".

[0114] The first comb member 6a comprises

[0115] - a first comb element base 30a,

[0116] - a straight first electrode needle 8a, which is fixed to the first comb base 30a;

[0117] - preferably a first guide rod 32a, which is fixed to the first comb base 30a, and

[0118] - Preferably, the first elastic member, such as a helical spring 34a or a leaf spring, is configured to urge the first electrode needles towards their extracted position.

[0119] Preferably, all the first electrode needles have the same structure.

[0120] Preferably, the diameter of the first electrode needle, preferably any first electrode needle, is less than 0.5 mm, preferably less than 0.4 mm, preferably less than 0.35 mm. This property is particularly advantageous when the electrode needle is inserted into the eye approximately tangentially to the eye surface, as in the preferred embodiment. For the same reason, the first tip 36a of the first electrode needle, preferably any first electrode needle, is preferably beveled.

[0121] The first comb-like element may include one or more, preferably three, four or five, preferably four, preferably parallel, preferably coplanar, and preferably straight first electrode needles 8a. The distance between the axes of two adjacent parallel first electrode needles 8a is preferably greater than 0.5 mm, preferably greater than 0.6 mm, preferably greater than 0.7 mm, preferably greater than 0.8 mm, and / or less than 5 mm, preferably less than 3 mm, preferably less than 1.5 mm, preferably less than 1.2 mm, preferably less than 1.0 mm, preferably less than 0.9 mm.

[0122] Preferably, the first electrode needle 8a extends in a first needle plane P8, which defines an angle with the edge plane P0 of the edge 20 that is greater than 40°, greater than 45°, preferably greater than 50° and / or less than 80°, preferably less than 70°, preferably less than 60°, preferably less than 55°.

[0123] The first needle plane P8 is preferably substantially perpendicular to the median radial plane Pm of the edge. 20 ( Figure 1 In other words, the first electrode needles are coplanar and preferably each is substantially parallel to the plane P of the edge. 20 extend.

[0124] Preferably, each first electrode needle extends substantially parallel to the plate electrode 12. The first needle plane P8 is parallel to the plate electrode plane P 24 The angle between the first needle plane P8 is preferably less than 20°, preferably less than 15°, preferably less than 10° or less than 5°. The first needle plane P8 is preferably substantially parallel to the plate electrode plane P 24 .

[0125] The distance δ between the two planes is preferably between 2.0 and 1.3 mm, preferably between 1.8 and 1.5 mm, preferably between 1.7 and 1.0 mm, preferably approximately 1.65 mm.

[0126] Each first electrode needle 8a is moved and guided between a first extreme (i.e., limited by the base) insertion position and a first withdrawal position by sliding the first guide rod 32a in the guide of the support base 10, wherein the first insertion position and the first withdrawal position protrude and do not protrude in the virtual spherical surface S, respectively.

[0127] Preferably, in the first insertion position, any first electrode needle defines an angle ω with the outer surface of the eye of less than 40°, preferably less than 25°, preferably less than 10°. Thus, the first electrode needle penetrates the eye substantially tangentially.

[0128] Preferably, the length of the first electrode needle is determined so that in the inserted position, in a front view, i.e. when viewed perpendicularly to the first needle plane P8, the first electrode needle 8a appears to pass approximately completely through the plate electrode contact surface (i.e. extend approximately from one side of the plate electrode contact surface to the opposite side).

[0129] Preferably, the length of the first electrode needle is greater than 4 mm, preferably greater than 6 mm, preferably greater than 8 mm, preferably greater than 10 mm, preferably greater than 11 mm, and / or less than 15 mm, preferably less than 14 mm, preferably less than 13 mm.

[0130] Preferably, the first comb 6a comprises a first comb handle 38a extending substantially parallel to the median radial plane of the edge and preferably substantially perpendicular to the first needle plane P8 so that the operator can push the first comb 6a towards the support without interference by the patient's nose.

[0131] Preferably, the force required to move the first comb against the spring 34a is greater than 1 Newton, preferably greater than 4 Newtons, and / or less than 20 Newtons, preferably less than 10 Newtons. Advantageously, the spring 34a limits the risk of injury when an operator manipulates the device.

[0132] The second comb is similar to the first comb and preferably substantially identical.Preferably, the second comb base is configured such that in the inserted position of the first and second needles it is substantially symmetrical to the first comb base relative to a median radial plane of the edge.

