Antibiotic-loaded cartridge and prosthetic device with such antibiotic-loaded cartridge

Abstract

Antibiotic-loaded and preformed cartridge (100), prosthetic device (1) suitable for implantation in a bone or joint site of the human body, including a prosthetic body (2) equipped with a cavity or seat suitable for housing the cartridge (100); kit and method for obtaining it.

Description

[0001] "ANTIBIOTIC-LOADED CARTRIDGE AND PROSTHETIC DEVICE WITH SUCH ANTIBIOTIC-LOADED CARTRIDGE"

[0002] Designated inventors: Giovanni Faccioli; Renzo Soffiatti

[0003] TECHNICAL FIELD OF INVENTION

[0004] The present invention refers to an antibiotic-loaded cartridge for a prosthetic device capable of being implanted in a bone or joint of the human body, as well as such a prosthetic device equipped with an antibiotic-loaded cartridge.

[0005] In particular, this prosthetic device is able to elute or diffuse an antibiotic substance derived from that cartridge in order to prevent the onset of an infection or heal an ongoing infection.

[0006] STATE OF THE ART ANTERIOR

[0007] Statistically, it is known that a percentage of implants implanted inside the human body is prone to infection.

[0008] When this happens, the infected prosthesis must be removed from the implant site and, before a new prosthesis is implanted, the infection must be eradicated.

[0009] During this phase, spacer devices are usually used in order to maintain the conformation of the bone or joint site in which the new prosthesis will be implanted, while releasing substances capable of healing the infection.

[0010] This procedure is known as a "two-step treatment" for the removal of an infected prosthesis and the implantation of a new prosthesis.

[0011] Sometimes, however, when the bone conditions allow it, the surgeon chooses not to perform this procedure in two stages, but to apply a one-stage treatment according to which, after removing the infected prosthesis and "cleaning" the surgical site, the new prosthesis is immediately inserted into the implant site without first using a spacer device to treat the infection.

[0012] In this case, the new prosthesis can be fixed to the patient's bone with bone cement, such as antibiotic-loaded bone cement, or it can also be simply inserted into the bone, depending on the specific situation.

[0013] When the prosthesis is inserted into the bone without the use of bone cement, it is more easily removed in the event of a new infection. Of course, if the bone condition is very compromised, the use of bone cement to fix the new prosthesis is basically necessary.

[0014] Surgeons who decide to use "one stage" therapy rely on the fact that bone cleaning or remediation and systemic antibiotic therapy are sufficient to treat the current infection or to avoid the onset of a new infection. However, studies have shown that in this case, albeit in a small percentage, reinfection can occur, unlike what happens with two-phase treatment, in which the onset of a new infection is an extremely rare event.

[0015] There are gels, or similar substances, available on the market that can be applied, for example by brushing them, to the external surface of a prosthesis before implanting it. This procedure can be applied both to first insertion prostheses and to revision prostheses, i.e. implanted following the explantation of a first insertion prosthesis.

[0016] These gels or substances, however, although they are loaded with antibiotics, are ineffective against bacteria as the contact time with them is too short to be able to eradicate them. These substances, in fact, are mostly used to prevent microorganisms or bacteria, for example present in the external environment, from being present or installing themselves on the external surface of the prosthesis, thus preventing them from entering the surgical site; however, as mentioned, they are not specifically able to eliminate the bacteria present on site within the bone or joint site of implantation.

[0017] Patent application No JP2009298699 describes a porous capsule containing an antibacterial drug that is capable of releasing the drug slowly and that is capable of containing a high amount of antibacterial (although it is not specified what the order of magnitude of the amount of drug contained in the capsule is). The capsule is attached to a joint prosthesis in order to prevent infection.

[0018] Patent No. US8292967 describes a prosthesis including a porous insert selectively coupled toa surface of the prosthesis itself. The porous insert is intended to facilitate tissue growth and may include an antibiotic.

[0019] Patent application no. CA2734253 describes an orthopaedic implant equipped with an insert with a reservoir suitable for receiving at leastone medical substance. There are also openings to convey the medical substance from the tank to the treatment site.

[0020] At the end, patent no. US 11051945 describes a prosthetic implant equipped with a cavity filled with a filling material if desired including an antibiotic.

[0021] Therefore, the need for the surgeon to be able to implant prosthetic devices, both first implant and revision, capable of avoiding the onset of infections or able to heal those present, is increasingly felt.

[0022] AIMS OF THE INVENTION

[0023] The task of the present invention is to improve the state of the previous technology.

[0024] In the context of this technical task, it is the purpose of the present invention to provide a cartridge for a prosthetic device capable of preventing the onset of infections and capable of treating those present at the surgical site where the prosthetic device itself is implanted. Another purpose of the present invention is to provide an antibiotic-loaded cartridge that is preformed and has a porosity capable of guaranteeing the necessary release of antibiotics for the treatment of the affected surgical site.

[0025] An even further purpose of the present invention is to provide a cartridge that is loaded with at least one antibiotic, selected by the surgeon, based on the real needs of the patient. Another purpose of the present invention is to provide both a first implant and revision prosthetic device equipped with an antibiotic-loaded cartridge.

[0026] A further purpose of the present invention is to provide a prosthetic device with mechanical properties comparable to those of traditional definitive prostheses and able to heal or prevent an infection at the implant site.

[0027] In accordance with one aspect of the present invention, an antibiotic-loaded cartridge and a prosthetic device are provided in accordance with the attached independent claims.

[0028] In accordance with another aspect of the present invention, a kit and a method are provided according to the attached independent claims.

[0029] Dependent claims refer to preferred and advantageous forms of invention.

[0030] BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Further features and advantages of the present invention will be more evident from the detailed description of a preferred, but not exclusive, form of execution of a prosthetic device, illustrated by way of indication, but not limited to, in the attached tables of drawings in which:

[0032] Figure l is a side view of a portion or version of the prosthetic device according to the present invention in a disassembled version;

[0033] Figure 2 is a side view of a portion or version of the prosthetic device according to the present invention in a partially assembled version;

[0034] Figure 3 is a lateral cross-sectional view of a portion or version of the prosthetic device according to the present invention;

[0035] Figure 4 is a side view of a version of the prosthetic device according to the present invention, of a portion of it and of an antibiotic-loaded cartridge, respectively;

[0036] Figures 5A, 5B and 5C are lateral cross-sectional views of three versions of the prosthetic device portion according to the present invention;

[0037] Figure 6 is a perspective view of a further version of a portion of a prosthetic device according to the present invention;

[0038] Figure 7 is a side view of the portion of the prosthetic device in Figure 6;

[0039] Figure 8 is a side view of another portion of a prosthetic device according to the present invention;

[0040] Figure 9 is a perspective view of the portion of the prosthetic device in Figure 8; figures 10 A, 10B and 10C are lateral cross-section views of a further version of a portion of a prosthetic device according to the present invention; figures 11 A and 1 IB are respectively a perspective view and a cross-section view of yet another version of a portion of a prosthetic device according to the present invention; figures 12A and 12B are respectively a perspective view and a cross-section view of yet another version of a portion of a prosthetic device according to the present invention;

[0041] Figure 13 is a perspective view of another version of a portion of the prosthetic device according to the present invention;

[0042] Figures 14A and 14B are two perspective views of an area or tip of the prosthetic device in Figure 13;

[0043] Figures 15A and 15B are two perspective cross-section views of the area or tip of the prosthetic device of Figure 13,

[0044] Figure 16 is a SEM image of a matrix of PMMA-based antibiotic-loaded bone cement (indicated by BC) also containing barium sulphate (indicated by AR and surrounded by a peripheral reference line highlighting the granules or agglomerates of this salt), according to a version of the present invention,

[0045] Figure 17 is an enlarged detail of Figure 1, and

[0046] Figures 18A and 18B illustrate a laboratory test representing the device including the antibiotic-loaded cartridge according to the present invention immersed in a gelatin bath in order to highlight the leakage of the antibiotic AB from the inside to the outside through the openings or holes 7 in a first step (fig. 18A) and in a second time (e.g. after a few hours, fig. 8B), in the latter it is evident that the antibiotic that has come out is completely saturating all the available liquid of the gelatin bath (in fact, the liquid of the gelatin bath is cloudy due to the presence of antibiotic AB).

