WO2022193766A1 - Timbre myocardique à micro-aiguille - Google Patents

Timbre myocardique à micro-aiguille Download PDF

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Publication number
WO2022193766A1
WO2022193766A1 PCT/CN2021/140211 CN2021140211W WO2022193766A1 WO 2022193766 A1 WO2022193766 A1 WO 2022193766A1 CN 2021140211 W CN2021140211 W CN 2021140211W WO 2022193766 A1 WO2022193766 A1 WO 2022193766A1
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WIPO (PCT)
Prior art keywords
myocardial patch
needle
myocardial
patch
microneedle
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PCT/CN2021/140211
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English (en)
Chinese (zh)
Inventor
李彪
吕世文
陈超
董娟
胡晓明
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宁波迪创医疗科技有限公司
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Publication of WO2022193766A1 publication Critical patent/WO2022193766A1/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/0063—Implantable repair or support meshes, e.g. hernia meshes

Definitions

  • the present application relates to the field of medical devices, in particular to a myocardial patch with microneedles.
  • Heart failure referred to as heart failure
  • Heart failure is the terminal stage of the development of heart disease, and most heart failures start from left heart failure.
  • cardiac assist device such as the Acorn CorCap
  • drug therapy the method of biventricular cladding is used for mechanical enhancement, but these types of devices are all bulky, too much contact with normal myocardium will cause harmful effects on normal myocardium, and drugs
  • heart transplantation is difficult to popularize on a large scale due to the severe shortage of donors.
  • One of its main functions is to provide good mechanical support for the myocardial infarction area, improve the left ventricular remodeling of the heart, and prevent heart failure.
  • most studies mainly focus on the design and selection of the material and structure of the myocardial patch, but how to ensure that the myocardial patch can be quickly, effectively and micro-invasively fixed to the target tissue has become an urgent problem to be solved.
  • the common parachute ventricular isolation device has an umbrella frame and umbrella legs.
  • the umbrella frame is in the shape of an inverted umbrella.
  • the umbrella legs have a certain height.
  • the umbrella frame and the umbrella legs are fixedly connected.
  • the umbrella frame is surrounded by a rod, and an isolation membrane is arranged on the umbrella stand.
  • the umbrella foot of the device is pressed against the apex of the left ventricle. It is attached to the inner wall of the left ventricle.
  • the edge of the umbrella rod is designed with a pointed tip and is inclined towards the inner wall of the left ventricle to form an anchoring structure for anchoring.
  • the device needs to be ballooned during the placement process, in order to strengthen the anchor.
  • the toroidal anchoring structure formed by the multiple umbrella rods of the device is still prone to device displacement or floating on the left side.
  • this clinical adverse event has been reported; in addition, the degree of volume reduction of the left ventricle by the device is greatly affected by the degree of balloon dilation, so the effect of volume reduction and the improvement of cardiac function vary by patient and cause.
  • the operation techniques of the surgeons vary, so the clinical effect cannot be fully guaranteed; finally, after the device is placed in the ventricular cavity, the umbrella frame and the left ventricular inner wall will form a large cavity, so that most of the umbrella frame is suspended in the air.
  • Patent CN110859996A provides a cardiac patch, the cardiac patch includes: (A) an elastic membrane including a biodegradable material; (B) a porous structure including a biodegradable material ; The elastic membrane is located on the porous structure, and has good mechanical strength and elasticity, degradability and biocompatibility and multi-purpose (such as drug delivery), but the myocardial patch device is sutured to the myocardial infarction heart. Superficial, time-consuming, and traumatic to the heart.
  • Patent US6726920B1 provides an implantable drug-loaded patch, the structure includes two layers of the patch and connecting elements, the first layer is substantially impermeable to the drug, located on the outer surface of the internal organ, so that the first layer and the outer surface of the organ are easily Forms the reservoir structure; a second layer containing the drug-permeable portion is located between the first layer and the organ surface; the connecting element is used to connect the device, refill the reservoir, which provides an adhesive layer on the surface of the patch facing the heart
  • the myocardial patch is adhered to the heart, but in practice, such patches have limited utility because of the considerable amount of adhesive required to securely fasten the myocardial patch to the heart.
  • the adhesive layer is either very thick, resulting in a very bulky patch that is difficult to deliver to the heart, or there is a risk in drug safety and efficacy (as the patch is not adequately attached to the heart after deployment) A compromise between patch migration risk) and ease of delivery.
  • Patent US8974542B2 provides a sterile, cell-free, biodegradable elastomeric patch (in which no therapeutic agent is delivered to the epicardial surface), which has been shown to provide substantial additional mechanical support to improve A spreading effect that usually occurs after myocardial infarction, but models implanted with epicardial patches rely on the patch being sutured continuously around its edges to the surface of the heart, which makes it unsuitable for minimally invasive procedures and increases trauma due to the need for sutures and significantly increase the risk.
  • Patent CN109718196A provides a foldable myocardial patch for targeted delivery of therapeutic agents to the epicardial surface of the heart.
  • the structure is as follows: the myocardial patch
  • the myocardial patch contains two layers for defining the delivery side and the covering side in the expanded state of the myocardial patch, wherein the first layer and the second layer are configured to be preferential in the expanded state of the myocardial patch Release the therapeutic agent to the delivery side of the myocardial patch; at least one storage cavity (defined by the first and/or second layer and configured to contain the therapeutic agent), at least one rim cavity (defined by the first and/or second layer layer defining and configured to contain and release adhesive material), at least one port (in fluid communication with at least one of the rim cavities and configured to receive the adhesive material), the myocardial patch is generally secured in a manner that is The package presses the patch against the cardiac surface to achieve initial self-adhesion of the patch; then, upon completion of delivery of the patch, the more reactive two-component
  • the adhesive has fluidity, shape and curing time on the surface of the heart It is not easy to control; 2. Mild adhesives have little stimulation to the myocardium, but the bonding firmness is poor; reactive adhesives have strong bonding firmness, but there is a large amount of heat release during the reaction. In addition, the development of a suitable medical adhesive requires a longer validation period and therefore longer time for patients to begin to benefit.
  • the purpose of this application is to overcome the deficiencies of the prior art, and to provide a myocardial patch with microneedles for patients with heart failure and requiring interventional therapy.
  • a myocardial patch with microneedles comprising a myocardial patch and a microneedle, the myocardial patch has a porous structure, the myocardial patch has anatomical morphological adaptability, the microneedles are arranged in sequence from the proximal end to the distal end It comprises a needle root, a needle body and a needle tip, wherein the needle body is located between the needle root and the needle tip.
  • the needle root is provided with a blocking structure
  • the needle body and/or the needle tip is provided with an anchoring structure.
  • the myocardial patch with microneedles is a combined structure
  • the myocardial patch is made of elastic material, and has at least a proximal end surface and a distal end surface
  • the needle tip and the needle body are formed from The proximal end surface of the myocardial patch is pierced, and after piercing the entire patch, it protrudes out of the distal end surface.
