Surface seal for implants

Abstract

The invention relates to an implant for insertion into a body lumen, wherein at least a portion of a surface is arranged to contact a wall of the body lumen and / or a body fluid flowing through the lumen when the implant is inserted into the body lumen. The above-mentioned portion of the surface is covered with a surface seal designed to dissolve within about 30 seconds when the implant is inserted into the body lumen, so that the portion of the surface is exposed to the body lumen. The invention further relates to a method of manufacturing an implant as described above, comprising the steps of obtaining an implant having a surface; providing at least a portion of this surface with a target property; and covering at least a portion of this surface with a surface seal to protect the target property. The invention further relates to an implant kit comprising an implant as defined and use of such an implant for the treatment of an animal or human body, wherein the treatment process comprises dissolving the surface seal covering at least a portion of the surface of the implant by flushing the surface with a dissolving liquid.

Description

[0001] This application is a divisional application of invention patent application No. 201880013727.X, filed on February 23, 2018, entitled "Surface Seal for Implants". Technical Field

[0002] This invention relates to an implant for insertion into a lumen within an organism, as described in the preamble of independent claim 1, and more particularly to an implant in which at least a portion of its surface is arranged to contact a tubular structure corresponding to the lumen and / or to bodily fluids flowing therethrough upon insertion. The invention also relates to the use of such an implant, including rinsing its surface; to a kit of such an implant along with packaging for storage and / or means for inserting the implant; and a method of manufacturing such an implant.

[0003] Such implants for insertion into cavities within the body can be artificial blood vessels, such as stents. The implants according to the invention are not limited to application to vascular tissue, but can take several suitably modified forms to conform to the anatomical structures of cavities and / or cavities within different body organs, whether on the inner or outer walls of such cavities and / or cavities. Therefore, the implants according to the invention can also be intracranial stents or drainage devices; or ocular stents; or coiled or mesh structures of vascular aneurysms; or heart valves; or parts of pacemakers, such as electrodes. Preferably, the implants according to the invention are designed to contact body fluids and be used in anatomical regions, allowing for the dynamic passage of body fluids. Background Technology

[0004] The surface features of implants (e.g., stents) that are designed to be inserted into or onto soft tissue in the body are crucial for the success of treating lumens within the body by applying or inserting the implant. Indeed, such implantation can pose risks to patients, particularly due to inflammatory responses and / or the deposition of unwanted substances from bodily fluids and / or uncontrolled cell proliferation and / or thrombosis on the implant's structure, which in turn can lead to abnormal narrowing or constriction of bodily pathways or openings, commonly referred to as stenosis. Implant surfaces are also susceptible to contamination by deposited organic matter (e.g., naturally occurring hydrocarbon molecules present in the atmosphere of cleanroom manufacturing facilities and on work gloves and / or production equipment in cleanrooms) or non-organic matter (e.g., residues from manufacturing processes such as electropolishing). Implants and corresponding insertion devices, as described above, should be as free from any such contamination as possible. Furthermore, their surfaces should generally be free from dust, fibers, chemical impurities, or particles.

[0005] Therefore, it is common practice to endow implants (such as stents) with targeted surface features, for example, to impart antithrombotic properties to their surface, thereby preventing the accumulation of thrombi. One way to achieve antithrombotic properties is to achieve and maintain a high degree of hydrophilicity on the implant surface, as this reduces platelet adhesion and can also promote frictionless, precise implant insertion (thus limiting potential tissue damage) and promote early tissue healing. Ensuring the biocompatibility of the implant surface and its ability to facilitate rapid and complete healing of body tissues at the application site is highly desirable.

[0006] To provide implant surfaces with these pre-specified target properties, numerous techniques are currently employed, which in particular may include surface coating methods and / or providing implant surfaces with specific macroscopic, microscopic, or nanostructures. One known approach is to modulate the charge state of the implant surface to selectively modulate protein deposits, thereby attempting to allow only those protein deposits to adhere, which can prove advantageous during the post-implantation healing process and exclude unwanted protein deposits. Another known approach to making the implant surface hydrophilic is to remove previously mentioned contaminants from the implant surface, including naturally occurring organic contaminants from the atmosphere (e.g., hydrocarbon deposits). This particular approach does not involve coatings or any other substances adhering to the implant surface. Instead, it is considered a highly purified implant surface that needs to be kept free from recontamination to maintain high hydrophilicity and, therefore, antithrombotic properties. This protective surface layer should not interact with or alter the surface to preserve the originally generated surface properties.

[0007] A conventional method of preservation involves maintaining the implant in an inert storage medium to achieve desired implant surface properties (e.g., hydrophilicity), the inert storage medium being contained in a sealed package to prevent recontamination of the implant. The inert storage medium does not impair the implant surface properties and can be gaseous, liquid, or a combination thereof. In the case of a gaseous storage device, the medium can be, for example, nitrogen or any inert gas. In the case of a liquid storage device, it is typically a sterile solution, such as an isotonic saline solution or another inert solution that does not impair the implant surface properties. Such a system is described, for example, in WO2010 / 000080A1.

[0008] However, the use of inert media reservoirs inevitably complicates the implant manufacturing process, transportation, and handling of the implant before and during implantation. Furthermore, the packaging must meet stringent sealing requirements, and leaks are difficult to detect in the case of gas storage devices.

[0009] Furthermore, airtight and / or liquid-tight packaging limits the possibilities for sterilization; for example, gas sterilization techniques (such as ethylene oxide) are not feasible. Instead, radiation sterilization is suitable. On the other hand, radiation sterilization may damage components of the delivery device made of, for example, certain types of polymers, which would degrade in such cases.

[0010] In particular, liquid preservation solutions or baths present at least part of the weight issue. Especially for large implants, such as long intravascular stents and heart valves, the mass of the liquid significantly increases the final product's weight compared to comparable products in standard packaging. Furthermore, this packaging ultimately becomes bulkier. This leads to increased costs associated with transportation and storage.