[0133] The second electrode needles extend in a second needle plane parallel to the first needle plane, preferably identical to the first needle plane. In order to avoid collisions between the first electrode needles and the second electrode needles, their respective axes must be offset. Preferably, they are staggered with each other, i.e. in the needle plane, the first electrode needles alternate with the second needles, e.g. Figure 5a shown.

[0134] Preferably, if Figure 1 As shown, the second comb 6b comprises a second comb handle 38b, which is preferably parallel to the first comb handle 38a. The convergence of the two combs towards the support, ie the movement of the combs being pushed towards the support, becomes easier and can be achieved with one hand.

[0135] According to the present invention, the two comb-shaped members can slide relative to the support member so that when the plate electrode contact surface 24 is supported on the puncture position on the outer surface of the eye, the edge 20 is supported on the corneal limbus, and the tips of the first electrode needle and the second electrode needle are supported on the outer surface of the eye. When the first comb-shaped member and the second comb-shaped member are pushed toward the support member 4 at the same time, the first tip and the second tip can press the eye.

[0136] At the puncture position, the first electrode needle and the second electrode needle are inserted along the first insertion axis Δ 8a and the second insertion axis Δ 8a Extended and supported on the virtual spherical surface S at the first insertion point M 8a and the second insertion point M 8b superior.

[0137] All the first tips 36a of the first electrode needles are along the first compression axis Δ 36a Apply together to the first pressure point M 36a The first pressure F 36a .

[0138] All the second tips 36b of the second electrode needles are along the second compression axis Δ 36b Apply together to the second pressure point M 36b The second pressure F 36b .

[0139] The first compression axis Δ 36a and the second compression axis Δ 36b Substantially parallel to the first and second axes of insertion.

[0140] The angle between the planes perpendicular to the first compression axis and the second compression axis is preferably less than 40°, preferably less than 20°, preferably less than 10°, preferably less than 5°. The first compression axis and the second compression axis are preferably parallel. Preferably, the distance between the first compression axis and the second compression axis is less than 5 mm, preferably less than 3 mm, preferably less than 1 mm. Preferably, the first compression axis and the second compression axis are aligned.

[0141] As a result, the risk of the eye rotating during insertion of the electrode needle is greatly reduced.

[0142] Injection needle

[0143] Preferably, the device comprises an injection needle 42. The injection needle may particularly have one or several features of the injection needles disclosed in PCT / EP2016 / 058138, WO2009 / 122030 or US12 / 921,979, which are incorporated herein by reference. It preferably generally comprises an injection channel having an injection hole.

[0144] The injection needle is preferably not the first electrode needle or the second electrode needle.

[0145] It is guided by the support base 10 between a retracted position and an injection position. The injection position is preferably a base position defined so that the injection orifice is at the first needle plane P8 and the plate electrode plane P 24In between, preferably at mid-length between these planes, preferably so as to be approximately facing the center of the plate electrode contact surface. In the injection position of the injection needle, the injection needle preferably extends parallel to the electrode needle.

[0146] Preferably, the injection needle is configured so that when the plate electrode is extended into contact with the outer surface of the eye with the edge extending over the limbus of the eye and the injection needle is fully inserted, the injection needle opens in the ciliary muscle of the eye.

[0147] Pharmaceutical composition

[0148] In particular, the injected product may be any pharmaceutical composition described in WO / 2006 / 123248, which is incorporated herein by reference, in particular a nucleic acid of therapeutic interest, preferably a deoxyribonucleic acid (DNA) molecule (cDNA, gDNA, synthetic DNA, artificial DNA, recombinant DNA, etc.) or a ribonucleic acid (RNA) molecule (mRNA, tRNA, RNAi, RNAsi, catalytic RNA, antisense RNA, viral RNA, etc.). In one embodiment, the composition comprises a circular DNA fragment.

[0149] In a particularly preferred embodiment, the polynucleotide is a double-stranded circular DNA, such as a plasmid, encoding a product having biological activity. Preferred biologically active agents include, but are not limited to, the biologically active polypeptides or proteins disclosed in WO / 2006 / 123248.