  • the myocardial patch with microneedles has a one-piece structure, the needle root of the microneedle is fixedly connected to the myocardial patch, and is located inside the myocardial patch; the needle body and the needle tip is located outside the distal end of the myocardial patch, and the compressive strength of the needle body and the needle tip of the microneedle is higher than the compressive strength of the myocardial patch.
  • the myocardial patch with microneedles is a one-piece structure, and in a natural unconstrained state, most or all of the microneedles are embedded in the myocardial patch; under pressure , the myocardial patch is compressed and deformed, so that at least part of the needle body and the needle tip of the microneedle protrude out of the myocardial patch and penetrate into the target myocardial tissue.
  • the anchoring structure is a saw or barb with a free end edge toward the proximal end.
  • the blocking structure is a saw or barb, the free end edge of the saw or barb facing toward the proximal end.
  • the anchoring structure is an elastic sheet with elasticity and shape memory, wherein the proximal end of the elastic sheet is fixedly connected with the distal end of the needle body, and the distal end is in an unconstrained state.
  • the blocking structure is an elastic sheet with elasticity and shape memory, wherein the proximal end of the elastic sheet is fixedly connected with the distal end of the needle body, and the distal end is in an unconstrained state.
  • the blocking structure is in the shape of a thin plate or sheet, and is perpendicular to the needle body.
  • the blocking structure is in the shape of a thin plate or a sheet, and forms a certain angle with the root of the needle.
  • the needle body is provided with an anchoring structure, and the anchoring structure is a barb, which is used to anchor the target tissue to prevent the microneedle from detaching from the target myocardial tissue with the beating of the heart, Unable to have a fixed effect.
  • the needle tip is provided with an anchoring structure, and the anchoring structure of the needle tip is a micron barb.
  • the anchoring structure of the needle tip is a "J-shaped" barb, so that the needle tip and the needle body cannot move distally or proximally in the axial direction of the microneedle, increasing the restraint, thereby enhancing the firmness of the anchorage to the myocardial tissue.
  • the distal region of the microneedle is provided with a magnetic element.
  • the microneedle and the myocardial patch are in a combined structure in vitro, the microneedle is placed at an appropriate position at the proximal end surface of the myocardial patch, and an external force is applied to make the needle tip and the The needle body is inserted from the proximal surface of the patch, and after piercing the entire myocardial patch, it extends out of the distal surface.
  • the fixed connection between the microneedle and the myocardial patch is realized.
  • the needle body is completely placed inside the myocardial patch, and the needle tip is at least partially placed inside the myocardial patch. Under the action of external force, the myocardial patch is compressed and deformed in the thickness direction, so that the needle body and the needle tip are exposed outside the myocardial patch.
  • the microneedle and the myocardial patch are of an integral structure instead of a combined structure.
  • This design has the following advantages: the process is simple and the use is convenient; the needle body and the needle tip are located at the same The myocardial patch can be accurately positioned; it can be ensured that the needle body and the needle tip are both perpendicular to the myocardial patch or maintain a certain angle; the needle root of the microneedle is partially or completely covered on the myocardial patch. In-chip, effectively reducing the risk of thrombosis.
  • the microneedles and the myocardial patch are integrally formed using biocompatible materials by means of 3D printing technology, and the myocardial patch is formed by stacking regular intersecting filaments and has different microstructures , wherein the cross filament dense area or the small area of the porous structure is provided with the needle root, the needle root is evenly distributed inside the myocardial patch, and the cohesive force of the same material is used to achieve the The fixed connection between the needle root and the myocardial patch.
  • the needle body and the needle tip are located at the outer side of the distal surface of the myocardial patch, that is, the side attached to the surface of the heart; wherein the needle body and the needle tip should have higher compressive strength than the myocardial patch. compressive strength of the sheet.
  • the wire diameter of the crossed filaments is 0.1-0.4 mm
  • the center distance between the wire diameters is 0.5-0.8 mm
  • the average porosity is 50%-76%
  • the tensile modulus is 110-780KPa
  • the tensile strength at break is 50 to 250 kPa, preferably 100 to 200 kPa
  • the tensile elongation at break exceeds 60%, preferably 100 to 300%.
  • the myocardial patch is a porous, adaptive elastic structure with good elasticity and stretchability.
  • the myocardial patch is made of non-degradable materials and degradable materials, wherein the non-degradable materials include polyurethane (PU), polytetrafluoroethylene (PTFE), silica gel, polyethylene (PE) , polyester, polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), polyetherketone (PEK), polymethylmethacrylate (PMMA), and degradable materials include poly(1,3-propylene glycol-citric acid) ester), poly(1,4-butanediol-citrate), poly(1,8-octanediol-citrate), poly(1,12-dodecanediol-citrate), Polylactic acid (PLA), polyglyceryl sebacate (PGS), polycaprolactone (PCL), etc., the pore size of the porous structure is micron, and the longitudinal thickness of the myocardial patch is 0.5mm-20mm; A functional coating or
  • the myocardial patch is composed of at least two layers of relatively thin myocardial patches, namely: an upper myocardial patch and a lower myocardial patch.
  • the lower myocardial patch is made of 3D printing, and the needle body and needle tip of the microneedle pass through the porous structure of the lower myocardial patch to realize the connection with the lower myocardial patch.
  • the proximal end of the needle root of the microneedle is located on the proximal end surface of the lower myocardial patch (ie, the surface not in contact with the target tissue), and the needle body and the needle tip are completely located inside the lower myocardial patch.
  • the lower myocardial patch Under the stress state, the lower myocardial patch is compressed and deformed, so that at least part of the needle tip of the microneedle is exposed to the outer side of the distal surface of the lower myocardial patch, that is, the side attached to the surface of the heart; then , using the proximal end surface of the lower myocardial patch as the distal surface of the upper myocardial patch, and using 3D printing technology to print the upper myocardial patch, the advantages of this design are: a) The needle root is located at the The inner parts of the upper myocardial patch and the lower myocardial patch are not exposed, which reduces the risk of thrombosis at the needle root; b) reduces the subsequent positioning and positioning of the microneedles on the myocardial patch.
  • microneedles pass through the porous structure from the central area of the myocardial patch, which helps to shorten the effective length of the needle body, thereby ensuring the uniformity of external force transmission to the microneedles and the effectiveness of fixation to the myocardial surface.
  • the detachable connection structure is a threaded connection, a retractable connection or a wire drawing connection, and through the detachable connection structure, the matching connection between the delivery system and the myocardial patch with microneedles is realized. and disassembly.
  • the distal end of the ejector rod is further provided with an auxiliary structure, and the auxiliary structure is an auxiliary disk with a shape memory function.
  • the curvature of the inner surface of the auxiliary disk is similar or close to the curvature of the surface of the target tissue.
  • the auxiliary structure consists of a plurality of auxiliary rods with shape memory function.
  • the number and positions of the auxiliary rods correspond to the number and positions of the microneedles on the myocardial patch. Since the myocardial patch has good compressibility and is lighter, it is easy to be placed in the outer sheath of the delivery system, saving space.
  • the microneedles consist of two or more identical small microneedles, each of which is connected as a whole by a proximal needle root.