[0011] Furthermore, gas reservoirs present at least part of the problem of maintaining the desired chemical and physical properties previously imparted to the implant surface. This is especially true when the implant is removed from its packaging and inserted (or placed) into a lumen within the body. In fact, given that such an implant is exposed to contaminated air upon removal from its packaging, the implant surface may become contaminated during the preparation for implantation.

[0012] Additionally, liquids can act as carriers of impurities to some extent. For example, storing liquids can adversely transfer polymer contaminants from the packaging container itself or from gaskets or other components of the packaging to the surface of the implant.

[0013] Therefore, there is a need for an implant for insertion into a lumen within the body that allows for the stable and reliable retention of surface features acquired through specific processing, and, for example, guarantees a high level of surface purity. It may also be necessary to simultaneously overcome the disadvantages of storing such an implant in an inert medium (gas or liquid and / or a combination thereof):

[0014] - Implant packaging and transportation can be designed with a simplified, less cumbersome approach;

[0015] - Handling implants becomes safer and simpler when packaging them (during the manufacturing process) and when removing them from the packaging (in clinical practice);

[0016] - The scope of disinfection methods is not very limited; and / or

[0017] - Implantation can be performed in situations where there is no excessive emergency associated with the risk of impending loss or damage to the implant's surface features. Summary of the Invention

[0018] According to the invention, this need is addressed by an implant for insertion into a lumen within the body as defined by the features of independent claim 1, the use as defined by the features of independent claim 26, a kit of such implants along with associated packaging as defined by the features of independent claim 29, and a method of manufacturing the implant as defined by the features of independent claim 16. Preferred embodiments are the subject of the dependent claims.

[0019] In particular, the present invention relates to an implant for insertion into a lumen within the body. This implant includes a surface, at least a portion of which is arranged to contact the wall of the lumen and / or bodily fluids flowing therethrough when the implant is in the inserted state. The disadvantages affecting the prior art are overcome by providing a surface sealant to said at least a portion of the implant surface, said surface sealant covering that portion of the implant surface and being soluble when the implant is inserted into the lumen. Advantageously, due to the specific concept of the solution of the present invention, when the surface sealant dissolves, at least a portion of the implant surface covered by the surface sealant is exposed to the lumen within the body. Therefore, it is possible to ensure that the implant is placed in the lumen with a completely pristine implant surface, which is optimally preserved to best cooperate with the tissue wall and / or the bodily fluids of the lumen, particularly in a manner that can prevent thrombosis and / or recurrence of stenosis. In other words, the quality of the implant surface can be maintained while the implant is stored under dry conditions. This preservation is particularly important for hydrophilic scaffolds or similar implants whose surfaces are highly purified and / or highly hydrophilic and are rapidly recontaminated.

[0020] In the context of this invention, the term "when the implant is inserted into a lumen within the body" refers to a time frame / frame in which all necessary steps involved in introducing the implant into the body are performed. This may include at least preparatory steps to prepare the implant for introduction into the body, steps to transfer and deliver the implant within the body, and further preparatory steps prior to final implantation at the target location to achieve implant function. In particular, it may include the steps of: opening the packaging of the implant, preparing the implant for delivery through an opening in the body, delivering the implant through the opening in the body and advancing it forward within the body to the target site until shortly before placing it in the target location. Thus, according to the invention, the surface sealant may dissolve early in the process of opening the packaging and preparing the implant, for example by rinsing it before delivering the implant through the opening in the body. The surface sealant may also dissolve simultaneously with delivering it through the opening in the body and advancing it forward within the body until reaching the target location; or, in the case of a stent, at the latest shortly before inflating it to the target location.

[0021] Surface sealants can be designed to dissolve upon contact with bodily fluids flowing through the body lumen without requiring preventative flushing or partial or complete removal. For example, it can dissolve in blood. Alternatively, it can be designed to be flushed with a solvent (e.g., a saline solution) just before the implant is inserted into the body lumen.

[0022] With this surface sealant, the target properties previously generated or pre-assigned on the implant surface can be optimally preserved, at least until the implant enters the body lumen. In particular, relatively high hydrophilicity can be maintained or preserved, which reduces thrombosis due to lower platelet adhesion on the hydrophilic surface.

[0023] As described above, such pre-assigned target surface properties preferably include antithrombotic properties to prevent thrombus accumulation; adjusted surface charge properties to selectively modulate protein deposits and / or prevent contaminant hydrocarbon deposition; and hydrophilicity to facilitate frictionless, accurate implant insertion, thereby limiting potential tissue damage and early tissue healing. For example, phosphocholine (PC) coated stents have a PC coating on their surface, which allows for reduced thrombotic activity on the stent surface. Such or similar coatings or target surfaces can be protected or preserved by the surface sealant according to the invention. Furthermore, such pre-assigned target surface properties may include pharmaceutical or medical properties. These properties can be imparted to the surface by providing a drug or active pharmaceutical substance, which can also be covered and preserved by the surface sealant. In particular, the surface sealant according to the invention allows for the protection and preservation of the surface of drug-containing implants—such as drug-eluting stents, etc.

[0024] In the context of this invention, an implant for insertion into a lumen or for integral application to a lumen is intended to contact the walls of a typical tubular structure of a lumen and / or contact bodily fluids flowing through the lumen provided by such a tubular structure.

[0025] As used in connection with this invention, the term "in vivo lumen" refers to the internal space of a tubular structure within the human or animal body, or a cavity within the human or animal body. An internal lumen in the sense of this disclosure may take the form of, for example, blood vessels, such as veins or arteries, or coronary or intracranial vessels, or natural heart valves; or tubes of gastrointestinal organs such as the stomach or colon; urinary tract collection tubes or areas of renal ducts, bile ducts, or reproductive organs; tubes of pulmonary bronchial or ocular drainage systems; or cerebrospinal fluid (CSF) drainage.