[0150] In another specific embodiment, the electroporation device of the present invention is particularly suitable for performing gene replacement. Therefore, the nucleic acid can encode for an active protein to replace the defective protein naturally expressed in the target tissue. Generally, the defective gene that can be replaced includes but is not limited to the gene that causes the disease disclosed in WO / 2006 / 123248.

[0151] Reagent test kit

[0152] According to the present invention, a kit is envisaged. Such a kit comprises a device according to the present invention and a pharmaceutical composition, and optionally instructions for use.

[0153] The pharmaceutical composition is preferably selected from the pharmaceutical compositions described above.

[0154] Within a kit, the components may be packaged or contained separately.

[0155] Descriptions can be in written, video, or audio form and can be included on paper, electronic media, or even as references to other sources such as websites or reference manuals.

[0156] Other components may also be provided in the kit, such as excipients, carriers, other drugs or adjuvants, instructions for administration of the active substance or composition, and instructions for administration or injection devices.

[0157] method

[0158] The method of the present invention can be used to treat an eye disease in a subject, and the pharmaceutical composition is preferably selected from the pharmaceutical compositions described above.

[0159] To use the electroporation device according to the present invention, the operator can proceed through the following steps:

[0160] First, the operator connects a reservoir filled with a drug composition to an injection needle, and electrically connects a first electrode (all electrode needles 8 a and 8 b ) and a second electrode (plate electrode 12 ) to first and second terminals of the generator 2 .

[0161] Initially, the first and second electrode needles are in the first and second extracted positions and are preferably partially within the support base 10. The stiffness of the springs 34a and 34b is determined so that both the first and second electrode needles remain in the extracted positions, especially when the operator manipulates the device by means of the handles 38a and 38b.

[0162] To position the device, the operator places the edge 20 on the limbus of the eye O. The placement of the edge 20 on the limbus and the bearing of the spherical plate electrode contact surface 24 on the sclera ensure good stability and very precise positioning of the device. In this particular application, stability is very important because not only the angle between the electrode needles 8a and 8b and / or the injection needle 42, but also the angle with the spherical plate electrode contact surface are very low at the insertion point, i.e. the needle is inserted almost tangentially to this surface, which makes insertion very difficult.

[0163] The operator then pushes the first comb 6a and the second comb 6b toward each other against the action of the first spring 34a and the second spring 34b, respectively, until the puncture configuration, wherein the electrode needles are in their respective puncture positions with their respective tips contacting the outer surface of the eye.

[0164] In the puncture configuration, if the operator continues to push the first comb 6a and the second comb 6b towards each other, he applies pressure to the eye. This pressure is generated by the action of the first electrode needle, which is along the first compression axis Δ 36a Acting on the first pressure point M 36a The first compressive force on the second electrode needle is a first compressive force on the second compressive axis Δ 36b Acting on the second pressure point M 36b superior.

[0165] The spring stiffness is determined so that the tips of the first electrode needle and the second electrode needle come into contact with the outer surface of the eye before any of them pierces the eye. Preferably, the force exerted by the first spring 34a on the first comb-shaped member 6a is the same as the force exerted by the second spring 34b on the second comb-shaped member 6b, so that the tips of the first electrode needle and the second electrode needle come into contact with the outer surface of the eye at approximately the same time. Thus, in the puncture position, they press against said surface, which effectively prevents any rotation of the eye relative to the support base 10.

[0166] Then, the operator continues to push the first comb member 6a and the second comb member 6b toward each other until the electrode needles penetrate the outer surface of the eye.

[0167] The guide rods 32a and 32b are slidably mounted on the support base 10 to guide the movement of the electrode needles until they reach their respective insertion positions.

[0168] The first electrode needles and the second electrode needles then together define a grid extending substantially parallel to the plate electrode contact surface 24 all along the length of the plate electrode contact surface 24 .

[0169] Preferably, the first electrode needles and the second electrode needles are staggered, such as Figure 5a , 23 As shown in B in or D in 23.

[0170] Alternatively, in their respective insertion positions, the first electrode needle and the second electrode needle are not staggered, but are adjacent to each other, such as Figure 5b , 23 As shown in A in 23 or C in 23. The distance between the tip of the first electrode needle (or "first tip") and the tip of the second electrode needle (or "second tip") is preferably less than 2 mm, 1 mm, less than 0.5 mm, preferably less than 0.2 mm. The first tip of the first electrode needle can face the second tip of the second electrode needle (such as Figure 5b and 23 ), or may not face the second tip of the second electrode needle (as shown in C in FIG. Fig.23 as shown in C in the figure).