  • the microneedles are laser-cut and shaped from a shape memory material, or integrally formed by 3D printing.
  • the microneedle is composed of at least two identical small microneedles, and each of the small microneedles sequentially includes a needle root, a needle body and a needle tip from the proximal end to the distal end, and is connected to each other through the needle root .
  • the needle root is in a "line-shaped” structure or diverges outward from the center and is in a three-dimensional "bowl-shaped” structure.
  • the distal end of the needle root of the small microneedle is provided with a blocking structure, and the blocking structure is a barb and cooperates with the needle root to limit the myocardial patch in the fixed area. function, so as to effectively prevent the myocardial patch from slipping or even slipping out of the needle body through the porous structure;
  • the needle body is located between the needle root and the needle tip, and the needle body is provided with an anchoring structure, and the anchor The fixed structure is barb or saw.
  • the anchoring structure on the needle body further comprises barbs, and the barbs are elastic pieces, wherein the barbs are elastic, and under the action of an external force, the barbs accompany the
  • the needle body and the needle tip penetrate into the target tissue, and at this time, the angle ⁇ formed by the barb and the needle body and/or the needle tip is small, and the ⁇ value is 5° to 45°, so that It is easier to penetrate into the target tissue, so as to strengthen the anchoring force of the micro-needle to the myocardial tissue, so that the anchoring effect is firmer.
  • the barb With the beating of the heart, when the microneedle is about to be detached from the target tissue, the barb undergoes elastic deformation, and the angle ⁇ between the barb and the needle body and/or the needle tip increases, resulting in a relative resistance , preventing the microneedles from detaching from the target tissue.
  • an anchoring structure is provided on the tip of the microneedle, and the anchoring structure is a "J-shaped" micro-thorn.
  • the needle body and the needle tip of the microneedle are integrated, that is, the small microneedle is an elastic sheet with elasticity and shape memory.
  • the proximal end of the elastic piece is fixedly connected with the distal end of the needle root, and the distal end of the elastic piece is in an unconstrained state and is in the shape of an outer "eight".
  • the blocking structure is a circular arc segment of the transition area between the needle root and the needle body, and is in the shape of an outer "eight" symmetrical to the central axis, and the circular arc segment can fix the myocardial patch.
  • the anchoring structure on the needle tip is an outer "eight"-shaped structure at the distal end of the dome.
  • the structure Under the action of an appropriate external force and/or the connected myocardial patch is not fully deployed, the structure is elastically deformed in a restrained state, and can be placed on the surface of the myocardial tissue at an appropriate angle, that is, the needle body and the The needle tip is perpendicular to the surface of the target tissue.
  • the elastic piece After a certain external force is applied to the needle root, the elastic piece can be inserted into the target tissue together with the needle tip.
  • the distal end of the shrapnel automatically returns to the original external "eight" shape, so as to prevent the microneedle from detaching from the target tissue, so as to realize the myocardial patch with microneedle and the target tissue. fixed connection.
  • the distal end of the elastic piece is further provided with at least a pair of magnetic elements capable of interacting with each other, wherein the magnetic elements are permanent magnet materials, and when the applied external force is withdrawn, in the myocardial tissue, The distal end of the shrapnel automatically returns to its original shape. At this time, the magnetic elements located at the distal end of the shrapnel interact to produce a slight attraction or repulsion phenomenon, so that the two distal ends of the shrapnel have a more obvious outer "eight". ” shape or inner “eight” shape, which further enhances the anchoring effect, thereby realizing the relative fixation of the myocardial patch with microneedles and the target tissue.
  • the microneedles are made of degradable materials, such as zinc-based alloys, magnesium-based alloys, iron-based alloys and other metal materials, or polylactic acid, polycaprolactone, polyglycerol sebacate, polypeptide , Polyamino acid and other polymer materials.
  • degradable materials such as zinc-based alloys, magnesium-based alloys, iron-based alloys and other metal materials, or polylactic acid, polycaprolactone, polyglycerol sebacate, polypeptide , Polyamino acid and other polymer materials.
  • the needle root of the microneedle, the needle body and the needle tip are combined rather than integrated, wherein the needle root diverges from the center to form a "fan-blade" structure, and the
  • the needle root is provided with one or more blocking structures, wherein the blocking structures can be holes and grooves, which are used to define the relative positions of the needle body and the needle tip on the needle root.
  • the microneedle comprises the needle root, the needle body and the needle tip, the needle body and the needle tip are integral structures, and the needle root is knitted by a shape memory material and gathered together, with the center facing the
  • the outer diverging shape, the blocking structure on the needle root is a knitting hole, which corresponds to the position and number of the knitting hole, and at least part of the needle body is fitted with the needle root and is U-shaped or loop-shaped
  • the structure runs through at least two adjacent knitting holes, and each of the needle body and the needle tip is formed by a wire with shape memory passing through the corresponding two knitting holes in sequence.
  • each of the needle body and the needle tip is formed by filaments with shape memory passing through the corresponding three knitting holes in sequence.
  • the needle root is laser-cut from a shape memory material, wherein the needle root diverges from the center to form a three-dimensional "fan blade" structure, and the needle root is provided with one or more A blocking structure, wherein the blocking structure is a hole groove, and each of the needle body and the needle tip is formed by a wire with shape memory passing through the corresponding two hole grooves in sequence, wherein the The needle body is in a U-shaped or back-shaped structure and runs through two adjacent said holes and grooves.
  • the needle root of the microneedle further includes a surrounding body, and the proximal end and/or the distal end of the surrounding body and the needle root are effectively connected or limited in position through the fixing structure, and are wound around the the needle surface.
  • the surrounding body is coated with a functional agent
  • the functional agent has a pro-endothelialization effect
  • the functional agent includes but is not limited to growth factors, such as vascular endothelial growth factor (VEGF), stromal cell-derived factor -1 (SDF-1 ⁇ ), platelet growth factor beta chain (PDGF- ⁇ ) and transforming growth factor beta 1 protein (TGF- ⁇ 1), etc.; in addition, the above functional agents can be developing dots, developing filaments and developing rings, etc., in order to enhance the Visualization of surgery.
  • growth factors such as vascular endothelial growth factor (VEGF), stromal cell-derived factor -1 (SDF-1 ⁇ ), platelet growth factor beta chain (PDGF- ⁇ ) and transforming growth factor beta 1 protein (TGF- ⁇ 1), etc.
  • the above functional agents can be developing dots, developing filaments and developing rings, etc., in order to enhance the Visualization of surgery.
  • the myocardial patch may be a plurality of small-sized circular porous structures, and each piece of the myocardial patch needs at least one of the microneedles to be fixed at the target tissue on the outer surface of the heart .
  • the myocardial patch is a plurality of small-sized elongated porous structures. By placing them on the target tissue surface of the epicardium one by one and compactly, at least one of the microneedles needs to be fixed on each piece of the myocardial patch.
  • the myocardial patch and the microneedle have different shapes and placement positions, and both the myocardial patch and the microneedle are placed inside the myocardium of the left ventricular cavity.