[0026] On the other hand, the implants described in this disclosure are not suitable for recesses or cavities formed in harder tissues (e.g., bone). The implants according to the invention achieve good biocompatibility with bodily fluids such as blood flowing through and / or around them, as well as with soft tissues growing on the implants, and generally do not absorb or draw blood by clotting, or achieve osseointegration with surrounding bone tissue.

[0027] The implant according to the invention is preferably elastic and flexible, thus capable of being adjusted to fit the shape of a lumen within the body through deformation. For example, such deformation can be induced in the case of stents used in balloon angioplasty; or it can occur by using shape-memory materials and / or braided filaments, for example in the case of self-expanding stents. In the case of stents, the surface sealant may impair mechanical properties, such as its expansion performance. Therefore, according to the invention, the surface sealant preferably dissolves before reaching the target location; or at the latest before the implant expands at the target location. Particularly when implemented as a stent or similar device, the implant can be formed by braiding, knitting, or woven structures or by laser cutting.

[0028] Preferably, but not exclusively, the implant according to the invention comprises a flat, smooth, unroughened surface, unlike the surfaces commonly found in implants, for example, for bone. Such a flat surface may also lack (or may have been intentionally eliminated) any significant roughness, or at least any roughness at the inner surface of the implant, or the waviness of its topology, or any significant texture or coating of any type. This can prove particularly advantageous in supporting thorough cleaning or purification of the implant, and conversely, in preventing contamination from the environment, such as ambient air, storage conditions, or handling. This is the case, for example, with bare metal stents, where no additional coating is contemplated for elution with active substances. In this sense, the preferred, optional absence of specific treatments for integrating complex roughness or peak-valley morphology into the implant according to the invention can prove beneficial in making the implant less susceptible to contamination and thrombosis.

[0029] The term "flat" in connection with possible embodiments of the implant according to the invention can refer to a substantially smooth surface with a roughness ranging from a maximum of 10 micrometers or advantageously a maximum of 5 micrometers. Such a flat surface also places special requirements on the surface sealing material, which must be able to adhere to such a flat surface.

[0030] The surface seal forming a protective layer on the implant according to the invention is preferably designed to dissolve substantially within seconds, i.e., within 30 seconds, or preferably within 20 or 10 seconds, upon contact with blood or a washing buffer or other liquid solution used for device rinsing during preparation. Rapid dissolution of the protective layer is advantageous when inserted into the lumen or during rinsing prior to insertion, allowing a completely pure implant surface to be immediately exposed upon implantation. This is particularly important in the case of expandable or reshapeable implants, such as stents, where flexibility must be maintained during placement. Therefore, a seal that does not dissolve upon first contact with blood or a washing buffer can negatively impact delivery capacity, especially for self-expanding structures where undissolved seals may lock the stent in a certain shape. Rapidly dissolving surface seals also reduce patient exposure to foreign substances.

[0031] Preferably, the surface sealant is configured to dissolve upon insertion into the target location within the intraluminal space. Specifically, the surface sealant is preferably configured to dissolve upon reaching the target location or before implantation at the target location. This allows it to be configured according to a predetermined insertion procedure, ensuring that the surface sealant dissolves upon final implantation. The term "implantation," as used herein, can refer to securing an implant at or within an intraluminal space at the target location. For example, in the case of balloons or self-expanding stents, implantation may be or involves the expansion of the stent at the target location. This surface sealant allows the original mechanical properties of the implant, such as its expansion capabilities, to be preserved, even though its surface is protected by the surface sealant before and ultimately upon insertion. This may be important, for example, when it involves stents or other expandable implants, where proper expansion of the implant may potentially be affected by the surface sealant. In the case of non-expanding stents such as ophthalmic stents, implantation may be or involves placing the stent at the target location.

[0032] Preferably, the surface sealant dissolves before, during, or shortly after insertion into the intravascular lumen, for example, upon contact with bodily fluids passing through the intravascular lumen. Thus, the function of shielding the defined implant surface characteristics remains effective at least from the time the surface sealant is applied throughout production, including packaging, sterilization, storage, transport, and unpacking. Once the implant is fitted and ready for insertion into the intravascular lumen, the function of shielding the implant surface is no longer needed, and the surface sealant can dissolve at this time or at least shortly after insertion into the intravascular lumen. Therefore, the implant received within or on a given intravascular lumen is in an optimal state for ensuring therapeutic success.

[0033] Surface sealants can be composed of or contain a variety of materials that are soluble in a given time and circumstance, and are biocompatible and tight. Therefore, the term "tight" can specifically refer to airtightness, or more specifically, to impermeability to contaminants such as organic deposits (e.g., naturally occurring hydrocarbon molecules present in the atmosphere of a cleanroom production facility and on work gloves and / or production equipment within the cleanroom) or non-organic substances (e.g., residues from manufacturing processes such as electropolishing), dust, fibers, chemical impurities, or particulate matter in general.

[0034] For example, surface sealants can be made from salts such as sodium chloride (NaCl). However, because salts are relatively brittle, they may have the disadvantage of cracking during movement, and therefore may relatively easily detach from the implant surface, especially under exercise or pressure. Surface sealants may also include or contain non-toxic soluble molecules such as carbohydrates and polymers.

[0035] In a preferred embodiment, the surface sealant consists of, or at least contains, a soluble or water-soluble carbohydrate or soluble polymer such as polyethylene glycol, a soluble ionic compound, or a combination thereof that does not directly interact with the implant surface except for sealing it. In experiments implementing the invention, sugar has shown an unexpectedly advantageous ability to stably retain the target properties provided to the implant surface. Therefore, it has been found that a sugar film provided to cover the implant surface according to the invention forms a sealant that shields these surfaces from interaction with contaminants. Sugar is also highly soluble and exhibits an unexpected ability to adhere to and remain attached to the flat surface of the implant according to the invention, even under applied mechanical stress and / or after the sealant has been applied to the surface for a long period (i.e., aging), without detaching from the implant. In fact, sugar has shown remarkable elasticity and conformity to deformation, an advantageous property as it appropriately supports the flexibility and deformability of the implant during vibrations, for example, during storage and / or transport / transportation, which is preferred in this invention. Based on the above, sugar may be a preferred material for the surface sealant according to the invention.