[0171] Then, the operator inserts the injection needle into the corresponding insertion guide until the corresponding injection position. The previous insertion of the electrode needle makes the position of the support very stable during the insertion of the injection needle.

[0172] In one embodiment, the injection needle comprises a needle stop in front of the grid of electrode needles, preferably in front of the center of the grid, to determine the injection position where the injection hole opens in the ciliary muscle.

[0173] The operator can then inject the composition.

[0174] The device is then placed in the working configuration and the operator sends suitable electrical signals, such as suitable electrical pulses, by means of the generator in such a way as to generate an electric field in the injection zone which promotes electroporation.

[0175] In certain embodiments, an electric field consisting of one or more electric pulses is applied, as described in PCT / EP2016 / 058138.

[0176] When electroporation of the product is complete, the operator disconnects the electrodes from the generator.

[0177] It is now clear that the device according to the invention allows

[0178] - Limit or even inhibit any rotation of the eye while the needle is inserted into the eye;

[0179] - Single operator intervention;

[0180] -Precise and stable positioning of electrodes;

[0181] - Precisely guide the invasive electrode during its insertion into the eye;

[0182] -Precise injection into the eye relative to the limbus;

[0183] - Generates an effective uniform large electric field.

[0184] Of course, the invention is not limited to the embodiments described and shown which are provided by way of illustration.

[0185] In particular, the various embodiments may be combined.

[0186] Furthermore, any features of the device disclosed in PCT / EP2016 / 058138 may be applied to the device according to the present invention unless they are incompatible with the present invention.

[0187] Also, the manipulation member is not limited to the comb handle 38a described above.

[0188] In addition, the device preferably comprises a synchronization mechanism 50 to synchronize the movement of the first comb element base and the second comb element base from the first extraction position and the second extraction position to the first insertion position and the second insertion position, respectively. Preferably, the synchronization mechanism 50 also synchronizes the movement of the first comb element base and the second comb element base from the first insertion position and the second insertion position to the first extraction position and the second extraction position, respectively.

[0189] Preferably, the first and second comb bases are rotatably mounted on the support base about a common axis Y, and the device comprises a synchronizing linkage to mechanically connect the movements of the first and second comb bases.

[0190] The synchronous linkage preferably comprises a connector 54, preferably a rigid connector, which is configured to slide on the first comb base and the second comb base simultaneously, preferably on the first and second guide rails 56 and 56 of the first and second comb bases, respectively ( Figure 8 , 9 ), or slide on the outer sides of the first surface 571 and the second surface 572 of the first comb-like element base and the second comb-like element base ( Fig.10 , 11 ).

[0191] The connector 54 preferably has a "Y" shape. In particular, the first and second branches of the connector 54 may define first and second pins 58 ( 58 ) that slide in the first and second guide rails 56 of the first and second comb members. Figure 8 ).

[0192] In particular, Figure 8 The device includes a support base 10, a button 60 slidably and elastically mounted on the support base 10, a connector 54 having a "Y" shape rigidly fixed to the button 60, and includes a first pin 58 and a second pin 58, which cooperate with the first comb base and the second comb base so that the sliding movement of the button 60 is coupled with the movement of the first comb base and the second comb base between the first insertion position and the second insertion position and the first extraction position and the second extraction position, respectively.

[0193] More precisely, the first and second comb bases are rotatably mounted on the support base about a common axis Y and define first and second guides 56, 56 for first and second pins 58, 58 of the first and second branches (i.e. the branches forming an inverted "V") of the connector 54. Thus, a translation of the rod 54 along its axis Z relative to the support base 10 is converted into a synchronous rotational movement of the first and second comb bases.

[0194] The device may include a first arm 611 and a second arm 612 supporting the first comb base and the second comb base, respectively, guiding the movement of the second arm relative to the first arm. Preferably, the second arm is rotatably mounted on the first arm around an axis W, the two arms being particularly like a pair of scissors, such as Fig.14 shown.

[0195] The movements of the first arm and the second arm may be independent of each other. In particular, the first arm and the second arm may be rotatably mounted on the support base about respective different axes W1 and W2, such as Fig.15 shown.