[0047] EMBODIMENTS OF THE INVENTION

[0048] With reference to the attached figures, a prosthetic device according to the present invention is indicated overall with 1.

[0049] That prosthetic device 1 comprises a permanent prosthesis, whether a first implant or a so-called revision prosthesis, i.e. inserted following the implantation of a spacer device in a two-stage treatment procedure or following the removal of a first prosthesis.

[0050] Prosthetic device 1 can be considered a device capable of combining the functionalities of a definitive “permanent” prosthesis and those of a "temporary" spacer device, as it performs the healing functions of the actual temporary spacer and, at the same time, acts as a permanent prosthesis for the patient.

[0051] Prosthetic device 1 can be a hip prosthesis (such as, for example, the portions illustrated in Figures 1 to 5C and 11A to 15B), a shoulder prosthesis, an elbow prosthesis, a knee prosthesis (such as, for example, the tibial portions illustrated in Figures 6 and 7 and / or the femoral portions illustrated in Figures 8 and 9), an acetabular cup (e.g. shown in figures 10A to IOC) or a bone prosthesis in general.

[0052] Prosthetic device 1 includes a prosthetic body 2.

[0053] The prosthetic body 2 includes, in a version of the invention, at least one tubular wall or stem 2a that defines an external surface 21, suitable for use to be faced or to come into contact with a patient's bone.

[0054] The tubular wall extends substantially along a longitudinal (Y) axis, in use arranged in a vertical direction from the upper to the lower part of the human body. The tubular wall can also define an internal surface 22, delimiting at least one internal cavity 5, arranged substantially along the longitudinal axis Y.

[0055] In an alternative version, prosthetic body 2 may comprise, in addition to or as an alternative to internal cavity 5, at least one housing seat 59 for at least one antibiotic- loaded cartridge 100.

[0056] The prosthetic body 2 also has a series of openings or holes 7 that fluidly connect the internal cavity 5 with the external surface 21, and / or the internal surface 22 with the external surface 21.

[0057] In addition, the dimensions of such openings or holes 7 will be proportional to the size of the device in which they are made. Therefore, a large device will have larger openings or holes 7 than those of a small device.

[0058] These openings or holes 7 have a cross-section, preferably circular or elliptical or slotshaped.

[0059] According to an embodiment, such openings or holes 7 have a straight pattern and / or a diameter (or larger size) of between 0,5 mm and 6 mm or from 0,5 mm to 4 mm or from 1 mm to 3 mm or from 1,5 mm to 3 mm or from 0,5 mm to 10 mm or up to 12 mm or 15 mm or up to 20 mm, depending on the location and size of the device where such openings or holes 7 are present.

[0060] By rectilinear course we mean that they can have a course perpendicular to the longitudinal axis Y.

[0061] As far as these openings or holes are concerned, their sizes may depend on the technique in which they are made, e.g. metal manufacturing technology or CNC technology. In particular, they must be small enough to be made with such techniques, at least according to the version of the invention in which they are used.

[0062] The dimensions of the openings or holes 7 are such as to allow the passage, in both directions, of liquids or gases, e.g. biological liquids, medicated substances, etc. These openings or holes 7 are, according to one version of the invention, evenly distributed along the entire wall and / or the external surface 21 of the prosthetic device 1. The openings or holes 7 are generally formed transversely with respect to the wall of the prosthetic body 2, so as to extend from the internal surface 22 to the external surface 21 of the same, and / or from the internal cavity 5 to the external surface 21.

[0063] In detail, these openings or holes 7 are passing between the internal cavity 5 and the space outside the prosthetic device 1 and therefore they are passing through the wall of the prosthetic device 1.

[0064] According to one version of the invention, e.g. illustrated in the enlarged detail of figure 17, openings or holes 7 may include either holes of circular cross-section, e.g. indicated by reference 7a, or openings of substantially elliptical or slotted section 7b, of elongated conformation, e.g. along a direction parallel to the longitudinal axis Y.

[0065] As you can see from the image, the overall size of the holes 7a is smaller than that of the openings7b. In particular, such openings may also have a size of approximately 6 mm by 12 mm or 4 mm by 12 mm or between 0.5 mm to 10 mm for the side or smaller size and from 3 mm to 15 mm or from 3 mm to 20 mm or from 6 mm to 20 mm or greater, for larger side or size.

[0066] Preferably, openings7b, when present, have a size of 4 mm by 12 mm or 6 mm by 12 mm for a medium-sized stem.

[0067] According to one version of the invention, these openings 7b are of the through type but their light is not "open" but occupied by an irregular mesh or cell or honeycomb texture, thus capable of passing biological liquids through canaliculi formed between the cells or in the mesh structure itself. In this way, however, the at least one channel or passage for biological liquids is smaller in size than the total size of the openings 7b themselves.

[0068] According to the present invention, there is an antibiotic-loaded cartridge 100. It is an element capable of releasing at least one antibiotic with a preformed conformation. This conformation can be substantially cylindrical, spherical, parallelepiped, prismatic, frustum of cone, frustum of pyramid, or in general having a three-dimensional conformation with a regular or irregular solid.

[0069] The term "cartridge" in this description refers to a solid and preformed element, having the above-mentioned conformation and with smaller dimensions than those of the prosthetic body 2 at which it is suitable to be housed / positioned.

[0070] The cartridge 100, in fact, can be housed in the internal cavity 5 and / or in at least one housing seat 59 present in the prosthetic body 2.

[0071] The cartridge 100, therefore, has a shape corresponding to that of the internal cavity 5 and / or of at least one housing seat 59.

[0072] The cartridge 100 is made of a porous material, i.e. it has a plurality of interconnected pores. These interconnected pores have an average diameter of 0.1 microns to 0.5 cm or 0.1 microns to 1 mm or 0.1 microns to 0.1 mm or 0.1 microns to 300 microns or 1 microns to 100 microns.

[0073] The cartridgelOO, in a version of the invention, is made of bone cement (BC). Such a material is a permanent material, i.e. not resorbable or degradable, once implanted in the human body.

[0074] Usually, traditional bone cement releases very little antibiotic, in an insignificant amount for the purposes of an effective antibacterial or anti-infective action.

[0075] Furthermore, since the internal cavity 5 and / or at least one housing seat 59 can be "small" compared to the volume of the prosthetic body 2, the volume of the cartridge can also be "small" and consequently the amount of antibiotic contained in it may not be very high, indeed it could be a few grams.

[0076] For example, in order to be effective, the amount of antibiotic released by the cartridge 100 should be at least equal to that released by a temporary spacer made entirely of antibiotic-loaded bone cement (which can reach a weight of about 100 grams and more). In order to obtain a high release of antibiotic, so as to be able to carry out its function of prevention and / or healing of the infection, it was therefore necessary to increase the amount of antibiotic contained in the cartridge itself. At the same time, however, it is necessary to avoid having short and violent releases, which could be toxic to the patient and which could occur in the presence of high quantities of antibiotic substance.