[0036] Soluble carbohydrates used for surface sealants can be monosaccharides or sugar alcohols, such as threitol, erythritol, glucose, fructose, sorbitol, galactose, galactitol, mannose, mannitol, xylitol, inositol or similar substances, organic acids such as citric acid, or other substances such as vitamin C.

[0037] However, soluble disaccharides or trisaccharides, such as trehalose, maltotriose, lactose, lactulose, palaginose, sucrose, or the like, can also be used. In particular, trehalose has proven to be especially suitable for producing the surface seals according to the invention and has also proven to be very stable at high temperatures.

[0038] Surface sealants may also contain compounds made of monosaccharides and / or disaccharides and / or trisaccharides and / or polymeric sugars, optionally in combination with other compounds such as polymers or salts.

[0039] To select the appropriate or optimal material or substance or sealant for a surface sealant, a number of factors should be considered for a given situation or application. Considering the requirements for sealing the surface of vascular implants (e.g., stents) in terms of surface properties, sealant flexibility, clinical operation, quality assurance, manufacturing, sterilization, transportation, and shelf life, a homogeneous, glassy, ​​transparent surface sealant—which is stable yet rapidly dissolves—is generally desirable or beneficial.

[0040] For rapid dissolution and to meet the aforementioned requirements, monosaccharides, disaccharides, and sugar alcohols, as described above, are highly suitable. Furthermore, mixtures of these monosaccharides and disaccharides with salt or sugar alcohols with salt may be beneficial. However, as mentioned above, pure salt sealants may not be suitable; conversely, for example, a combination of trehalose and salt exhibits beneficial sealing properties.

[0041] Larger molecules such as trisaccharides (e.g., glucopyranosyl sucrose) are generally not beneficial because of their low solubility, which may make them difficult to dissolve in the final application. However, in some applications, such slower-dissolving trisaccharide surface sealants may also be advantageous.

[0042] In summary, an ideal surface seal forms a uniform, glassy, ​​transparent, airtight covering that conforms to the implant contour and is flexible for flexible implant structures. It also exhibits good adhesion to the implant surface and / or delivery device (on which the implant is mounted), good solubility (not too fast, not too slow, e.g., within the time ranges mentioned above), good drying properties (not too brittle after drying), stability during sterilization processes such as by radiation or high temperature and / or high humidity ethylene oxide, biocompatibility, and easily adjustable pathways.

[0043] In one example, the suitability of various materials for use as surface sealants has been tested and analyzed. Thus, cobalt-chromium (CoCr) supports have been fitted with different surface sealants, sterilized with ethylene oxide (EtOx) or by radiation (e.g., electron beam) and at 55°C. The sealant was aged at a specific temperature. It was made of carbohydrates, specifically two monosaccharides, two disaccharides, a monosaccharide alcohol, a disaccharide with a salt, polyethylene glycol (PEG) at approximately 6,000 kg / mol, PEG at 10,000 kg / mol, pure salt, ascorbic acid, and citric acid. After aging, the stent and surface sealant were visually inspected. The carbohydrates produced a uniform, transparent layer, while the salt and PEG produced crystalline and exfoliating layers. Except for PEG, all sealant materials retained their hydrophilicity relatively well. In the given test setup, carbohydrates, and combinations of carbohydrates with salts, have been shown to best meet the requirements for vascular implants.

[0044] The thickness of the surface sealant covering the implant surface can range from several hundred micrometers. The sealant can be in the form of a membrane, thin enough to advantageously allow for the movement and flexibility of the implanted component, such as the relative movement of the various parts of the mesh structure of a tubular coronary stent. The thickness can be particularly thinner than the structure it coats.

[0045] In the context of this invention, the implant surface (and therefore at least a portion of the surface arranged to contact the wall of a lumen within the body or the fluid flowing through it) may be made of metal or metal alloy. Polymer materials or ceramic materials, or any combination of these materials, are also possible. In particular, implants according to the invention may be made of cobalt-chromium alloys, platinum-chromium alloys, nitinol, or stainless steel, as well as pyrolytic carbon, silicon carbide, or silicon nitride. Conversely, titanium alloys, which are commonly used in orthopedic surgery, are not particularly preferred except for nitinol, because they are not particularly advantageous for the type of compression and expansion compliance required, for example, in stents, due to their tendency to fracture during such plastic deformation and, moreover, these alloys are generally highly thrombogenic.

[0046] While providing a surface sealant to at least a portion of the implant's surface may be sufficient, it is preferable that substantially all of the implant's surface be covered with a surface sealant. This allows for the complete coverage and protection of the entire surface.

[0047] Implants according to the invention may be, for example, vascular stents or drains for treating bifurcation aneurysms; or ophthalmic stents; or coil-like or mesh structures for treating vascular aneurysms; or artificial or biological heart valves and / or retainers to which these valves are attached; or a portion of a cardiac pacemaker, such as an electrode; or a flow disruptor, such as a coil, mesh structure, or mesh coil; a carotid bridging device; an intra-aneurysmal stent; an occluder; an adjustable remodeling mesh; an aneurysm clip; a vena cava filter; or other filters used during clinical intervention. In the case of cardiac electrodes, the in vivo lumen can be identified as the pericardium. Vascular stents may be intracranial stents, coronary stents, intravascular / peripheral arterial stents, or intravascular / peripheral venous stents; or shunts, such as cerebrospinal fluid (CSF) shunt systems.

[0048] In a preferred embodiment, the surface sealant is homogeneous. Specifically, the surface sealant is homogeneous because it is made from a single composite. Furthermore, the surface sealant can be homogeneous by being more or less uniformly distributed over at least a portion of the surface. Such a homogeneous surface sealant allows for uniform and rapid dissolution and removal before or during insertion.