  • the myocardial patch is made of biocompatible material by 3D printing or local sewing, the number is 1 piece, and its shape and size are similar to or close to the left ventricular cavity (the part below the tricuspid valve) ) of the ellipsoid-like three-dimensional structure; in addition, the surface of the myocardial patch is coated with a drug coating to avoid thrombosis.
  • the microneedle is laser-cut from a tube with shape memory
  • the needle root diverges outward from the center and surrounds a three-dimensional structure similar to a parachute, and most of the inner surface of the needle root wraps Covered with a biocompatible film, the film has biocompatibility and a smooth surface, which can effectively prevent thrombosis.
  • the material of the film includes polyethylene terephthalate (PET), polytetrafluoroethylene (PTFE), polyurethane (PU), polypropylene (PP), parylene, Mucopolysaccharide sulfate (heparin), the shape enclosed by the film is the same as or similar to the parachute-like three-dimensional structure enclosed by the needle root, and through a specific process, the film is completely attached to all needle roots Under the action of external force, the film and the needle root will not slip and peel off relative to each other, which plays the role of isolating and reducing the volume of the ventricle.
  • the specific area of the proximal end of the needle root is not covered with the membrane, and this partial area passes through the corresponding position of the myocardial patch, and is placed and fixed at the apex of the heart.
  • At least two rows of acupuncture should be set on the needle root, and the acupuncture includes the needle body and the needle tip, and is evenly arranged and distributed on the corresponding needle root in a circumferential outward direction, and is consistent with the corresponding
  • the needle root forms a certain included angle ⁇ , and the included angle is 15° ⁇ 90°.
  • one row of the acupuncture is located at the distal end of the needle root (that is, the peripheral area away from the apex) for fixing the edge area of the myocardial patch, and the other row of the acupuncture is located near the needle root.
  • the end ie, the peripheral region near the apex
  • the proximal end of the needle body is provided with a blocking structure and an anchoring structure
  • the blocking structure is a barb
  • the blocking structure cooperates with the needle root to limit the myocardial patch in the fixed area, thereby The myocardial patch is effectively prevented from slipping or even slipping out of the needle body through the porous structure.
  • the distal end of the needle body and/or the needle tip are provided with anchoring structures.
  • the anchoring structure is a saw thorn or a barb. Under the action of external force, the anchoring structure can penetrate into the target tissue with the needle tip, and enhance the anchoring effect on the target tissue, preventing the Beating, the needle tip, or even the entire microneedle, is detached from the target tissue.
  • the combination of the myocardial patch and the microneedle is an in vitro combination
  • the microneedle is placed inside the myocardial patch, and first, the proximal end of the needle root is passed through the The corresponding position in the porous structure of the myocardial patch, and secondly, the acupuncture at the proximal end of the needle root passes through the proximal area of the myocardial patch in turn to ensure that the proximal area of the microneedle is connected to the myocardial patch.
  • the proximal area is fully fitted and secured with no bulges.
  • acupuncture at the distal end of the needle root passes through the distal region of the myocardial patch in sequence, so as to ensure that the distal region of the microneedle and the distal region of the myocardial patch are completely abutted and have no protrusions.
  • the number of the myocardial patches is at least two, the number and size of the microneedles correspond to the myocardial patches, and each adjacent myocardial patch is compactly placed and fixed on the
  • the surface of the myocardial tissue in the ventricular cavity can effectively reduce the volume of the ventricular cavity and improve the blood pumping capacity, thereby improving heart failure.
  • the proximal surface of the myocardial patch is treated with rounded corners.
  • the fillet R is 2mm.
  • each of the myocardial patches can be placed inside the ventricular cavity in a staggered stacking manner.
  • a The first layer of the myocardial patch, the adjacent patches on this layer are laid neatly and compactly on the endocardial surface of the ventricular cavity, and fixed on the inner surface of the ventricular cavity through the microneedles.
  • the top of the layer of myocardial patches is placed on the second layer of the myocardial patches, and the second layer of the myocardial patches is composed of a plurality of the myocardial patches of small size.
  • Each of the myocardial patches in the second layer is staggered and placed between two adjacent myocardial patches in the first layer, and the adjacent patches on this layer are neatly and compactly laid out on all the myocardial patches in the first layer.
  • the second layer of the myocardial patch is pierced into the myocardial patch of the first layer at the corresponding position through the microneedle through the porous structure, so that the second layer of the myocardial patch can be connected with the myocardial patch.
  • the fixation of the myocardial patch in the first layer can effectively reduce the volume of the ventricular cavity, improve the blood pumping ability, and thus improve the heart failure.
  • three or more layers of the myocardial patch can be placed to reduce the volume of the ventricular cavity to a greater extent, improve the blood pumping ability and heart failure situation.
  • the delivery system at least includes an outer sheath tube and a plunger, the inner lumen of the outer sheath tube can accommodate the myocardial patch and/or the microneedle, and the distal end of the plunger is connected to the needle
  • the root is provided with a detachable connection to realize the detachable connection between the two, and an auxiliary structure is provided on the top rod, and the auxiliary structure is used to assist the deployment of the myocardial patch on the target tissue.
  • the microneedle described in this application sequentially includes a needle root, a needle body and a needle tip from the proximal end to the distal end, and the needle root is provided with a blocking structure, which can prevent the myocardial patch in the fixed area. It can effectively prevent the myocardial patch from slipping or even slipping out of the needle body through the porous structure.
  • An anchoring structure is provided on the needle body and/or the needle tip, which can penetrate into the target tissue.
  • the myocardial patch is made of elastic material, the myocardial patch has good elasticity and certain compressibility, and is foldable, and the myocardial patch has an anatomical shape Adaptability, under the action of external force, it can produce good elastic deformation or certain compressibility, so that: 1) the myocardial patch can be compressed and loaded in the outer sheath, or delivered to the target through the lumen of the outer sheath location area, thereby ensuring that the myocardial patch with microneedles of the present application can be implanted into the inner surface of the heart (such as the left ventricular cavity) by percutaneous puncture and minimally invasive intervention through arteries, or can be implanted through a small thoracic incision, through a laparoscope, etc.
  • the inner surface of the heart such as the left ventricular cavity
  • the myocardial patch can be seamlessly fitted with the target tissue to the greatest extent, and the porous
  • the pore size of the structure is in the order of microns, so that the myocardial tissue can grow into the porous structure, thereby increasing the local wall thickness of the myocardial tissue to a certain extent, enhancing the supporting strength of the myocardium, thereby improving the blood pumping function.
  • the myocardial patch with microneedles in the present application has an integrated structure, and this design has the following advantages: a) the process is simple and easy to use; b) each described acupuncture on the myocardium The patch can be accurately positioned; c) it can be ensured that each of the acupuncture needles is perpendicular to the myocardial patch or maintains a certain angle; d) the needle root of the microneedle is partially or completely covered on the myocardial patch. In-chip, effectively reducing the risk of thrombosis.
  • the anchoring structure or the blocking structure in this application is a saw barb or a barb barb, which is used to anchor the target tissue to prevent the microneedle from penetrating the target myocardial tissue with the beating of the heart.