[0077] To this end, therefore, it has been seen that thanks to the cartridgelOO, despite the relatively high quantities of antibiotics present, it is possible to obtain a predetermined, locally effective release (also thanks to the specific sizes of the cartridgelOO) which completely avoids the risk of toxicity for the patient, as the release occurs gradually over time and the quantity released never reaches dangerous values for the patient.

[0078] In traditional antibiotic-loaded bone cements and known spacers, the percentage of antibiotic is around 5%. The cartridgelOO, on the other hand, by virtue of its reduced volume with a weight of a few grams, contains a percentage of antibiotic varying between 20% and 70% by weight compared to the total weight of the cartridge, preferably between 30% and 70% or between 40% and 60% or between 50% and 70%; the remainder is the material that makes up the cartridge and preferably is bone cement (PMMA). As a result, the less PMMA the cartridge makes, the more porous it is.

[0079] According to at least one version of the present invention, such a small amount of bone cement (PMMA) in order to be able to compact such high quantities of antibiotic, requires different polymerization conditions from those used with traditional bone cement, i.e. by controlled temperature, pressure and time. This makes the cartridges 100 qualitatively repeatable.

[0080] Porosity also varies by varying the cartridge forming pressure. For example, the higher the pressure, the lower the resulting porosity and vice versa.

[0081] For example, the material obtained at very low pressure favors the production of extreme porosity. On the other hand, by injecting the same material into a mold by means of a high-pressure press, a completely porosity-free product is obtained. For example, pressures of 50 Bar or 100 Bar, or 725 psi or 1450 psi, ensure no internal cavities or canaliculi. Pressures below 10 Bar or 145 psi, up to moderate vacuum values of 0.5 Bar or 7.25 psi, allow the presence of air or other gases bubbles, resulting in variable porosity in the material.

[0082] For this reason, the porosity of the cartridge 100 is increased compared to the intrinsic porosity that is formed by the polymerization of traditional bone cement and also increased compared to that of a temporary spacer device of a known type.

[0083] This porosity, in particular, is achieved by the high percentage of salts (the antibiotic itself is a salt that does not bind with the liquid monomer and therefore is not sealed during polymerization) and the low percentage of bone cement (PMMA) give it a natural porosity. The reactive conditions mentioned above (pressure, temperature and time) confer repeatability of porosity and therefore pre-established release conditions to be effective.

[0084] The antibiotic (AB) present in the cartridge 100 can be present in the form of a very fine powder of a few microns in size, or in the form of beads or spherules or granules ranging in size from 100 microns to 500 microns or 0.5 mm or up to 5 mm.

[0085] In this way, for example, the mass (of a few grams) of bone cement of the cartridge 100 will be able to release the same amount of antibiotic that would be released by a temporary spacer device of more than 100 grams and / or a mass of traditional bone cement of more than 100 grams.

[0086] Equally important is the way in which the bone cement is placed in the internal cavity 5 and / or in the housing seats 59. According to the present invention, in fact, it is not possible to inject the antibiotic-loaded bone cement in the fluid state into the internal cavity 5 and / or into at least one housing seat 59 and wait for it to polymerize.

[0087] In fact, the injection of cement would fill the internal cavity and / or at least one housing seat 59 but would also seal all openings or holes 7 present in the prosthetic device 1. In fact, in such a situation, only the external surface of those openings or holes 7 would constitute the interface for the exchange of antibiotics, but its extension would be very low and therefore ineffective for the purposes intended.

[0088] In fact, the cartridge 100 of the present invention is precisely loaded with the desired amount of antibiotic directly from the manufacturer. It is in fact an antibiotic-loaded and preformed cartridge (i.e. already solidified). Once this preformed cartridge has been obtained, it is inserted inside the internal cavity 5 and / or positioned inside at least one housing seat 59. Since the cartridge 100 is placed already preformed, the openings or holes 7 remain accessible or empty and can therefore allow the entry of biological fluids suitable for reaching the cartridge 100 and determining the elution of the antibiotic contained in it.

[0089] As can be seen from figure 3, the internal cavity 5 has a slightly larger size than that of the cartridge 100. This determines the presence of an empty gap 70 inside the internal cavity 5 which allows the transit of biological fluids, which are able to reach the entire external surface 101 of the cartridge 100 and determine the elution of antibiotic contained in it.

[0090] Figures 5A-5C illustrate some examples of antibiotics present in cartridge 100. In particular, Figure 5 A shows a cartridge 100 containing only one antibiotic A, such as gentamicin, Figure 5B shows a cartridge 100 containing an antibiotic A, such as gentamicin, and an antibiotic B, such as vancomycin, mixed together, and at the end Figure 5C shows a cartridge 100 in which two antibiotics A and B are both present but separate from each other, for example, antibiotic A or gentamicin at the top and antibiotic B at the bottom or vice versa.

[0091] Therefore, the antibiotic contained in cartridge 100 can be gentamicin and / or vancomycin or another antibiotic suitable for this purpose.

[0092] In this form, there may be a single cartridge equipped with the two portions loaded with the two different antibiotics or there may be several cartridges, of shorter length, each loaded with a single antibiotic, different from that contained in another cartridge positioned in the same internal cavity 5.

[0093] This option avoids mixing and contact between the two antibiotics A, B, avoiding the risk of damage to the individual molecules. The contact between the two antibiotics, in fact, is not potential but real, given the high concentration of each of the two. In fact, for example, gentamicin is a sulfate while vancomycin is a hydrochloride, therefore two different salts that are potentially reactive and therefore unstable.

[0094] The same solution can also be applied in the presence of more antibiotics than the two indicated above or with different pairs of antibiotics.

[0095] In all examples, it is understood that the cartridge 100 includes the material that constitutes it (such as the cement mass) containing the powder (or granules) of at least one selected antibiotic.

[0096] In figures 1 to 5C, the prosthetic device 1 according to the present invention includes, as prosthetic body 2, a stem component 2a of a hip prosthesis.

[0097] In this case, the hip prosthetic device may include a head component 26, intended to be connected to the stem component 2a, and suitable in use to articulate at the acetabular joint of the hip itself.

[0098] The stem component 2a has an elongated shaft-like conformation along the longitudinal axis Y, and has a first proximal end 23, as well as a second distal end 24, the latter suitable for being inserted, during use, deep into the medullary canal of a patient's bone (e.g. femoral).

[0099] The first proximal end 23 ends with a neck portion 25, suitable in use to be connected to the head portion 26.

[0100] The internal cavity 5 is determined within the stem component 2a so as to present a substantially elongated conformation along the direction of the longitudinal axis Y of the stem component 2a, from its first end 23 to its second end 24.

[0101] In a version of the invention, the stem component 2a can have a tapered shape from the first end 23 to the second end 24.

[0102] The dimensions of the internal cavity 5 may have a range of different sections than the overall dimensions of the prosthetic device 1. This is because the prosthetic component must be able to withstand mechanical stress in order to meet the requirements of the reference standards. The diameter of the inner section is consequently dependent on the total dimensions of the prosthetic device. According to a non-limiting example, the dimensions of the internal cavity 5 are reduced compared to the overall dimensions of the prosthetic device 1, so as not to reduce or affect the mechanical properties of the prosthetic device 1 according to the present invention.

[0103] For example, the dimensions of the internal cavity 5 may have a size (corresponding to the diameter or at least one side or cross-sectional size) from 1 to 10 mm, or from 1 to 5 mm or 6 mm. In particular, the size of the cross-section of the internal cavity 5, in at least one version of the invention, corresponds to the sizes of the insertion opening 10, as better specified below.

[0104] For example, when the outer diameter of the stem is really large, i.e. in the range of 30- 40 mm, the 10 mm diameter inner cavity is not excessive.

[0105] The prosthetic device, in fact, can be positioned, in use, within a bone or joint site and must be able to support the patient's weight and / or movements related to the area in which it is implanted.