[0196] Alternatively, the first arm and the second arm may be mounted on the support base to extend in a common direction ( Fig.16 and17 The horizontal direction in the middle) is preferably moved in translation relative to the support base, such as Fig.16 and 17 shown.

[0197] Preferably, the first electrode needle and the second electrode needle are circular, that is, extending along a circle C (see Fig.11 ). The axis Y preferably intersects the center of the circle. The insertion axis of the curved electrode needle is the local direction of the electrode needle at the insertion point. Therefore, when the axis Y intersects the center of the circle, the insertion axis of the first electrode needle and the second electrode needle does not change during the insertion operation, so that the insertion of the first electrode needle and the second electrode needle causes little harm to the patient.

[0198] The operator can Fig. 9 directly on the comb base (see arrow), and / or the device preferably comprises an actuator 60 to control a synchronizing mechanism (e.g. Figure 8 or 9) or directly acting on the first comb element base and the second comb element base ( Figures 14 to 17 ). The actuator 60 may be, for example, a button or a slider.

[0199] Preferably, the device comprises a spring 62 to automatically move the first and second electrode needles towards the first and second extraction positions, respectively. Thus, the action of the spring is opposite to any action of the operator inserting the first and second electrode needles directly or via an actuator on the comb base.

[0200] The spring 62 may be inserted between the synchronization mechanism and the support base, for example between the actuator 60 and the support base 10 ( Figure 8 ), or between the first comb element base and the second comb element base.

[0201] exist Fig.11 In the embodiment of the present invention, the spring 62 is an elastic joint 62' connecting the first comb base and the second comb base. The first comb base and the second comb base and the elastic joint can be leaf springs.

[0202] In a preferred embodiment, the device comprises a deactivatable lock 64 to lock the synchronization mechanism, preferably the actuator 60 or the connector 54, or more generally the first and second electrode needles in one configuration, preferably at least in the unplugged configuration and / or the inserted configuration.

[0203] exist Fig. 9 In the embodiment of FIG. 5 , when the operator pulls the pull tab 65 , the lock 64 is activated, thereby forcing the front sight 67 of the connector 54 through the opening 69 of the base support.

[0204] In a preferred embodiment, the device includes a drive mechanism 66 to control the insertion depth of the electrode needle during insertion of the electrode needle into the eye.

[0205] Fig.12 An example of a drive mechanism 66 is shown that includes a ratchet 68 configured to cooperate with teeth 70 of the connector 54 to lock the connector in a predetermined position. The number of predetermined positions, i.e., the number of ratchet teeth, is preferably greater than 2, 5 or 10 and / or less than 1000, 500, 100 or 50. The connector 58 can be unlocked by pressing a button 60, which is accessible to an operator through an opening 74 of the support base 10 (see Fig.12 The opening 74 allows the connector 58 to translate relative to the support base 10 to change the position of the connector (see Fig.12 ).

[0206] Fig.13 An example of a drive mechanism 66 is shown that includes a rack 76 formed on the connector 54 and driven in translation by the teeth of a first pinion 78. Fig.13 In the embodiment of the present invention, the second pinion 80 is mechanically connected to the first pinion 78 and the actuator 60 (i.e., the thumb wheel), and the operator can access the actuator 60 through the opening 74 of the support base 10. When the operator rotates the actuator 60, the second pinion 80 is rotated (see Fig.13 ), connector 54 translates.

[0207] Further Improvements

[0208] Overview of further improvements

[0209] According to a further improvement, the invention also relates to a device comprising:

[0210] - a support, including a support base, defining

[0211] - a spherical base contact surface extending along a virtual sphere with a radius between 10 and 15 mm to match the outer surface of the eye, and

[0212] - a rounded edge extending in an edge plane with an axis X and a radius greater than 5 mm and less than 8 mm to match the limbus of the eye;

[0213] - a first needle having a first pointed end and being movable on the support via a first intermediate puncture location between

[0214] - a first withdrawal position, in which the first needle is outside the virtual spherical surface, and

[0215] a first insertion position, in which the first needle is inserted maximally into the virtual spherical surface,

[0216] At the first intermediate puncture position, the first tip is located at a first insertion point of a first hemispherical surface belonging to the virtual sphere,

[0217] The device comprises a relative base defining a relative contact surface extending along a second hemispherical surface of the virtual sphere, the first hemispherical surface and the second hemispherical surface being separated by a median radial plane of the edge,

[0218] The first needle is movable on the support so that during an insertion operation starting from a first withdrawal position and ending at a first insertion position, the first needle and the relative contact surface press or "squeeze" the virtual spherical surface toward the middle radial plane of the edge when the first needle reaches the first intermediate puncture position.