  • the free end edge of the saw barb or barb barb of the anchoring structure faces the proximal end, so that the needle body and the needle tip cannot move far along the axial direction of the microneedle Moving distally or proximally adds restraint, thereby enhancing the firmness of the anchorage to the myocardial tissue.
  • the anchoring structure or the blocking structure in this application is an elastic sheet with elasticity and shape memory, and the distal end of the elastic sheet is fixedly connected with the distal end of the needle body, and the The proximal end of the shrapnel is in an unconstrained state, the proximal end of the blocking structure is fixedly connected with the proximal end of the needle root, and the distal end of the blocking structure is in an unconstrained state, under the action of a certain external force, the microneedle is about to be removed. state when unplugged.
  • the elastic sheet has elasticity, and the elastic sheet penetrates into the target tissue along with the needle tip.
  • the angle ⁇ formed with the needle body and/or the needle tip is small, and the ⁇ value is 5° to 5°. 45°, so that it is easier to penetrate into the target tissue, so as to strengthen the anchoring force of the microneedle in the myocardial tissue, so that the anchoring effect is firmer.
  • the angle ⁇ between the elastic piece and the needle body and/or the needle tip increases, which generates a relative resistance and prevents the microneedle from being detached from the target tissue.
  • the anchoring structure of the needle tip in the present application is a micron barb, or the distal region of the microneedle is provided with a magnetic element, and the magnetic element is a permanent magnet material.
  • the magnetic elements interact with each other in the myocardial tissue, resulting in a slight attraction or repulsion phenomenon, so that the distal ends of the two anchoring structures have a more obvious outer "eight" shape or inner “eight” shape, The anchoring effect is further enhanced, thereby realizing the relative fixation of the myocardial patch with microneedles and the target tissue.
  • the distal end of the microneedle in the present application has a preset shape when it is naturally unconstrained and penetrated into the target tissue, thereby forming the anchoring structure.
  • the delivery system further comprises a needle tube and a thimble, the needle tube is used to load the needle body and the needle tip, the needle tip is provided with an anchoring structure, the needle tube can be pierced into the target tissue, and then the thimble is used for Because the microneedles compressed into a linear state are pushed out from the needle tube, the microneedles are expanded to form a natural and unconstrained shape, and the anchoring structure can play an anchoring role, which can ensure the anchoring effect.
  • the fixed structure is successfully pushed into the target tissue, making up for the defect of insufficient anchoring or failure to successfully penetrate into the heart tissue.
  • the positioning is accurate, it is not easy to slip off, and precise positioning and firm anchoring are achieved.
  • the myocardial patch described in this application is provided with a functional coating or a thin film layer on the surface area that does not contact the target tissue, and the functional coating has biocompatibility and can prevent Adhesion to the pericardium or lung tissue, avoiding affecting the existing normal function of the heart or lung tissue, and ensuring the safety and effectiveness of the myocardial patch.
  • the delivery system at least includes an outer sheath tube and a mandrel
  • the inner cavity of the outer sheath tube can accommodate the myocardial patch and/or the microneedle
  • the distal end of the ejector rod is connected to the
  • the needle root is provided with a detachable connection structure to realize the detachable connection between the two. Therefore, the myocardial patch can be implanted into the target position through the blood vessel or through the endoscopic method with the help of the delivery system, so as to realize the implantation operation.
  • an auxiliary structure is provided on the ejector rod in this application, and the auxiliary structure is used to assist the deployment of the myocardial patch on the target tissue, so that the entire myocardial patch can fit the target tissue to the greatest extent, and accelerate the myocardial
  • the tissue growth and revascularization of the patch also substantially reduces irritation or damage to adjacent tissues or organs of the heart (eg, pericardium, lung, etc.).
  • FIG. 1 is a schematic diagram of the myocardial patch with microneedles in Example 1 of the present application.
  • FIG. 2 is a schematic diagram of the state in which the myocardial patch with microneedles is loaded in the outer sheath according to the first embodiment of the present application.
  • FIG 3 is a schematic diagram of the state when the myocardial patch with microneedles is pushed out of the outer sheath and placed on the surface of the myocardial target tissue in the first embodiment of the present application.
  • FIG. 4 is a schematic diagram of the screw connection structure of the ejector rod and the needle root in the myocardial patch with microneedles in the first embodiment of the application.
  • FIG. 5 is a schematic diagram of the myocardial patch with microneedles in Example 1 of the present application being unfolded into a rectangle on the surface of the target tissue.
  • Fig. 6 is a schematic diagram of a three-dimensional "bowl-shaped" structure in the myocardial patch with microneedles according to the second embodiment of the present application.
  • FIG. 7a to 7c are schematic diagrams of the anchoring structure on the needle body in the myocardial patch with microneedles in the second embodiment of the present application.
  • FIG. 8 is a schematic diagram of the barb in the myocardial patch with microneedles according to the second embodiment of the present application, along with the needle body and the needle tip, piercing into the interior of the target tissue.
  • 9a-9b are schematic diagrams of working process steps of the myocardial patch with microneedles in the second embodiment of the present application.
  • 10 to 12 are schematic structural diagrams when the blocking structures in the myocardial patch with microneedles in Example 3 of the present application are holes and grooves.
  • FIG. 13 is a schematic diagram of the myocardial patch with microneedles in Example 3 of the present application as a plurality of small-sized circular porous structures.
  • FIG. 14 is a schematic structural diagram of the myocardial patch with microneedles placed on the inner side of the myocardium of the left ventricular cavity according to the fourth embodiment of the present application.
  • FIG. 15 is a schematic structural diagram of the myocardial patch with microneedles in Example 4 of the application, which is 3D printed using biocompatible materials.
  • Example 16 is a schematic diagram of the state of the myocardial patch with microneedles in Example 5 of the present application when it is pushed out of the outer sheath and placed on the surface of the myocardial target tissue.
  • 17a to 17c are schematic diagrams of the structure of myocardial patches with microneedles according to different embodiments of the present application.
  • FIG. 18 is a schematic diagram of the structure of the wire passing through the braided hole in an embodiment of the present application.
  • 19a to 19b are schematic structural diagrams of the elastic sheet with magnetic elements in the application.
  • FIG. 20 is a schematic diagram of the surface of the myocardial tissue where a plurality of the myocardial patches in the present application are placed and fixed in the ventricular cavity.
  • FIG. 21 is a schematic diagram of the surface of the myocardial tissue where a plurality of the myocardial patches described in the application are placed and fixed outside the ventricular cavity.
  • FIG. 22 is a schematic diagram of the myocardial patch described in this application being placed inside the ventricular cavity by dislocation stacking.
  • FIG. 23 is a schematic diagram of a drawing connection structure in an auxiliary structure in an embodiment of the present application.
  • 24a-24b are schematic diagrams of the retractable connection structure in the auxiliary structure in another embodiment of the present application.
  • proximal end refers to the end close to the operator
  • distal end refers to the end away from the operator
  • the distal end of the needle root 11 is provided with a blocking structure 4
  • the needle body 11 and/or the needle tip 13 is provided with an anchoring structure 3 .