[0106] Compared to a completely full prosthetic device, for example a traditional prosthesis, therefore, the presence of the internal cavity 5 must not compromise the mechanical properties of the prosthetic device itself.

[0107] The internal cavity 5, as anticipated, is suitable for housing the cartridge 100. However, the wall of the inner cavity 5 does not join the cartridge material 100 and, even if there is contact between them, they remain two separate and independent entities.

[0108] According to one version of the present invention, the length of the cartridge 100 corresponds to the length of the inner cavity 5 and the diameter (or cross-section) of the cavity 5 is slightly greater than or equal to the diameter (or cross-section) of the cartridge 100. In this way, a uniform release of antibiotic is ensured along the entire external surface 21, through the openings or holes 7.

[0109] The material of the cartridge 100, however, never occupies the space defined by the openings or holes 7, as it must remain accessible to allow the passage of fluids.

[0110] In one version of the invention, the material of the cartridge 100 includes at least one of the following materials: acrylic resin, composite material comprising calcium phosphate or an inorganic salt, calcium sulfate, bioglass, polyvinyl alcohol, a mixture thereof. Preferably, the material of the cartridge 100 consists of a PMMA-based BC bone cement. In a further version, the material of the cartridge 100 includes a composite material consisting of an acrylic resin and an inorganic salt, such as PMMA (polymethyl methacrylate) and calcium phosphate or tri-calcium phosphate (TCP).

[0111] The material of the cartridge 100, in at least one version of the present invention, can have capillary capacity, i.e. it includes, substantially for its entire volume, interconnected canaliculi with micrometric transverse dimensions (i.e. considering the size perpendicular to the dimension of greatest extension of the canaliculus itself), capable of absorbing and eluting liquids by capillarity. The average cross-sectional diameter of such canaliculi is generally less than 100 microns or between 0.1 microns and 100 microns or between 0.1 microns and 300 microns.

[0112] In a further version of the invention, the material of the cartridge 100 may consist of a water-soluble material consisting of calcium salts, such as TCP, calcium sulfate, hydroxyapatite, calcium carbonate and mixtures between them. These products, in addition to being water-soluble, are prepared by combining a powder of calcium salts with an aqueous solution of phosphate buffer. This mixture hardens and can be preformed to form the cartridgelOO. Inside the hardened structure, however, water remains which is removed by evaporation, creating a network of capillaries or canaliculi, which determine the aforementioned capillary force.

[0113] In this way, the material that makes up the cartridge 100 is able to absorb an antibiotic aqueous solution and / or is able to allow its elution (even when the antibiotic is in powder form) thanks to the contact in use with the patient's biological fluids.

[0114] As mentioned above, the material of the cartridge 100 includes at least one antibiotic and, in order to effectively perform its infection curative or preventive function, the ratio of antibiotic to the remaining material must be carefully calibrated.

[0115] In practice, in the version in which the material that makes up the cartridge is a PMMA- based bone cement, the percentage of antibiotic will be higher than the percentage of PMMA, for example compared to traditional antibiotic-loaded-type bone cements, as indicated above.

[0116] In figure 3, at the second end 24, a closing and / or centering means 30 is visible, for example configured as a conical or prismatic tip. This closing and / or centering means 30 may have a double function, i.e. it acts as a closing cap of the internal cavity 5, to prevent the cartridge 100 from coming out of the cavity itself and instead remaining in position once inserted, but it can also act as a guide and centering of the second end 24 of the stem component 2a, which thus remains centered in the diaphyseal or medullary canal of the patient's bone.

[0117] According to a further version of the present invention, for example illustrated in figures 6 and 7, prosthetic device 1 comprises a prosthetic body 2 shaped like a tibial portion of a knee prosthesis.

[0118] This version has the same characteristics as the one just described, it varies only in shape, which is specific to the implantation site in which it is to be placed.

[0119] The prosthetic body 2 includes a tibial plateau 40 equipped with at least one wall, such a wall having an external surface 41, suitable during use to come into contact with the tibial bone of the knee joint, as well as an articulation surface 42, suitable during use to come into contact and articulate with the femoral bone of the knee joint or with a femoral prosthetic component. Prosthetic body 2 may also include a stem component 2b, suitable for insertion into the tibial medullary canal at the knee joint.

[0120] The stem component 2b has an internal cavity 5 and openings or holes 7, 7a, 7b, in the same way as the stem component 2a described above.

[0121] The stem component 2b can also have a tapered conformation along the longitudinal axis Y but, unlike the stem component 2a for the hip prosthetic device, it has neither a neck nor a head portion.

[0122] The stem component 2b rises from the tibial plateau 40, in particular from the external surface 41 of the same, and has an elongated shape with a first base end proximal to the tibial plateau 40 as well as a second distal end 24, the latter being able to be affected by the means 30.

[0123] The tibial plateau 40 includes at least one transverse internal cavity 51.

[0124] This transverse internal cavity 51 has an elongated course (similar to internal cavity 5) but instead of being arranged along the Y-axis, it lies along a transverse plane X, parallel to the transverse plane of the human body and / or perpendicular or transverse to the axis Y.

[0125] More specifically, the course of at least one transverse internal cavity 51 can be in the antero-frontal direction, and / or in the side-side direction or it can have a substantially radial trend, as for example illustrated in figure 6, or a combination of these arrangements. The tibial plateau 40 has a substantially box-like wall. In particular, it can include at least two portions or half-shells 40a, 40b (e.g. illustrated in figure 7) which, joined together at the transverse plane X.

[0126] The first portion or half-shell 40a and the second portion or half-shell 40b comprise the aforementioned wall which delimits the external surface 41, the articulation surface 42 and at least one transverse internal cavity 51.

[0127] Thus, at least one transverse internal cavity 51 is defined by both portions or half-shells 40a, 40b while in an alternative version at least one transverse internal cavity 51 can only be defined in one of these portions.

[0128] According to one version of the invention, at least one of the first portion or half-shell 40a and the second portion or half-shell 40b is hollow, i.e. it includes at least one internal space 71.

[0129] In the event that both portions or half-shells 40a, 40b are hollow, they are joined at their peripheral edges 44, which face each other, to form a complete prosthetic body 2.

[0130] The prosthetic device 1 according to the present invention, in a further version, includes a prosthetic body 2 shaped as a femoral component 60 of a knee prosthesis.

[0131] This femoral component 60 may be composed of a first portion or half-shell 60a (e.g. condylar) and a second portion or half-shell 60b (e.g. of articulation), at least one of which may be hollow.

[0132] In this case, the portions or half-shells 60a, 60b can be joined by means of their respective external peripheral edges, made in their lateral wall and facing each other, so as to constitute, once joined, the entire femoral component 60 of the prosthetic device according to the present invention.

[0133] In addition to or alternatively, the femoral component 60 defines an external surface 61, suitable in use to be placed at the femoral bone of the knee joint, and an articulation surface 62, suitable in use to articulate with the tibial bone of a patient at the knee joint or with the tibial component of a prosthesis or with the tibial plateau 40.

[0134] The femoral component 60 may also include a stem 2b, which is suitable for placement within the medullary canal of the femoral bone, at the knee joint, which is very similar to the stem component 2b described above.

[0135] Preferably, at least one transverse elongated cavity 51 of the femoral component 60 is arranged in a transverse or side-to-side direction with respect to the human body.

[0136] According to one version, it is possible that at least one internal cavity 5 is in fluid communication with at least one transverse internal cavity 51. In an alternative form, there is no fluid communication between such cavities.

[0137] The prosthetic device 1, with its prosthetic body 2, can be made of a biologically compatible material, of the type that can be implanted inside the human body, such as metal, e.g. steel or titanium, metal alloys, plastic or acrylic resins, polymeric materials, etc.