[0049] Preferably, the surface sealant seamlessly covers at least a portion of the surface. This ensures uniform surface coverage and continuous prevention of contamination.

[0050] Furthermore, the surface sealant is preferably airtight. This type of surface sealant allows for effective prevention of surface contamination through the atmosphere.

[0051] Another aspect of the present invention relates to a method for manufacturing an implant according to the invention for insertion into a lumen within the body, comprising the following steps:

[0052] - To obtain an implant with a surface;

[0053] - To provide targeted properties for at least a portion of such a surface, said surface being configured to contact the wall of a lumen within the body and / or bodily fluid flowing therethrough; and

[0054] - Cover at least a portion of such a surface with a surface sealant to protect the intended target properties.

[0055] The surface sealant can dissolve during the insertion of the implant into the body lumen. In other words, it can dissolve and be metabolized / secreted within the body, or it can be dissolved by flushing before introduction into the body, or a combination thereof. The dissolution process should be completed at the target site no later than the final implementation or implantation of the implant at the target site. As described above, this allows that once the sealant dissolves, a portion of the implant surface previously covered by the surface sealant and preserving the target properties is now exposed to the body lumen, and the implant can perform its medical function without interference from the sealant. The target properties preferably include hydrophilicity. In particular, the implant surface may have relatively high hydrophilicity, which is essentially an antithrombotic property and is protected by the surface sealant.

[0056] The manufacturing method preferably further includes the following steps:

[0057] - A solution that provides a sealant;

[0058] - Immerse the surface of the implant in the solution or spray it with the solution; and

[0059] - Dry the sealant on at least a portion of the surface of the implant to form a surface sealant.

[0060] The surface sealant is physically formed uniformly and consistently on a portion of the desired implant surface, such that the area intended to be sealed is covered or not detached. This can be effectively achieved by applying the sealant in a solution, for example, between 1% and 10%, preferably between 1% and 6%. This method, together with the hydrophilic properties of the stent, allows sealing of narrow cracks, such as at the intersection of two monofilaments in a braid. Due to its hydrophilic properties, applying a soluble surface sealant to a prepared or (highly) hydrophilic surface can achieve uniform and seamless coverage of at least a portion of said surface. This is beneficial for manufacturing reasons and to ensure respective quality / specifications (e.g., ensuring uniform surface coverage), as sealing hydrophobic surfaces may result in uncovered areas because the (aqueous) sealant solution may be repelled in some areas of the surface.

[0061] The term "sealant" can refer to one or more substances that form a seal on the surface of an implant. In particular, it can be a substance that dissolves in a liquid and forms a surface seal when dry.

[0062] Furthermore, the manufacturing method may include the step of placing the implant in or on an insertion device or delivery device. The insertion device may be, for example, a catheter. For instance, a catheter is used to deliver the implant (which may in particular be a stent) to a treatment site within the lumen of a body organ (typically a blood vessel), and to deploy the implant in such a location. Sealing of the implant surface may be performed after or before the implant is placed onto the insertion device, or during the process of placing the implant onto the insertion device.

[0063] When the sealant is dried on at least a portion of the implant's surface, the implant can be disposed in a package, such as an insertion device or a portion thereof. Thus, the sealant binds or integrates the implant into the package, such that the package and the implant form a single unit.

[0064] Preferably, the manufacturing method includes rinsing the delivery device together with the implant to be installed, or rinsing with a sealant solution during implantation. This ensures that the sealant is applied throughout the implant and to other components to be inserted into the body or into a lumen within the body.

[0065] Stents, typically cylindrical in shape, are usually inserted into the body lumen with a reduced diameter and then expanded to the vessel diameter, thereby physically supporting the vessel wall and keeping the vessel unobstructed. In the case of balloon-expandable stents, an angioplasty balloon can be used to activate the stent crimped onto the balloon catheter assembly.

[0066] Additionally, self-expanding stents, similar to drainage devices, flow disruptors, coils, etc., are spring-loaded into the catheter sheath and expand outward into the blood vessel through elasticity. In this case, the stents utilize the shape memory properties of advanced metallic materials such as nitinol (another feature of which is superelasticity), special polymer materials (which may also be biodegradable), or special designs (such as braided structures) and / or combinations thereof.

[0067] In particular, in embodiments where the implant is a stent, the manufacturing method may further include the step of pressing the implant before, during, or after covering at least a portion of the surface with a surface sealant.

[0068] Sealant made from sugars can advantageously be stable and elastic, to the extent that it allows for implant compression without the risk of surface sealant detachment or loosening. Trehalose, for example, has been found to be particularly stable under mechanical and thermal stress and suitable for maintaining previously generated implant surface properties.

[0069] Furthermore, the sterilization step of the implant according to the invention can be performed after the formation of the surface seal by applying radiation or gas. For this purpose, gamma or beta radiation and / or gaseous sterilizing agents, such as ethylene oxide (ETO), can be used.

[0070] Preferably, covering the at least a portion of the surface with a surface sealant includes configuring the surface sealant to dissolve upon reaching the target location within the lumen of the implant. Thus, the surface sealant is preferably configured to dissolve upon implantation at the target location. This configuration of the surface sealant may include obtaining information about the insertion process in which the intended implant is to be delivered and adjusting the surface sealant according to the insertion process such that it dissolves upon reaching the target location. The surface sealant is advantageously configured to dissolve no later than the final deposition of the implant at the target location. This allows the implant to be provided with a surface sealant prepared for the intended insertion process. For example, when the insertion process involves rinsing the implant upon or shortly before entry into the body, the surface sealant may be configured to dissolve in such rinsing. Therefore, it can be ensured that the surface sealant is removed and that the mechanical properties of the implant are available upon reaching the target location.