[0219] The device according to further development may also have one or more of the following optional and preferred features:

[0220] - the opposing contact surface comprises a point which is symmetrical to the insertion point of the first needle with respect to a median radial plane of the edge;

[0221] - the opposing contact surface comprises a point at an intersection between a virtual spherical surface and a first insertion axis, along which the first needle extends locally at a first intermediate puncture location at the first insertion point;

[0222] - the counter-contact surface bears at least one spike protruding from said counter-contact surface and configured to limit the sliding of the support on the eye, said spike having a height preferably greater than 0.1 mm and less than 0.5 mm;

[0223] the counter base is movable on the support base, preferably rotatably mounted on the support base, or is fixed relative to the support base, the counter base possibly being part of the support base;

[0224] - the device comprises a plurality of first needles, preferably at least three first needles, preferably fixed to a common first comb base, preferably extending parallel to one another in a common first needle plane so as to extend in a first insertion position substantially parallel to a plate electrode contact surface defined by a plate electrode fixed to the support base and extending along a virtual spherical surface;

[0225] - The device comprises a synchronization mechanism to synchronize the movement of the first needle and the relative base during the insertion operation.

[0226] The device may also include one or several features of other embodiments of the present invention.

[0227] Detailed description of further improvements

[0228] The basis of the present invention is to "compress" the eye during the electrode needle insertion operation to fix and stabilize the support on the eye. As described above, according to a preferred embodiment of the present invention, the first comb-shaped member and the second comb-shaped member are used for compression.

[0229] In an alternative embodiment, all the electrode needles of the device are supported by a first comb base and the second comb is replaced by an opposing base to oppose the action of the first electrode needles on the eye, ie to oppose the reaction to this action.

[0230] like Figure 18-20 As in the embodiment of the present invention, the relative base can be fixed relative to the support at least during the insertion operation.

[0231] Fig.18 An example of such an alternative embodiment is described in Figure 8 The embodiment of the present invention is shown in FIG. 1 , but the second comb-shaped member is replaced by the relative base 90. There is no second electrode needle.

[0232] All previously described features not directly or indirectly related to the second needle are applicable to this alternative embodiment.

[0233] The opposing base 90 defines an opposing contact surface 92, which includes a point M 92 , the point M 92 Relative to edge Pm 20 The middle radial plane of the at least one first electrode needle and the insertion point M 8a symmetry.

[0234] Preferably, the device comprises a plurality of parallel first electrode needles fixed to a common first comb base. Preferably, the first electrode needles are arranged to extend in a plane facing the plate electrode 12, preferably substantially parallel to the plate electrode in the first insertion position, e.g. Fig.19 shown.

[0235] The opposing contact surface 92 preferably extends beyond the insertion point M along a direction D perpendicular to a general plane P8 (first needle plane) of the first electrode needle in the first insertion position. 8a , preferably extending beyond any insertion point of the first electrode needle (see Fig.19 ). Preferably, the distance d between the insertion point and the end 93 of the contact surface 92 along the direction D is 93 Greater than 1 mm, preferably greater than 2 mm, preferably greater than 3 mm, and / or less than 10 mm, preferably less than 5 mm.

[0236] The counter contact surface 92 is preferably part of the spherical base contact surface 18 of the support and extends along a virtual sphere S with a radius R between 10 and 15 mm to match the outer surface of the eye.

[0237] The counter contact surface 92 can have a surface from smooth to any roughness, preferably made of a material that is non-aggressive with respect to the surface of the eye, for example made of a polymer made of silicone, sponge, in particular synthetic sponge, polyester, polyorthoester, polymethyl methacrylate or any other flexible medical grade polymer. Preferably, it bears one, preferably several, spikes 94 that protrude from said surface and are designed to limit the sliding of the support on the eye ( Fig.19 ). The opposing contact surface 92 preferably includes more than 2, more than 5, more than 10, more than 20 and / or less than 1000, 500 or 100 spikes 94. The height of the spikes is preferably greater than 0.1 mm and / or less than 0.5 mm or less than 0.3 mm.