[0138] The material of prosthetic device 1, however, must be able to guarantee the necessary mechanical properties, e.g. weight support and / or wear resistance, suitable for performing the function of permanent bone prosthesis.

[0139] The prosthetic device 1, in a version of the invention, can be massive, and / or solid (with the exception of the internal cavity 5, the at least one transverse internal cavity 51 and any housing seats 59) and / or in a single piece, for example with no junction planes between its components, such as between stem 2a and neck portion 25 or between tibial plateau 40 and stem 2b or between femoral component 60 and stem 2b.

[0140] The cartridge 100 can include, in a version of the invention, in addition to at least one antibiotic, also at least one additional pharmaceutical or medical substance.

[0141] If the material of the cartridge 100 also includes calcium or other inorganic salts, such calcium or such salts or ions of the same may also be eluted or dispensed along with the dispensing of the antibiotic or pharmaceutical or medical substance.

[0142] These inorganic substances can be beneficial for the surrounding bone tissue with which they come into contact.

[0143] As mentioned, the prosthetic body 2, to be inserted at the hip joint, can also include a head component a 26, of a hemispherical conformation suitable for articulating with the cup or acetabulum of the hip.

[0144] This head component 26 may also include an internal cavity, with a conformation corresponding to that of the head, and therefore at least partially hemispherical, suitable for containing an antibiotic-loaded cartridge of the corresponding shape. In this case, the openings or holes 7 can be arranged radially to the head itself.

[0145] The head component 26 may also include, instead of the internal cavity described above, at least one transverse internal cavity, which is essentially cylindrical, e.g. from side to side or arranged in an anterior-posterior direction with respect to the human body, in order to accommodate at least one cartridge 100 of corresponding conformation.

[0146] Furthermore, the head component 26 may include, in addition or alternatively, at least one housing seat with a circumferential or annular arch shape, arranged at its articulation surface, in order to accommodate a cartridge with a corresponding shape.

[0147] In any case, the presence of at least one internal cavity and / or housing seat and / or at least one cartridge, together with the size of the openings or holes, are such as not to interfere with the rotation and / or articulation movement of the head itself in its joint area of implantation.

[0148] Figures 10A, 10B and IOC illustrate an acetabular version of the present invention, in which prosthetic device 1 includes a prosthetic body 2 shaped like an acetabulum or acetabular cup 50.

[0149] The acetabulum or acetabular cup p 50 has a dome or hemisphere conformation; it constitutes the upper part of a total hip prosthesis as, in use, it is inserted and / or fixed in the acetabular or cotyloid cavity, at the level of the patient's pelvis.

[0150] This version has the same characteristics as the one just described but varies in shape, which is specific to the implantation site in which it is to be placed.

[0151] The prosthetic body 2 includes at least one wall defining an external surface 57, suitable in use to contact with the acetabular bone, as well as an articulation surface 58, suitable for use to articulate with a femoral head or with a head component of a hip prosthesis.

[0152] In one version of the invention, the articulation surface 58 of the acetabulum or acetabular cup 50 is suitable for coupling to a joint insert 80, e.g. ceramic or polyethylene, interposed between the cup itself and the head of the femur or femoral component.

[0153] In the wall that constitutes the acetabulum or acetabular cup 50 there is at least one internal cavity 52, if desired of a substantially spherical or arched or elongated or annular shape, and a plurality of openings or holes 7.

[0154] Similarly, at least one cartridge 100, in this version, can have a substantially spherical or arched or elongated or annular conformation, so that it can be inserted and housed in the corresponding at least one internal cavity 52.

[0155] In this version, the openings or holes 7 may be present both at the wall of the acetabulum or acetabular cup 50, and at at least one internal cavity 52.

[0156] Outside the cup 50, at the bone tissue adjacent to at least one opening or microhole 7, an elution zone 7a of at least one antibiotic contained in cartridge 100 is delimited.

[0157] In one version of the invention, at least one internal cavity 52 is placed at the articulation surface 58 of the acetabulum or acetabular cup 50, while the openings or holes 7 are positioned at the outer surface 57, so as to elute the antibiotic in the direction of and / or in contact with the patient's bone.

[0158] In an alternative version, at least one internal cavity 52 is arranged at the central part of the thickness and / or wall of the acetabulum or acetabular cup 50, and the openings or holes 7 are positioned both at the external surface 57 and at the articulation surface 58, so as to allow homogeneous delivery on both sides of the prosthetic device.

[0159] If desired, the acetabulum or acetabular cup prosthetic component 50 can also consist of two portions or half-shells, in a similar way to what has been described above.

[0160] Figures 11A and 11B illustrate a further version of prosthetic device 1 according to the present invention (represented as stem 2a, although this embodiment can also be applied to any other prosthetic body described in this description) equipped with at least one housing seat 59 for at least one cartridge 100. In order to keep the cartridge 100 in position, its ability to be at least partially elastic and / or flexible (although not fragile but moderately tenacious and elastic) is exploited and, therefore, they are inserted into their respective housing seats and held in them by the provision of light undercuts, with which the cartridges "fit" exploiting their flexibility.

[0161] This at least one housing seat 59 is external, in the sense that it is positioned at the surface of the prosthetic body 2 suitable for coming into contact with and / or facing the patient's bone.

[0162] It is also possible that, in the same prosthetic device 1, there is at least one internal seat 5, 51, 52 and at least one housing seat 59. In addition, it is possible that only some or all of the internal seats 5, 51, 52 and only some or all of the housing seats 59 are occupied by a matching-shaped cartridge 100. At least one antibiotic contained in each cartridge 100 may be the same, different or mixed than at least one antibiotic contained in another cartridge in the same prosthetic device 1.

[0163] In the area of the prosthetic body 2 in which the housing seat 59 is made, the prosthetic body is full, in the sense that it is not a hollow component and the material that makes up the prosthetic body completely surrounds the area where the housing seat 59 is obtained. In fact, the housing seat 59 is hollowed out with respect to the external surface of the prosthetic body 2 and, when it houses the cartridge 100, together with the latter determines the creation of a substantially continuous and smooth external surface of the prosthetic device itself.

[0164] The shape of the cartridge 100 corresponds to and complements that of the housing seat 59 in which it is to be inserted. Also in this case, it is possible that a gap 70 may remain between the perimeter surface of the housing seat 59 and the cartridge 100, in order to allow an easier flow of the patient's biological fluids that determine the elution of the antibiotic and the performance of the healing and preventive functions of the prosthetic device 1.

[0165] In the illustrated embodiment, at least one cartridge 100 has a cylindrical shape and at least one housing seat 59 has a substantially corresponding conformation, having dimensions slightly larger than those of the cartridge itself.

[0166] For example, there may be several seats 59 (and consequently several cartridges 100) placed with their longer side arranged along the longitudinal axis Y and positioned offset from each other, both in height and width, with respect to the other seats present in the stem component 2a.

[0167] As you can see, the cross-section (width and thickness) of the housing seats 59 is much smaller than their length. In this way, it is possible to almost completely "restore" the external surface of the prosthetic device 1 thanks to the external surface 101 of the cartridge 100, which when the latter is inserted in seat 59, forms part of the external surface of the device itself.

[0168] Figures 12A and 12B illustrate a version corresponding to the one just described, but in this case the conformation of at least one housing seat 59 and at least one cartridge contained in it is substantially spheroidal.

[0169] A further version of the present invention is illustrated, for illustrative purposes only and not limitation, in figures 13 to 15B.

[0170] This version is illustrated as a hip prosthetic device but is also applicable to the devices described above suitable for implantation in different anatomical districts.