[0071] Another aspect of the invention relates to an implant kit comprising an implant as defined above and a package configured to protect the surface of the implant. Advantageously, this package further enhances the protection of the surface seal against impact or other mechanical / thermal stresses, scratches, etc., ultimately helping to maintain the target properties imparted to the implant surface. The package may also take the form of an insertion device or part thereof, such as a catheter in which the implant is disposed. For example, such a package may serve as or include a sheath of a catheter or a similar arrangement of catheters and / or its dispenser coil. The package may be made of a polymer or other materials commonly used for packaging, or combinations thereof. It may include a cap for opening and / or closing the package. Furthermore, the cap may be equipped with a puncture-resistant structure, such as a diaphragm or the like. This structure allows, for example, the delivery of a medium such as a solvent, like a saline solution, into the package without opening it, via a needle (e.g., by means of a syringe). This package allows the integrity of the implant surface to be maintained.

[0072] Advantageously, the packaging is implemented such that the implant can be flushed with a liquid that dissolves the surface sealant. Thus, the packaging can be configured to allow this flushing while the implant remains covered by the packaging.

[0073] In contrast to existing solutions that rely on liquid substances in the implant container, the packaging according to the invention is configured to store the implant in a dry state, i.e., without using liquid or gel-like storage devices.

[0074] The implant kit of the present invention may further include a bag configured to receive the implant and a package for storage. The bag is preferably permeable to gaseous disinfectants and / or radiation-resistant. Therefore, the above-described disinfection steps can be implemented using this specially modified bag.

[0075] When using this type of bag, the implant kit is preferably packaged in another bag, seal, sheath, etc., after sterilization. This allows the contents of the permeable bag to be protected from, for example, moisture during sterilization and long-term storage.

[0076] In addition, the implant kit may include an insertion device for inserting the implant according to the invention into a lumen within the body, wherein the implant is disposed in or on the insertion device, as described above.

[0077] Another aspect of the invention relates to the use of the implant, as defined above, for the treatment of animals or humans. More specifically, this use includes dissolving a surface sealant covering at least a portion of the implant surface by rinsing the surface with a solvent or dissolving solution. For example, rinsing can be performed with water or an aqueous salt solution. Rinsing can be performed once the implant has been removed from its associated packaging and is ready for insertion. Further promotion or acceleration of the exposure of the implant surface to the lumen within the body can be achieved by performing additional optional rinsing operations, such as allowing a dissolving solution like water or sodium chloride solution to reach the implant through a catheter. Depending on the rinsing conditions, the dissolution of the surface sealant can also be substantially completed when the implant is inserted into the lumen within the body.

[0078] As described above, the solvent or dissolving solution can be delivered to the implant via an insertion device that communicates with the implant fluid. Therefore, the insertion device is preferably a catheter.

[0079] Preferably, the implant kit is implemented such that the implant is solublely bonded to the packaging. This bonding can be achieved by the manufacturing method described above. Bonding or merging the implant and packaging allows for effective protection of the implant surface, for example, by preventing friction between the packaging and the implant surface. When or shortly before implant insertion, it is preferable to flush the implant internally or via the packaging, causing the surface sealant to dissolve and the implant to be released from the packaging. Attached Figure Description

[0080] The implants and related implant kits and their uses according to the invention are described in more detail below with reference to exemplary embodiments and the accompanying drawings, in which:

[0081] Figure 1a A portion of the implant surface is schematically shown, ideally produced by a surface preparation and processing procedure designed to endow the target surface with characteristics that make the implant best suited for the intended treatment;

[0082] Figure 1b The diagram illustrates the onset of contamination on an implant surface that is not adequately isolated from the environment, and illustrates how an ideal implant surface can be rapidly lost by altering the initially desired performance.

[0083] Figure 1c A portion of the implant surface according to the invention is schematically shown, wherein a soluble surface sealant has been rapidly applied to protect the target properties conferred preventively to the implant surface;

[0084] Figure 1d The illustration schematically shows a portion of the implant surface where a soluble surface sealant has been applied and contaminated;

[0085] Figure 1eThis schematically illustrates the process when the implant is inserted into a lumen within the body. Figure 1d How the dissolution of the soluble surface sealant exposes the implant surface, which is in contact with... Figure 1a The surfaces obtained by preparation and treatment in the process are basically the same;

[0086] Figure 2 One possible embodiment of the implant kit according to the invention is shown in a specific case of a balloon-inflatable stent;

[0087] Figure 3 An embodiment of the application according to the invention is shown; and

[0088] Figure 4 This illustrates the common uses of the stent. Detailed Implementation

[0089] In the following description, certain terms are used for convenience and are not intended to limit the invention. The terms “right,” “left,” “up,” “down,” “below,” and “above” refer to directions in the figures. These terms include explicitly stated expressions and their derivatives and expressions with similar meanings. Furthermore, spatially relative terms such as “below,” “below,” “lower,” “above,” “upper,” “near,” and “far” may be used to describe the relationship between one element or feature and another element or feature as shown in the figures. These spatially relative terms are intended to cover different positions and orientations of the device in use or operation, in addition to those shown in the figures. For example, if the device in the figures is flipped, an element described as “below” or “below” other elements or features will become “above” or “above” other elements or features. Thus, the exemplary term “below” can cover both above and below positions and orientations. The device may be oriented in other ways (rotated 90 degrees or in other orientations), and the spatially relative descriptions used herein are interpreted accordingly. Similarly, descriptions of movement along and around various axes include various specific device positions and orientations.

[0090] To avoid repetition in the accompanying drawings and descriptions of various aspects and exemplary embodiments, it should be understood that many features are common to multiple aspects and embodiments. The omission of an aspect from the description or drawings does not mean that the aspect is missing from embodiments incorporating that aspect. Rather, the aspect may be omitted for clarity and to avoid lengthy descriptions. In this context, the following applies to the remainder of this specification: If, for clarity, the drawings contain reference numerals not set forth in the immediately relevant parts of the specification, reference to those reference numerals may be made in preceding or subsequent descriptive sections. Furthermore, for clarity, if reference numerals are not used for all features of a component in one drawing, reference is made to other drawings showing the same component. Similar reference numerals in two or more drawings denote the same or similar elements.