  • the myocardial patch 2 When the myocardial patch 2 contacts the target tissue of the heart, part of the needle body 12 and the anchoring structure 3 on the microneedle 1 are inserted into the target tissue together with the needle tip 13 .
  • the myocardial patch 2 cooperates with the blocking structure 4 and the anchoring structure 3 to achieve seamless fit and relative fixation of the myocardial patch 2 and the target tissue.
  • the microneedle 1 includes a needle root 11 , a needle body 12 and a needle tip 13 in sequence from the proximal end to the distal end.
  • the blocking structure 4 and the needle root 11 are at a certain angle, and this structure has the following advantages: the blocking structure 4 and the needle root 11 cooperate with each other, and can supplement the myocardium in the fixed area.
  • the sheet 2 plays a limiting role, thereby effectively preventing the myocardial patch 2 from slipping or even slipping out of the needle body 12 through the porous structure.
  • the needle tip 13 is provided with an anchoring structure 3, and the anchoring structure 3 is a barb.
  • the barb can penetrate into the target tissue and cause surrounding tissue.
  • a certain anchoring force is used to fix the microneedle 1 , which effectively prevents the needle body 12 and the needle tip 13 from falling out of the myocardial tissue along with the beating of the heart.
  • the needle tip 13 is located at the distal end of the microneedle 1 and is elongated.
  • the myocardial patch 2 is a porous, self-adaptive elastic structure made of transparent or translucent material, at least having a proximal surface and a distal surface, the myocardial patch 2 has good elasticity and Certain compressibility and foldability, the myocardial patch 2 has anatomical morphological adaptability, and can produce good elastic deformation or a certain compressibility under the action of external force, so that the myocardial patch 2 can be combined with
  • the target tissue can fit seamlessly to the greatest extent, and the pore size of the porous structure is micron-scale, so that the myocardial tissue can grow into the porous structure. Thereby, the local wall thickness of the myocardial tissue is increased to a certain extent, the supporting strength of the myocardium is enhanced, and the blood pumping function is improved.
  • a functional coating or a thin film layer is provided on the surface area of the myocardial patch 2 that is not in contact with the target tissue.
  • the functional coating has biocompatibility and can prevent contact with the pericardium or lung. It can prevent the adhesion of the external tissue, avoid affecting the existing normal function of the heart or lung tissue, and ensure the safety and effectiveness of the myocardial patch 2.
  • the microneedle 1 and the myocardial patch 2 are in vitro combined structures.
  • the microneedle 1 is placed at an appropriate position on the proximal surface of the myocardial patch 2, An external force is applied, so that the needle tip 13 and the needle body 12 are pierced from the proximal end surface of the myocardial patch 2 , and after piercing the entire myocardial patch 2 , they protrude out of the distal end surface.
  • the fixed connection between the microneedle 4 and the myocardial patch 2 is realized by the blocking structure 4 on the needle root 11 .
  • the needle body 12 In a natural state, the needle body 12 is completely placed inside the myocardial patch 2 , and the needle tip 13 is at least partially placed inside the myocardial patch 2 . Under the action of external force, the myocardial patch 2 is compressed and deformed in the thickness direction, so that the needle body 12 and the needle tip 13 are exposed outside the myocardial patch 2 .
  • the blocking structure 4 is a barb, which is used to anchor the target tissue to prevent the microneedle 1 from detaching from the target myocardial tissue with the beating of the heart, and cannot achieve a fixing effect.
  • the edge of the free end faces the proximal end, so that the needle body 12 and the needle tip 13 cannot move distally or proximally along the axial direction of the microneedle 1, which increases the constraint and strengthens the anchoring to the myocardial tissue. firmness.
  • a functional coating is provided on the surface area of the myocardial patch 2 that is not in contact with the target tissue.
  • the functional coating has biocompatibility, has an anti-inflammatory effect, and helps prevent contact with the target tissue. Adhesion.
  • the myocardial patch 2 is made of elastic material, the myocardial patch 2 has good elasticity and certain compressibility, and can be folded, and the myocardial patch 2 has anatomical morphological adaptability, and can withstand external forces. Under the action, good elastic deformation or certain compressibility can be produced, so that: 1) the myocardial patch 2 can be compressed and loaded in the outer sheath 5, or delivered to the target position through the lumen of the outer sheath 5 This ensures that the myocardial patch with the microneedle 1 of the present application can be implanted into the inner surface of the heart (such as the left ventricular cavity) by percutaneous puncture and minimally invasive intervention through arteries, or can be implanted through a small thoracic incision, through an endoscopic microsurgery.
  • the myocardial patch 2 can be seamlessly fitted with the target tissue to the greatest extent, and the porous
  • the pore size of the structure is in the order of microns, so that the myocardial tissue can grow into the porous structure, thereby increasing the local wall thickness of the myocardial tissue to a certain extent, enhancing the supporting strength of the myocardium, thereby improving the blood pumping function.
  • an auxiliary structure 7 is provided on the ejector rod.
  • the auxiliary structure is an auxiliary disk.
  • the radian of the inner surface of the auxiliary disk is similar to or close to the surface radian of the target tissue.
  • the auxiliary structure is used to assist all
  • the myocardial patch 2 is deployed in the target tissue, as shown in FIG. 2 .
  • the delivery system at least includes an outer sheath tube 5 and an ejector rod 6 , the inner cavity of the outer sheath tube 5 can accommodate the myocardial patch 2 and/or the microneedle 1 , and the ejector rod 6
  • a detachable connection structure is provided in the proximal central area of the 2 to realize the detachable connection between the two.
  • the detachable connection structure is a threaded 71 connection, as shown in FIG. Matching connection and disassembly of the delivery system and the myocardial patch 2 with microneedles 1 .
  • the myocardial patch 2 with the microneedles 1 is pushed out of the outer sheath tube 5 and placed on the surface of the myocardial target tissue, as shown in FIG. 3 .
  • the myocardial patch 2 can be smoothly developed into a rectangle on the surface of the target tissue, as shown in FIG. 5 .
  • the myocardial patch 2 push the myocardial patch 2 with the microneedle 1 out of the outer sheath 5, through the initial self-adhesion of the myocardial patch 2 and/or the assistance of the distal auxiliary structure 7 of the delivery system, Therefore, the myocardial patch 2 can be smoothly unfolded into a rectangle on the surface of the target tissue, and through its good elastic deformation or certain compressibility, it can achieve seamless fit with the target tissue.
  • Embodiment 1 The difference from Embodiment 1 is that:
  • the microneedle 1 is composed of two or more identical small microneedles, and each of the small microneedles is connected by the proximal needle root 11 to form a whole.
  • This embodiment has the following advantages: By increasing the number of the microneedles 1, the fixation range of the myocardial patch 2 and the anchoring force to the cardiac tissue are increased.
  • the microneedle 1 is integrally formed by 3D printing from a shape memory material.
  • the needle roots 11 radiate outward from the center and have a three-dimensional “bowl shape” structure.
  • the distances between each of the small microneedles on the needle roots are the same and parallel to each other. Both are at a certain angle with the needle root, and this design has the following advantages: 1) the preparation process is simple; 2) the integrated molding structure is adopted, the overall strength is high, and the force is easier to transmit; 3) it is easy to set on the needle body 12 Anchor structure 3 for enhanced fixation.