[0171] In particular, prosthetic body 2 has a series of grooves 90, which are recessed with respect to the external surface of prosthetic body 2. In the illustrated case of stem 2a, these grooves are longitudinal, i.e. they are parallel to the longitudinal axis Y.

[0172] The grooves 90 can have a width (transverse) of about 2 mm and a depth of about 1 mm or a size between 1 mm and 5 mm. The length of the grooves is substantially the same as that of the stem 2a, 2b. In the case of the tibial 40 and femoral 60 components, there may be grooves, not illustrated, for example arranged at their external surface 41 or 61. The arrangement of the grooves, in this case, can be parallel to the transverse plane of the human body, with a trend along the anterior-posterior or side-side direction, or even with a radial arrangement, evaluating, for example, the C-shaped conformation of the tibial plateau 40 illustrated in figure 6, considering as the center the central point of the concavity of the C (which in use is positioned at the back of the knee).

[0173] These grooves, in the case of stem 2a and tibial plateau 40, can be considered substantially straight.

[0174] They can also be present, in addition or alternatively, at the level of stem 2b, with an arrangement and conformation substantially similar to that just described.

[0175] In the case of the femoral component 60, on the other hand, given that the external surface 61 has a substantially arched course, with a concavity in use facing the patient's femoral bone, the grooves can have an arched course, along an anterior-posterior direction, or substantially straight, in a side-to-side direction.

[0176] What characterizes this version, however, is the positioning of the openings or holes 7 along these grooves. In this way, in fact, the openings or holes 7 are "spaced" by a distance D equal to the depth of the grooves, from the patient's bone and this allows them to be kept accessible and suitable for the transit or flow of biological fluids that go from the bone to the cartridge 100, in order to elute the antibiotic and / or other medical or pharmaceutical substances contained in it.

[0177] An aspect that characterizes the present invention in its various forms concerns the fact that the internal cavity 5 and / or the transverse internal cavities 51, 52 are equipped with at least one insertion opening 10, located at at least one area or portion of the external surface of the prosthetic body 2.

[0178] This insertion opening 10 allows the insertion of the cartridge 100 and therefore has slightly larger dimensions, for example compared to the diameter or cross-section of the latter, so as to allow it to be housed inside the cavity of interest.

[0179] In the case of stem 2a, 2b, this insertion opening 10 is placed at the second distal end 24. Therefore, when the means 30 are present, they are suitable for closing the insertion opening 10, so as to prevent the cartridge 100 from coming out.

[0180] As can be seen, for example, in Figures 3 and 5, stem 2a comprises, in the opposite position to the insertion opening 10, i.e. at the first end 23, a channel 12. This channel 12, having dimensions substantially corresponding to those of the openings or holes 7, can have the function of letting any air present inside the internal cavity 5 escape from stem 2a and / or to allow the biological fluids to reach the cartridge 100 even at this upper portion in use. Similarly, biological fluids can also escape through this channel 12, causing the antibiotic taken from cartridge 100 to be eluted at the end 23 and / or the neck portion 25 and / or the head component 26.

[0181] In a preferred version of the invention, the ends 23, 24 of stem 2a are affected respectively by channel 12 and by the insertion opening 10 while the substantially tubular side wall, arranged between these ends, is affected by openings or holes 7, which therefore have a substantially transverse and / or radial trend with respect to the longitudinal axis Y. The insertion opening 10 and channel 12, on the other hand, have a trend placed substantially at the longitudinal axis Y.

[0182] Considering the versions relating to the tibial component 40 and the femoral component 60, it can be seen that stem 2b lacks channel 12 but instead has the insertion opening 10 having substantially the same characteristics described above, also with regard to the possible arrangement of the openings or holes 7.

[0183] According to one version of the present invention, for example shown in Figure 14A, the insertion opening 10 has a substantially starry shape. The function of this conformation is to leave space available for biological fluids to wash the antibiotic out of the cartridge 100.

[0184] As can be seen from this embodiment, the (metal) wall that constitutes the stem 2a is thin, if compared with the transverse width of the internal cavity 5.

[0185] As can be seen from figures 15A and 15B, in the illustrated version the internal cavity 5 has a starry cross-section, conformed in a similar way to the shape of the insertion opening 10. In this way, the inner wall of the prosthetic body 2, at grooves 90, contacts or is proximal to surface 101 of cartridge 100. On the other hand, between one groove and another, longitudinal channels 14 are internally formed, which "expand" the internal space of cavity 5 and facilitate the flow of biological fluids that pervade the internal cavity itself.

[0186] The same can happen for stem 2b.

[0187] Alternatively, grooves 90 may be present externally and internally the internal cavity 5 may have a circular or prismatic section, corresponding to that of cartridge 100, without the formation of channels 14.

[0188] In the embodiment of the tibial component 40, the transverse internal cavities 51 are also each equipped with an insertion opening 10. The latter, therefore, is placed at the lateral wall that joins the external surface 41 and the articulation surface 42 and which constitutes the thickness of the tibial plateau 40.

[0189] In this embodiment, the openings or holes 7 are placed at the external surfaces 41 and the articulation surfaces 42, thus substantially perpendicular to the course of the transverse internal cavities 51.

[0190] Of course, the openings or holes 7 are placed at least at the cavities that fluidly connect with the external environment surrounding the prosthetic device 1.

[0191] In this version, moreover, the transverse internal cavities 51 are passing from side to side or in an anterior-posterior direction with respect to the tibial plateau 40. This means that these cavities have two insertion openings 10, one positioned on one side and the other on the other or one positioned in a frontal position and the other in a posterior position, considering the positioning of the tibial plateau 40 in use.

[0192] The surgeon, before implantation, can then decide from which opening 10 to proceed with the insertion of the cartridge 100.

[0193] In this case, no means are required to close the openings 10 present at the thickness of the tibial plateau, in a similar way to the means 30 that close the central cavity of the stem, as the position of the cartridge 100 is in this case horizontal and not vertical, therefore, the possible forces of gravity acting as extraction are modest. Therefore, they are held in place simply by interference with the cavity and especially by the peripheral tissues that act as a natural plug.

[0194] Similarly, considering the femoral component 60, the transverse internal cavities 51 can be through from side to side or from the frontal to the posterior area of the prosthetic component 1 considering its positioning in use. In this way, there are two insertion openings 10, in a way that corresponds entirely to what has just been described in relation to the tibial plateau 40.

[0195] As regards the version relating to the acetabulum or acetabular cup 50, in this case the insertion opening 10 is usually placed at the articulation surface 58 of the prosthetic body 2. In this case, the cartridges 100 are inserted from this articulation surface 58. If the cartridges have a substantially spherical shape, the insertion opening 10 has a substantially circular shape.

[0196] If, on the other hand, the internal cavities 52 of the acetabulum or acetabular cup 50 have an elongated conformation, they may have a substantially rectilinear course, for example passing from the external surface 57 to the articulation surface 58.

[0197] The acetabulum or acetabular cup 50, moreover, could also include, in addition or alternatively, housing seats 59 having a substantially annular or circumferential arc shape (capable of housing cartridges 100 of corresponding conformation), arranged along the external surface 57 and / or articulation surface 58 of the prosthetic body 2. In this case, the insertion openings may have an annular or arched shape.

[0198] In general, the housing seats 59 have an insertion opening 10 having a conformation substantially corresponding to the cross-section or longitudinal section of the cartridge 100 to be accommodated.

[0199] The present invention further refers to a kit including the prosthetic device 1 and at least one cartridge 100 described above. For example, there can be two cartridges, a first containing an antibiotic A and a second containing an antibiotic B, or at least two, at the discretion of the surgeon who can select the antibiotic or antibiotics that best suit the needs of the patient and the implantation site.