[0091] As mentioned above, considering the relevant influence of implant surfaces on key aspects of healing, such as thrombosis, inflammation, and proliferative responses, it has been found advantageous to preemptively impart certain target surface properties to implants prior to insertion. Indeed, contamination of implant surfaces by industrial impurities, unsuitable physical and chemical properties of these implant surfaces, or inappropriate distribution of electrostatic forces on these implant surfaces can lead to adverse protein interactions (e.g., proteins in blood and tissues of the body's luminal walls), uneven cell adhesion, and unpredictable healing patterns, ultimately affecting the outcome of the process.

[0092] In particular, the implant surface can be designed to incorporate antithrombotic properties that prevent thrombosis; and / or hydrophilicity and / or a given surface charge. Figure 1a An exemplary surface 10 of the implant 1 is shown, which is produced by a process that effectively imparts such target properties.

[0093] However, without properly preserving such target characteristics, the implant surface 10 may be rapidly and adversely affected, and the surface properties of the preventative design may be impacted by environmental contaminants, such as hydrocarbon deposits or other undesirable organic deposits 11, processing impurities 12, fibers, dust, etc. For example, this can lead to a loss of surface hydrophilicity. Furthermore, the implant surface may not be able to selectively modulate protein deposits, thus failing to prevent the adhesion of unwanted proteins and / or proteins in undesirable states—e.g., denaturation 13. This in… Figure 1b Examples are provided below.

[0094] exist Figure 1c The image shows a portion of the surface 10 of the implant, arranged to contact the wall of a lumen within the body and / or bodily fluids flowing through it. Surface 10 is covered with a protective surface seal 2 according to the invention. Figure 1dAs can be seen, the surface sealant may also be contaminated. However, potential contaminants are confined to the surface of the sealant and cannot reach the protected surface. The solubility of the sealant 2 when the implant 1 is implanted into the lumen is designed such that the surface 10 is exposed to the lumen and all necessary interactions between the body fluids and / or the lumen wall on the one hand and the implant surface 10 on the other hand occur effectively as intended—consistent with the target properties provided for the retention of the surface 10. After the sealant dissolves, Figure 1e The illustration shows a perfectly preserved surface 10, thus contaminants are removed along with the surface sealant. As explained in more detail above, the surface sealant 2 preferably comprises at least soluble carbohydrates or is composed of soluble carbohydrates. Trehalose has proven particularly suitable for forming the surface sealant 2.

[0095] The application of sealant 2 can be achieved by providing a sealant solution, i.e., a solution of the carbohydrate. The implant 1 can be coated by immersing at least a portion of the selected surface 10 in the sealant solution. Drying can then be performed to form the surface sealant 2.

[0096] exist Figure 2 The image shows an implant kit 100 according to the invention. Relative to the illustrated embodiment, the implant is a balloon-expandable stent 1, which is pressed onto a balloon 6 assembled on a catheter 3 for inserting and delivering the stent 1 to a desired location within the body lumen.

[0097] The implant kit 100 also includes a package 4 configured to protect the surface 10 of the stent 1. The package 4 is specifically designed to prevent damage to the surface 10 of the stent 1 from impact, other mechanical or thermal stress, scratches, and / or moisture. Because a seal 2 according to the invention is provided, and unlike prior art systems, no liquid or gel-like storage device is required, and the package 4 is configured to store the stent 1 in a dry state, this configuration is more practical, safer, space-saving, and economical than the configuration required for wet storage.

[0098] The pouch 5 can be disposed within the implant kit 100, configured to receive the stent 1, the associated package 4, and in this case, also the catheter 3. Figure 2 In one embodiment, the components of the stent 1, catheter 3, and packaging 4 are completely contained within the pouch 5.

[0099] The support 1 and other components of the kit 100 can be sterilized by applying radiation or gas after the step of covering at least a portion of the surface 10 with the surface sealant 2. Relative to Figure 2In this embodiment, disinfection can be achieved through the bag 5. In fact, the bag 5 and packaging 4 can be permeated with a gaseous disinfectant (such as ethylene oxide (ETO), etc.) and / or subjected to radiation disinfection, for example, through... or radiation.

[0100] The stent 1 can be used to treat animals or humans. The treatment procedure may include rinsing the surface 10 with a dissolving solution to dissolve the surface sealant 2. Figure 2 In this configuration, dissolution preferably occurs once the stent 1 has been removed from the pouch and packaging 4 and is ready for insertion. This flushing enhances the solubility of the sealant 2 and reduces the time interval before the inserted stent surface 10 is exposed to the body lumen or before the sealant is completely removed immediately before implantation. The dissolving solution can be delivered to the stent surface 10 via a catheter 3, which is in fluid communication with the stent 1. Alternatively, if the packaging 4 is implemented with an opening covered by a cap, the cap can be equipped with a diaphragm or similar structure that can be punctured to provide solvent to the stent 1.

[0101] exist Figure 3 The image shows the use of a stent 19 for implantation in the human body. In the first step 3A, the surface 109 of the stent 19 is hydrophilized and purified, so that the stent surface 109 is obtained in a highly purified state, which has target properties that are beneficial for implantation into blood vessels as lumens in the body.

[0102] Then, in the second step 3B, which is an embodiment of the manufacturing method according to the invention, a solution of sealant is provided, the stent 19 is immersed in the solution, and the sealant is dried on at least a portion of the surface to form a layer of trehalose as a surface sealant 29 on the surface 109 of the stent 19. In this way, the surface 109 is covered by the surface sealant 29 to protect the target properties, and this is an embodiment of the implant according to the invention.

[0103] In step 3C, the storage holder 19 is used. Over time, naturally occurring final contaminants 119 are collected and adhere to the surface sealant 29 of the holder 19. These naturally occurring contaminants 119 may include, for example, hydrocarbons from the atmosphere.