[0238] Fig. 20 An example embodiment of a device having opposing contact surfaces 92 in a working position on an eye O is illustrated.

[0239] When the support base 10 is held on the operator's eye and the operator pushes the first comb 6a towards the edge Pm 20 When the middle radial plane of the first comb-shaped element and the support base are pressed towards each other (see FIG. Fig. 20 ), relative contact surface 92 provides at least a partial counteracting force on the eye to react against the force applied by the first needle.

[0240] like Fig.21 As in the embodiment of the present invention, the relative base can be moved relative to the support member base at least during the insertion operation.

[0241] This embodiment also illustrates how the movement of the first electrode needle and the relative base can be synchronized with a synchronization mechanism similar to the mechanisms previously described to synchronize the movement of the first electrode needle and the second electrode needle during the insertion operation.

[0242] In one embodiment, the device comprises said counter-base, but further comprises a second electrode needle, which is in particular movable on the counter-base between a second extraction position and an insertion position.

[0243] All previously described features may also apply to this last embodiment.

[0244] Of course, the invention is not limited to the embodiments described and shown which are provided by way of illustration.

[0245] In particular, the various embodiments may be combined.

[0246] For any embodiment of the present invention,

[0247] - a plane perpendicular to the X-axis,

[0248] - a plane perpendicular to the general direction of the first needle in the first insertion position

[0249] The angle therebetween is preferably greater than 70° and less than 110°, preferably greater than 80° and less than 100°.

[0250] For any embodiment of the present invention,

[0251] - a plane containing the axis X and perpendicular to the median radial plane of the edge,

[0252] - the local direction of the first needle, preferably the local direction of any first needle at the first insertion point of the first needle at the first intermediate puncture position, and / or the general direction of the first needle at the first insertion position

[0253] The angle therebetween is less than 45°, preferably less than 30°, preferably less than 20°, preferably less than 10°, preferably less than 5°, preferably about 0°.

[0254] When the plate electrode 12 extends along the spherical virtual sphere S ( Figure 8 ), it matches the surface of the eye so that contact with the eye is even and comfortable, limiting the risk of injury.

[0255] However, the plate electrode 12 does not necessarily extend along the spherical virtual sphere. In particular, it is advantageous that when the first needle and / or the second needle are in the first insertion position and the second insertion position, they extend parallel to the first needle and / or the second needle, i.e., the distance between the plate electrode and those parts of the first needle and / or the second needle that face the plate electrode when the needle is in the first insertion position and the second insertion position is constant. The area of ​​the first needle and / or the second needle that faces the plate electrode when the needle is in the first insertion position and the second insertion position is defined by Figure 8 and 22 The vertical dotted line L 12 Definition.

[0256] Advantageously, the uniformity of the electric field between the intrusion electrode made of the first needle and / or the second needle and the plate electrode is improved.

[0257] Specifically, in one embodiment, the first needle and / or the second needle extend in a common plane when they are in the first insertion position and the second insertion position, and the plate electrode extends in a plane parallel to the first needle and / or the second needle.

[0258] In one embodiment, when the first needle and / or the second needle are in the first insertion position and the second insertion position (see Fig. 22 or Fig.23 D), the first needle and / or the second needle are along a common spherical surface C 14The plate electrode 12 extends along the spherical surface C 12 Extend, the spherical surface C 12 With the common sphere C 14 The plate electrode 12 is convex in this embodiment. It protrudes within the virtual spherical surface S by a distance greater than, for example, 0.1 mm, 0.2 mm or 0.5 mm. The distance δ between the first needle and / or the second needle and the plate electrode 12 is constant and is a distance of the spherical surface C. 14 and C 12 The difference between the radii.