[0200] Finally, the present invention refers to a method for the realization of a prosthetic device 1 according to the present invention, comprising the steps of providing a prosthetic device 1, suitable for implantation in a bone or joint site of the human body, providing an antibiotic-loaded cartridge 100 and inserting the cartridge 100 into at least one internal cavity 5, 51, 52 and / or in a housing seat 59 of the prosthetic body 2, e.g. via an insertion opening 10. The method then comprises a step of closing the insertion opening 10 by means of closing and / or centering means 30.

[0201] The step of providing the prosthetic device 1 comprises, in a version of the invention, providing a first portion or half-shell and a second portion or half-shell and joining them together at their peripheral edge, the one facing towards the peripheral edge of the other. The joining of the first portion or half-shell to the second portion or half-shell can take place by welding or melting or softening of the materials that make up the prosthetic body 2.

[0202] The step of inserting at least one cartridge 100 does not take place by injection of the material that constitutes it inside the cavity or seat prepared for its housing. In fact, this insertion step only comprises placing the preformed and antibiotic-loaded cartridge 100 in the cavity or seat provided.

[0203] The step of providing of at least one cartridge 100 comprises the following steps, which must take place before the insertion step: providing a material that constitutes the cartridge 100 in the form of powder, providing at least one antibiotic, if desired, in powder form, and / or at least one pharmaceutical or medical substance and mix with the material that makes up the cartridge, hardening or polymerizing the material that makes up the cartridge 100, for example by joining a polymerizing material such as a monomer or an aqueous solution capable of solidifying and compacting the material, thus obtaining at least one cartridge 100 of the preformed type.

[0204] Eventually there may be a step of sizing or conforming the preformed cartridge, in order to adapt it to the size and conformation of the cavity or seat suitable for its housing.

[0205] As mentioned above, the surgeon can decide which cartridge 100 to use, selecting it on the basis of at least one antibiotic it contains, in order to meet the specific needs of the patient. In addition, the surgeon can also decide in which cavities or seats to insert at least one cartridge 100.

[0206] In this way, once the prosthetic device 1 is implanted in the human body, the at least one antibiotic will be released from cartridge 100, for example by contact and / or the action of biological fluids, and can escape, through the openings or holes 7, into the surrounding bone tissue, where it will perform its infection healing or preventive function.

[0207] An advantage conferred by the present invention is the fact that the at least one antibiotic is delivered substantially from the entire surface of the prosthetic device or is otherwise able to reach all bone tissue in contact with the prosthetic device according to the present invention.

[0208] In at least one version, the preferred materials are metal for the prosthetic body and PMMA-based antibiotic-loaded bone cement for the cartridge.

[0209] Other materials that can be used to make a cartridge 100 with high antibiotic release can be, in a less preferred version of the invention, TCP and all calcium salts soluble in aqueous solutions including sulfate and carbonate, water-soluble polymers such as polymers and copolymers of polylactic acid, polyglycolic acid, caprolactams, etc. The methods for creating a certain porosity in this case are substantially the same as those already indicated in the case where the cartridge 100 is made of bone cement, for example, according to a preferred version, of PMMA.

[0210] Of course, the choice of the material that makes up the 100 cartridge must be carefully evaluated on a case-by-case basis, depending on the patient's needs.

[0211] For example, water-soluble materials have the advantage of releasing ions that can be beneficial to the patient's bone tissue but, at the same time, can have the disadvantage of creating fragments of material that, in the case of a knee spacer, could migrate around the joint creating inflammation. The PMMA cartridge does not produce fragments or such risks.

[0212] According to one version of the present invention, the powdered material constituting cartridge 100 contains barium sulphate, which acts as a radiopaque agent and / or a porosizing agent. In cartridge 100, the presence of Barium Sulfate is only secondary in radiopaque function. First of all, its function is as a porosizing agent by virtue of the fact that being an inorganic salt it cannot chemically bind with MMA (Methylmethacrylate organic substance) so it remains incorporated, physically embedded in the PMMA matrix, consequently creating partially hollow crypts, therefore porous, in which biological liquids are aspirated by capillarity and thus wash away the antibiotics present in the cartridge itself. This then forms the porosity of the cartridge 100 itself.

[0213] In the same way, antibiotics, not binding in any way with MMA, create areas of porosity in the (spongy) matrix of PMMA. Among other things, as can be seen in the SEM image of figure 16, the PMMA-based bone cement matrix is spongy and / or with the appearance of a sponge.

[0214] In addition, the material that makes up the cartridge 100, regardless of porosity, can be considered a compact material, with a modest absorbency.

[0215] Example: Determination of the exchange potential surfaces of the different situations.

[0216] As is well known, bone cement exchanges very little and only by virtue of a very large surface area is it possible to obtain locally acceptable concentrations of antibiotic in order to treat or prevent an infection at the implantation site.

[0217] Taking the representation in figure 4 as an example, the external surface area of a hip prosthetic device (shown on the left) is generally equal to 12221 mm2, while the external surface of the openings is only 383 mm2. The ratio is 32, i.e. the external surface of the openings is 32 times smaller than the external surface of the prosthetic body 2.

[0218] In this case, in the left device it is the entire external surface 21 that elutes antibiotic.

[0219] The cartridge 100 (illustrated on the right) has a substantially cylindrical shape with the following measurements: diameter 4.92 mm, length 115 mm, an external surface of 1815 mm2and a volume of 2.2 ml are obtained. In this case, the surface ratio between hip prosthetic device (shown on the left) and cartridge is equal to 12221 : 1815= 6.7 times. Therefore, the external surface 101 of the cartridge 100 in this example is only about 7 times smaller than that of the prosthetic body 2.

[0220] This cartridge must be positioned, in this example, in the internal cavity 5 of the prosthetic body 2, and its external surface 21 can elute the antibiotic contained in it, which escapes towards the patient's bone tissue through the openings or holes 7 which, since the cartridge is positioned already preformed, remain accessible or empty and can therefore allow the entry of biological fluids capable of reaching the cartridge and determining the elution of the antibiotic contained in it.

[0221] Since, in fact, the dimensions of the cartridge 100 are smaller than those of the internal cavity 5 and / or the housing seat 59, it does not occlude the openings or holes 7 and the effective elution surface is the external surface 101 of the cartridge 100 and not only the surface of the openings or holes 7. Therefore, the elution surface is much larger than the latter and therefore corresponds to about 1 / 7 compared to the external surface 21 of the prosthetic device 1.

[0222] Example 2:

[0223] The amount of antibiotic that can be included in the cartridge 100 can be equal to 1g, for example about 7 times less than antibiotic-loaded spacer devices of known type and equal mass. The amount of 1g manages to escape from the prosthetic device 1 in about 1 week. In any case, it is possible to vary the speed of antibiotic delivery by acting on the porosity of the material that makes up the cartridge 100. If the porosing agent is barium sulphate, in fact, increasing its quantity will result in a high porosity and therefore a high rate of antibiotic release, while decreasing its quantity the porosity will decrease and therefore a low rate of antibiotic release.

[0224] It is therefore clear that the present invention overcomes the drawbacks of the known technique by proposing a prosthetic device equipped with an absorbent porous substrate and which clearly defines when and how the pharmaceutical and medical substance is added. In addition, the nature (solid) of the pharmaceutical or medical substance present in the device itself is specified, and in particular in its at least one cartridge.

[0225] Inthe present invention, long and careful experimental experiments have been carried out based also on decades of experience working with bone cement, in order to establish all the variables of the case, and this has led to the achievement of the present invention and its unexpected results.

[0226] Both the porous material and the solid powder form of the selected antibiotics have been chosen to give a specific and effective release profile which is illustrated, by example, in the attached images.