[0104] Later, for example, stent 19 is implanted into a blood vessel using a catheter. When stent 19 is inserted into the body, in step 3D, it is flushed with a saline solution. This dissolves and washes away the surface sealant 29 along with contaminants 119. After flushing, the stent surface 109 is once again in a highly purified state with the desired properties. Thus, stent 19 is inserted into the lumen of the body at its target location.

[0105] In step 3E, the stent 19 is positioned in its target location within the blood vessel. Since the stent surface 109 is essentially free of contaminants 119, the desired proteins 129 accumulate on the stent surface 109 of the implanted stent 19.

[0106] and Figure 3 Compared to the use of, Figure 4 The conventional use of the stent 19 for implantation in the human body is illustrated. In the first step 4A, the surface 109 of the stent 19 is hydrophilized and purified to obtain a highly purified stent surface 109 with target properties that are beneficial for implantation into blood vessels as lumens in the body.

[0107] In step 4B, storage holder 19 is used. Over time, naturally occurring final contaminants 119 are collected and adhere to the surface 109 of holder 19.

[0108] Subsequently, stent 19 is implanted into a blood vessel. When stent 19 is inserted into the body, it is rinsed with a saline solution in step 4C. After rinsing, the stent surface 109 is still at least partially covered by contaminants 119. In this state, stent 19 is inserted into the blood vessel at its target location.

[0109] In step 4D, the stent 19 is positioned in its target location within the blood vessel. Because the stent surface 109 contains contaminants 119, undesirable proteins 139, such as denatured proteins, accumulate on the stent surface 109 of the implanted stent 19.

[0110] This specification and the accompanying drawings illustrating aspects and embodiments of the invention should not be construed as limiting the scope of the claims defining the protected invention. In other words, while the invention has been shown and described in detail in the accompanying drawings and the foregoing description, such illustrations and descriptions should be considered illustrative or exemplary rather than restrictive. Various mechanical, compositional, structural, electrical, and operational changes can be made without departing from the spirit and scope of this specification and claims. In some cases, well-known circuits, structures, and techniques have not been shown in detail to avoid obscuring the invention. Therefore, it should be understood that those skilled in the art can make changes and modifications within the scope and spirit of the following claims. In particular, the invention covers other embodiments having any combination of features of the different embodiments described above and below.

[0111] This invention also encompasses all other features shown in the accompanying drawings, although they may not be individually described in the preceding or following description. Furthermore, a single alternative to the embodiments described in the drawings and specification, and a single alternative to their features, may be omitted from the subject matter of this invention or from the disclosed subject matter. This disclosure includes a subject matter consisting of features defined in the claims or exemplary embodiments, and a subject matter including said features. Furthermore, in the claims, the term “comprising” does not exclude other elements or steps, and the indefinite articles “a” or “an” do not exclude a plurality. A single unit or step may perform the function of multiple features recited in the claims. The mere fact that specific measures are recited in mutually different dependent claims does not imply that a combination of these measures cannot be used advantageously. The terms “substantially,” “about,” “approximately,” etc., combined with qualifiers or values, also specifically and explicitly define the qualifier or the value, respectively. The term “about” in the context of a given numerical value or range refers to a value or range, for example, within 20%, 10%, 5%, or 2%. Components described as connected or linked may be electrically or mechanically directly connected, or they may be indirectly connected via one or more intermediate components. No reference numerals in the claims should be construed as limiting the scope of protection.

Claims

1. An implant for insertion into a lumen within the body (1; 19）， The implant includes a surface (10; 109) at least a portion of which is arranged to contact the wall of the in vivo lumen and / or bodily fluids flowing therethrough when the implant (1; 19) is inserted into the in vivo lumen. Its features are, At least a portion of the surface (10; 109) is covered with a surface sealant (2; 29), which can be applied to the implant (1; 19) Dissolves upon insertion into the in vivo lumen, such that at least a portion of the surface (10; 109) is exposed to the in vivo lumen.

2. The implant (1; 19) according to claim 1, wherein, The surface sealant (2; 29) is designed to dissolve within 30 seconds.

3. The implant (1; 19) according to claim 1 or 2, wherein, The surface sealant (2; 29) comprises soluble carbohydrates, soluble polymers, soluble ionic compounds or combinations thereof, or is composed of soluble carbohydrates, soluble polymers, soluble ionic compounds or combinations thereof.

4. The implant (1; 19) according to claim 3, wherein, The soluble carbohydrate is a monosaccharide or sugar alcohol, such as threitol, erythritol, glucose, fructose, sorbitol, galactose, galactitol, mannose, mannitol, xylitol, inositol or similar, organic acid, such as citric acid, or other substances, such as vitamin C.

5. The implant (1; 19) according to claim 3, wherein, The soluble carbohydrate is a disaccharide or trisaccharide, such as trehalose, maltotriose, lactose, lactulose, palaginose, sucrose, or the like.

6. The implant (1; 19) according to claim 3, wherein, The surface sealant (2; 29) comprises a synthetic compound made of monosaccharides and / or disaccharides and / or trisaccharides and / or polymeric sugars.

7. The implant (1; 19) according to any one of the preceding claims, wherein, At least a portion of the surface (10; 109) is a flat surface, which preferably lacks significant waviness or roughness of its topology, or any significant texture, or coating, or a combination thereof.

8. The implant (1; 19) according to any one of the preceding claims, wherein, At least a portion of the surface (10; 109) is made of metal or metal alloy, or polymer, or ceramic material, or a combination thereof.

9. The implant (1; 19) according to any one of the preceding claims, wherein the implant is a vascular stent; or a drainage device; or an ophthalmic stent; or a coil or mesh structure for treating vascular aneurysms; or a heart valve; or a heart valve retainer; or a component of a cardiac pacemaker, such as an electrode; or a shunt.

10. The implant (1; 19) according to any one of the preceding claims, wherein, At least a portion of the surface (10; 109) is provided with the target property, preferably hydrophilic.

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