  • the anchoring structure 3 on the needle body 11 is a barb 31, as shown in Figures 7a-7c
  • Figure 8 shows the state when the microneedle 1 is about to be pulled out under the action of a certain external force.
  • the barb 31 pierces into the target tissue together with the needle body and the needle tip, so as to penetrate into the target tissue more easily, so as to strengthen the anchoring force of the microneedle 1 to the myocardial tissue , so that the anchoring effect is firmer.
  • the barb 31 With the beating of the heart, when the microneedle 1 is to be detached from the target tissue, the barb 31 produces a relative resistance, preventing the microneedle 1 from detaching from the target tissue. come out.
  • the microneedles 1 are made of degradable materials, such as metal materials such as Zn alloy and Mg alloy, or polymers such as polylactic acid, polycaprolactone, polyglycerol sebacate, polypeptide, and polyamino acid. Material.
  • the microneedle 1 plays a role of fixing, so that the myocardial patch 2 and the target tissue are quickly and effectively fixed. Endothelialization, the myocardial tissue will gradually grow into the porous structure of the myocardial patch, and grow along its corresponding porous structure to realize the effective connection between the myocardial patch 2 and the myocardial tissue.
  • the microneedle 1 also gradually degrades over time.
  • the myocardial patch 2 is pushed out from the outer sheath 5, and with the aid of the auxiliary structure 7 at the distal end of the ejector rod 6,
  • the myocardial patch 2 is exemplarily deployed on the epicardial surface of the heart, and at this stage, one or more of the microneedles 1 are respectively placed at appropriate positions on the myocardial patch, as shown in Figure 9a. Show.
  • Embodiment 1 The difference from Embodiment 1 is that:
  • the needle base 11 of the microneedle 1 is combined with the needle body 12 and the needle tip 13 instead of being an integral type, and the needle body 12 and the needle tip 13 are of an integrated structure.
  • the needle root 11 is provided with one or more blocking structures 4 , wherein the blocking structures 4 may be holes and grooves, which are used to define the needle body 12 and the needle tip 13 on the needle root 11 .
  • the needle root radiates outward from the center to form a "fan-blade" structure, and the needle root 11 is provided with one or more blocking structures 4 .
  • the blocking structure 4 is a hole and groove, which is used to define the relative positions of the needle body 12 and the needle tip 13 on the needle root 11 , as shown in FIG. 10 .
  • This design enables: 1) the lengths of the needle body 12 and the needle tip 13 can be flexibly adjusted; 2) by reasonably setting the thickness of the needle root 11, the spacing of the holes, the length of the holes themselves, the inclination of the needle tip and the number, ensuring Most needle tips can be adaptively anchored to myocardial tissue. 3) described needle tip 13 is micron level, to myocardial tissue micro-damage or no damage, thereby avoiding piercing myocardial tissue, causing risks such as pericardial effusion;
  • the hole groove is a knitting hole 8, and at least a part of the needle body 12 is attached to the needle root, and runs through two adjacent knitting holes 8 in a U-shaped or loop-shaped structure.
  • Each of the needle body 12 and the needle tip 13 is formed by filaments with shape memory passing through the corresponding two knitting holes 8 in sequence, as shown in FIG. 11 .
  • the design has the following advantages: 1) It has good morphological adaptability and can adapt to the shape of the inner and outer surfaces of the heart; b) The metal content of implants is lower; 2) It is easy to achieve minimally invasive; 3) The cost is low; The cross-sectional area of the wire is less than or equal to 0.04 mm 2 , so that the needle body 12 and the needle tip 13 are thin, thereby reducing the trauma to the myocardial tissue.
  • the needle tip 13 is tapered, which is convenient for the microneedle 1 to penetrate into the myocardial target tissue.
  • an anchoring structure 3 is provided on the needle tip at the distal end of the needle root 11 , and the anchoring structure 3 is a "J-shaped" micro-thorn.
  • the "J-shaped" micro-thorn has the following advantages: a) The tiny puncture tip can hang on the internal tissue of the myocardium, avoiding the trauma caused by deep and direct piercing into the myocardial tissue; b) It has an anchoring effect, so that each needle can not be directed distally or proximally along the axis of the microneedle End movement increases restraint and strengthens the firmness of the anchorage to the myocardial tissue.
  • the "J-shaped" micro-thorn Under the action of external force, the "J-shaped" micro-thorn can penetrate into the target tissue with the needle tip 13, and enhance the anchoring effect on the target tissue, preventing the needle tip or even the entire micro-needle from beating with the heart. 1 is detached from the target tissue; the "J-shaped" micro-thorn and the micro-needle 1 are integrally formed by laser cutting, and under the action of external force, the "J-shaped” micro-thorn can penetrate into the target tissue along with the needle tip , produce a certain anchoring force to the surrounding tissue of the needle tip, to a certain extent, enhance the overall anchoring force of the microneedle 1 to the myocardial tissue, preventing the needle tip 13, or even the entire microneedle with the beating of the heart 1 is detached from the myocardial tissue;
  • the needle root 11 of the microneedle 1 further includes a surrounding body 81 , as shown in FIG. 12 , the proximal end and/or the distal end of the surrounding body 81 and the needle root 11 are fixed through the The structure realizes effective connection or position definition, and wraps around the surface of the needle root 11 .
  • This design has the following advantages: it reinforces the needle root 11, thereby enhancing the strength of the needle root 11; 2) the direction of the needle body 12 and the needle tip 13 is limited to a certain extent, which is more beneficial to the needle body 12, The needle tip 13 is perpendicular to the needle root 11 .
  • the surrounding body 81 is wound by a single flexible round or flat wire and wraps most or all of the needle roots 11 .
  • the number of knots of 81 reduces the number of knotted heads, avoids the increase of the retraction and release resistance of the entire microneedle due to too many knotted heads, and also simplifies the production process and improves the production efficiency.
  • the mutual cooperation of the holes and grooves enhances the effectiveness and firmness of the connection, ensures that the surrounding body 81 maintains a predetermined winding shape on the needle root 11, and avoids the surrounding body 81 during the process of entering and exiting the delivery sheath 5. Sliding occurs on the needle root 11 .
  • the surrounding body 81 is wrapped with a functional agent.
  • the myocardial patch 2 may be a plurality of small-sized circular porous structures, as shown in FIG. 13 .
  • the myocardial patch 2 is pushed out from the outer sheath 5, and with the aid of the auxiliary structure 7 at the distal end of the ejector rod 6,
  • the myocardial patch is exemplarily deployed on the epicardial surface of the heart, and at this stage, one or more of the microneedles 1 are placed on the myocardial patch 2 at appropriate positions, respectively.
  • Embodiment 1 The difference from Embodiment 1, Embodiment 4 is:
  • the shape and placement position of the myocardial patch 2 and the microneedle 1 are different.
  • the myocardial patch 2 and the microneedle 1 are both placed inside the myocardium of the left ventricular cavity.