Claims

1. A needle insertion device, comprising: - a support (4), said support comprising a support base (10) defining a spherical base contact surface (18) extending along a virtual sphere (S) having a radius (R) between 10 and 15 mm to match the outer surface of the eye, and - a circular edge (20) which is located in the edge plane (P 20 ) having an axis X and a radius greater than 5 mm and less than 8 mm to match the corneal limbus; a first needle (8a) and a second needle (8b), each having a first pointed end (36a) and a second pointed end (36b) and being movable on the support between first and second extraction positions and first and second insertion positions via first and second intermediate puncture positions, - at the first extraction position and the second extraction position, the first needle and the second needle are respectively outside the virtual spherical surface, and - at a first insertion position and a second insertion position, the first needle and the second needle are respectively inserted into the virtual spherical surface to the greatest extent, At the first intermediate puncture position and the second intermediate puncture position, the first needle and the second needle are respectively inserted along a first insertion axis (Δ 8a ) and the second insertion axis (Δ 8b ) extends, and the first tip and the second tip are respectively located at a first insertion point (M 8a ) and the second insertion point (M 8b ) on the first insertion point (M 8a ) and the second insertion point (M 8b ) belong to the first hemispherical surface and the second hemispherical surface of the virtual sphere, respectively, the first hemispherical surface and the second hemispherical surface are bounded by a plane including the axis X and including the center point at the middle length of the edge or the "mid-radial plane of the edge" (Pm 20 ), the first needle and the second needle being movable on the support so that during an insertion operation starting from the first withdrawal position and the second withdrawal position and ending at the first insertion position and the second insertion position, the first needle and the second needle press the virtual spherical surface toward the middle radial plane of the edge when reaching the first intermediate puncture position and the second intermediate puncture position, - a synchronization mechanism for synchronizing the movement of the first needle and the second needle during the insertion operation.

2. The needle insertion device of claim 1, wherein the first needle and the second needle are curved.

3. The needle insertion device according to claim 2, wherein the first needle and the second needle extend along a common circle (C) and are arranged to rotate on the support.

4. Needle insertion device according to claim 3, wherein the first needle and the second needle are arranged to rotate on the support around a common rotation axis (Y), the distance between the center of the common circle (C) and the rotation axis being less than 5 mm.

5. The needle insertion device of claim 1, wherein - the first needle is curved, and the plate electrode is curved, so that the distance between any point of the first needle facing the plate electrode and the plate electrode is substantially constant, and / or The second needle is curved, and the plate electrode is curved, so that the distance between any point of the second needle facing the plate electrode and the plate electrode is substantially constant.

6. The needle insertion device according to claim 1, comprising a first arm (611) and a second arm (612), the first arm and the second arm supporting the first needle and the second needle respectively, - the second arm is rotatably mounted on the first arm about an axis (W), or - said first arm and said second arm are rotatably mounted on said support base about different respective axes (W1, W2), or - said first arm and said second arm are mounted to translate on said support base in a common direction.

7. The needle insertion device according to claim 1, comprising a spring (62) which elastically pushes the first needle and the second needle toward the first and second withdrawn positions, respectively.

8. A needle insertion device according to claim 1, wherein the synchronization mechanism includes a connector (54), the connector having a first branch and a second branch, the first branch and the second branch are mechanically connected to the first comb base and the second comb base, and the first needle and the second needle are rigidly fixed to the first comb base and the second comb base, respectively.

9. The needle insertion device of claim 8, wherein - the first branch and the second branch define a first pin and a second pin (58) which slide in a first guide and a second guide (56) respectively, the first guide and the second guide being defined by the first comb base and the second comb base, or The first comb base and the second comb base are connected by an elastic joint (62'), and the first branch and the second branch slide on the first comb base and the second comb base respectively to push the first comb base and the second comb base against the action of the elastic joint.

10. The needle insertion device according to claim 9, wherein the first comb base and the second comb base and the elastic joint together constitute a leaf spring.

11. The needle insertion device according to claim 1 comprises a deactivatable lock (64) to lock the synchronization mechanism at least in a withdrawal configuration and / or an insertion configuration, in which the first needle and the second needle are in the first withdrawal position and the second withdrawal position, and in the insertion configuration, the first needle and the second needle are in the first insertion position and the second insertion position.

12. The needle insertion device of claim 1, comprising an actuator (60) configured for an operator to act on the synchronization mechanism to simultaneously move the first needle and the second needle.

13. The needle insertion device of claim 1, comprising a drive mechanism (66) defining a plurality of predetermined positions for the first needle and the second needle.

14. The needle insertion device of claim 1, comprising - an electroporation generator (2), comprising a first terminal (9a) and a second terminal (9b) having different polarities, - an intrusive electrode electrically connected to the first terminal and comprising the first needle and the second needle, - a plate electrode (12) fixed to the support, connected to the second terminal and defining a plate electrode contact surface (24) extending along the virtual spherical surface.

Images