  • It has the following advantages: a) Fixing the myocardial patch 2 with the microneedle 1 on the inside of the myocardial tissue in the left ventricular cavity, to a certain extent, can effectively reduce the volume of the left ventricle and improve the pumping capacity of the heart, thereby Improve heart failure; b)
  • the inner surface of the microneedle base 11 is coated with a smooth biocompatible film 83, which can reduce the risk of thrombosis;
  • the surface of the myocardial patch 2 is rounded and wrapped It is coated with a drug to prevent the formation of blood clots.
  • the myocardial patch 2 is 3D printed using biocompatible materials, and the number is one piece, as shown in FIG. 15 , and its shape and size are similar to or close to the left ventricular cavity (tricuspid valve).
  • the surface of the myocardial patch 2 is coated with a drug coating to avoid thrombosis.
  • the microneedle 1 is laser-cut from a tube with shape memory, and the needle root 11 diverges from the center to form a three-dimensional structure similar to a parachute.
  • Most areas of the inner surface of the root 11 are covered with a layer of biocompatible film 83, the film 83 has biocompatibility and a smooth surface, which can effectively prevent thrombosis.
  • the material of the film 83 is polyethylene terephthalate (PET), polytetrafluoroethylene (PTFE) or polypropylene (PP), and the shape enclosed by the film 83 is the same as the needle root.
  • the enclosed three-dimensional structure similar to a parachute is the same or similar.
  • the film 83 is completely attached to a specific area of the inner surface of all needle roots, as shown in FIG. 19, and under the action of external force, the The thin film 83 and the needle root will not slip and peel off relative to each other, so as to isolate and reduce the volume of the ventricle.
  • the specific area of the proximal end of the needle root 11 is not covered with the membrane 83 , and this part of the area passes through the corresponding position of the myocardial patch 2 and is placed and fixed at the apex of the heart.
  • the acupuncture includes the needle body 12 and the needle tip 13 , and is evenly arranged and distributed in the circumference outward.
  • the corresponding needle root 11 forms a certain included angle ⁇ with the corresponding needle root, and the included angle is 15° ⁇ 90°.
  • one row of the acupuncture is located at the distal end of the needle root 11 (ie: the peripheral area away from the apex), which is used to fix the edge area of the myocardial patch 2, and the other row of the acupuncture is located at the needle root.
  • the proximal end of 11 (ie, the peripheral area near the apex of the heart) is used to fix the proximal area of the myocardial patch 2 .
  • the proximal end of the needle body 12 is provided with a blocking structure 4 and an anchoring structure 3, the blocking structure 4 is a barb, and the blocking structure 4 cooperates with the needle root 11, which can supplement the myocardium in the fixed area.
  • the sheet 2 plays a limiting role, thereby effectively preventing the myocardial patch 2 from slipping or even slipping out of the needle body 12 through the porous structure.
  • the distal end of the needle body 12 and/or the needle tip 13 is provided with an anchoring structure 3 . Wherein, the anchoring structure 3 is a barb. Under the action of external force, the anchoring structure 3 can penetrate into the target tissue with the needle tip 13, and enhance the anchoring effect on the target tissue, preventing the Beating, the needle tip 13, or even the entire microneedle 1, is detached from the target tissue.
  • the combination of the myocardial patch 2 and the microneedle 1 is in vitro, and the microneedle 1 is placed inside the myocardial patch 2 , as shown in FIG. 19 .
  • the acupuncture at the distal end of the needle root 11 is passed through the distal area of the myocardial patch 2 in sequence to ensure that the distal area of the microneedle 1 and the distal area of the myocardial patch 2 are completely fitted and No bulges.
  • the myocardial patch 2 that has been assembled in vitro is crimped and loaded into the outer sheath 5 of the delivery system, and the distal end of the delivery system is placed in the distal end of the delivery system by means of thoracoscope and apical intervention.
  • the apical peripheral area inside the ventricular cavity, and then the myocardial patch 2 with the microneedles 1 is slowly pushed out of the outer sheath 5 in the delivery system.
  • Embodiment 1 The difference from Embodiment 1 is that:
  • the distal end of the microneedle has a preset shape when it is naturally unconstrained and pierced into the target tissue, such as an arc with a reverse bending of 180° as shown in FIG. 16 ,
  • the anchoring structure is further formed.
  • the anchoring structure is formed by heat treatment of materials with shape memory, such as cobalt-chromium alloy and nickel-titanium alloy.
  • the delivery system further includes a needle tube and a thimble, the needle tube is used to load the needle body and the needle tip, the needle tip is provided with an anchoring structure, and the needle tube can penetrate into the target tissue , and then, the ejector needle is used to eject the microneedle compressed into a substantially linear state from the needle tube, so that the microneedle expands to form a natural unconstrained shape, and then the anchoring structure acts as an anchor This can ensure that the anchoring structure is successfully pushed into the target tissue, and make up for the defects of insufficient anchoring or failure to successfully penetrate into the heart tissue.

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Abstract

Timbre myocardique (2) à micro-aiguille (1), comprenant un timbre myocardique (2) et une micro-aiguille (1). Le timbre myocardique (2) a une structure poreuse. Le timbre myocardique (2) présente une adaptation anatomique et morphologique. La micro-aiguille (1) comprend séquentiellement, d'une extrémité proximale à une extrémité distale, une racine d'aiguille (11), un corps d'aiguille (12) et une pointe d'aiguille (13), le corps d'aiguille (12) étant situé entre la racine d'aiguille (11) et la pointe d'aiguille (13). La racine d'aiguille (11) est pourvue d'une structure de blocage (4). Le corps d'aiguille (12) et/ou la pointe d'aiguille (13) est(sont) pourvu(e)(s) d'une structure d'ancrage (3). Lorsque le timbre myocardique (2) entre en contact avec un tissu cible du cœur, une partie du corps d'aiguille ou tout le corps d'aiguille (12) sur la micro-aiguille (1) et la structure d'ancrage (3) pénètrent dans le tissu cible conjointement avec la pointe d'aiguille (13), ce qui permet d'obtenir un ancrage minimalement invasif ou sans lésion. Le timbre myocardique (2), la structure de blocage (4) et la structure d'ancrage (3) coopèrent les uns avec les autres pour réaliser la fixation et la fixation relative du timbre myocardique (2) avec le tissu cible. Le timbre myocardique (2) peut être implanté dans une position cible par l'intermédiaire d'un vaisseau sanguin ou d'un miroir de cavité au moyen d'un système de pose fourni, réalisant ainsi une chirurgie d'implantation minimalement invasive.
PCT/CN2021/140211 2021-03-15 2021-12-21 Timbre myocardique à micro-aiguille WO2022193766A1 (fr)

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CN113069241A (zh) * 2021-03-15 2021-07-06 宁波迪创医疗科技有限公司 一种带微针的心肌补片
CN113907915B (zh) * 2021-09-27 2022-07-29 浙江大学 一种免缝合的凝血辅助固定心脏补片及其制备方法
CN114902973B (zh) * 2022-05-30 2023-11-17 四川御智微科技有限公司 一种新型动物耳标

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