[0227] The prosthetic device according to the present invention therefore turns out to be a truly functional, effective and safe device for the patient. All this goes beyond the generic and theoretical teachings of prior art. The characteristics presented for one version or embodiment form may be combined with the characteristics of another version or embodiment, without leaving the scope of protection of the present invention.

Claims

CLAIMS1. Cartridge for a prosthetic device (1) capable of being implanted in a bone or joint site of the human body, wherein said cartridge has an external surface (101), wherein said cartridge (100) is made of a porous material, that is to say, with a plurality of interconnected pores, comprises at least one antibiotic and is suitable during use for releasing said at least one antibiotic to the surrounding bone tissue, wherein said antibiotic is present in a percentage between 20% and 70% by weight of the total weight of said cartridge, characterised by the fact that it is a preformed solid and by the fact that said at least one antibiotic is in the form of a powder formed by spherules and / or granules.

2. Cartridge according to claim 1, wherein said percentage of antibiotic is between 30% and 70% or between 40% and 60% or between 50% and 70% by weight of the total weight of the said cartridge and / or wherein said cartridge (100) has a substantially cylindrical, spherical, parallelepiped, prismatic or frustum of cone, frustum of pyramid shape, or in general having a three-dimensional conformation of a regular or irregular solid and / or wherein in use at least part of said external surface (101) is suitable for being in fluid communication with the bone or joint seat of the human body.

3. Cartridge according to claim 1 or 2, wherein said porous material is bone cement, e.g. PMMA-based bone cement.

4. Cartridge according to any of the preceding claims, wherein said porous material of said cartridge (100) includes an acrylic resin, a composite material comprising calcium phosphate or an inorganic salt, calcium sulphate, a bioglass, a polyvinyl alcohol, a composite material made of an acrylic resin and an inorganic salt, such as PMMA (polymethyl methacrylate) and calcium phosphate or tri-calcium phosphate (TCP), or a mixture of the same.

5. Cartridge according to any of the preceding claims, wherein said spherules and / or granules have sizes between 100 microns and 500 microns or until 0.5 mm or until 5 mm.

6. Cartridge according to claim 1 or 2, wherein said cartridge (100) is made of a water- soluble material consisting of calcium salts, such as TCP, calcium sulphate, hydroxyapatite, calcium carbonate and mixtures thereof, in such a way that said cartridge(100) is able to absorb an antibiotic aqueous solution and / or to allow its elution through contact in use with the patient's biological fluids.

7. Prosthetic device (1) suitable for being implanted in a bone or joint site of the human body, comprising a prosthetic body (2) equipped with at least one internal cavity (5, 51, 52), in particular at least one internal cavity (5) arranged along a longitudinal axis (Y) and / or at least one transverse internal cavity (51), arranged along an axis perpendicular or transverse to said axis (Y), and / or a housing seat (59), at least one cartridge (100) according to one or more of the preceding claims, characterised by the fact that said at least one cartridge is inserted into said at least one internal cavity (5, 51) and / or said housing seat (59) and by the fact that said at least one internal cavity (5, 51, 52) has slightly larger dimensions than those of said cartridge (100) and therefore comprises an empty gap (70) within said at least one internal cavity (5, 51, 52) which allows the transit of biological fluids, which are able to reach the entire external surface(101) of said cartridge (100) and to determine the elution of that antibiotic contained therein.

8. Prosthetic device (1) suitable for being implanted in a bone or joint site of the human body, comprising a prosthetic body (2) equipped with at least one internal cavity (5, 51, 52), in particular at least one internal cavity (5) arranged along a longitudinal axis (Y) and / or at least one transverse internal cavity (51), arranged along an axis perpendicular or transverse to said axis (Y), and / or a housing seat (59), at least one cartridge (100) according to one or more of the preceding claims 1 to 6, characterised by the fact that said at least one cartridge is inserted into said at least one internal cavity (5, 51) and / or said housing seat (59) and by the fact that said prosthetic body (2) comprises a series of grooves (90), said grooves (90) being recessed with respect to an external surface (21, 41, 57, 61) of said prosthetic body (2), for example longitudinal grooves (90) arranged along said longitudinal axis (Y), or grooves (90) arranged along a direction parallel to the transverse plane of the human body, with a course along an anterior-rear direction or side-side direction, or grooves (90) with radial arrangement.

9. Prosthetic device (1) according to claim 7 or 8, wherein said internal cavity (5, 51, 52) and / or said housing seat (59) has a shape corresponding to that of said cartridge (100) which it is intended to house.

10. Prosthetic device (1) according to any one of claims 7 to 9, wherein said prosthetic body (2) comprises a series of openings or holes (7) which fluidly connect said at least one internal cavity (5, 51, 52) with the bone tissue surrounding in use said prosthetic body (2), wherein said openings or holes (7) have a straight course and / or a diameter or greater dimension of 0, 5 mm to 6 mm or 0.5 mm to 4 mm or 1 mm to 3 mm or 1.5 mm to 3 mm or 0.5 mm to 10 mm or up to 12 mm or 15 mm or up to 20 mm or approximately 6 mm to 12 mm or 4 mm to 12 mm or 0.5 mm to 10 mm for side or smaller size and from 3 mm to 15 mm or from 3 mm to 20 mm or from 6 mm to 20 mm or greater, for the largest side or size and / or are evenly distributed along the entire of said wall of said prosthetic body (2) and / or wherein said openings or holes (7) are arranged along said grooves (90).

11. Prosthetic device (1) according to any of claims 7 to 10, wherein said prosthetic body (2) includes at least one tubular wall, shaped as a stem component (2a, 2b), extending along said longitudinal axis (Y), defining an external surface (21), suitable in use to be faced towards or to come into contact with a patient's bone, and an internal surface (22), wherein said internal surface (22) delimits said at least one internal cavity (5), and equipped with a first proximal end (23), as well as a second distal end (24), the latter suitable for being deeply inserted in use in the medullary canal of a patient's bone.

12. Prosthetic device (1) according to any of claims 7 to 11, wherein said prosthetic body (2) comprises a tibial plateau (40) with at least one wall, said wall having an external surface (41), suitable during use for contacting the tibial bone of the knee joint, and an articulation surface (42), suitable during use for contacting and articulating with the femoral bone of the knee joint (42) or with a femoral prosthetic component, wherein said tibial plateau (40) comprises said at least one transverse internal cavity (51), wherein said transverse internal cavity (51) is arranged in an antero-frontal direction, and / or in a side- to-side direction or may have a substantially radial course, with respect to the position in use of said tibial plateau (40).

13. Prosthetic device (1) according to any of claims 7 to 12, wherein said prosthetic body (2) comprises a femoral component (60) of a knee prosthesis equipped with at least one wall, said wall having an external surface (61), which is suitable during use for coming into contact with the femoral bone of the knee joint, as well as an articulation surface (62), suitable during use for coming into contact and articulating with the tibial bone of the knee joint or with a tibial prosthetic component or tibial plateau (40), wherein said femoral component (60) comprises said at least one transverse internal cavity (51), wherein said transverse internal cavity (51) is arranged in an antero-frontal direction, and / or in a side-to-side direction or may have a substantially radial course, with respect to the position in use of said femoral component (60).

14. Prosthetic device (1) according to any of claims 7 to 12, wherein said prosthetic body (2) includes an acetabulum or acetabular cup component (50), suitable of being inserted and / or fixed in the acetabular or cotilar cavity of a hip joint, having at least one wall defining an external surface (57), suitable during use for contacting the acetabular bone, and an articulation surface (58), suitable during use for articulation with a femoral head or with a head component of a hip prosthesis, wherein said acetabulum or acetabular cup (50) comprises at least one internal cavity (52), substantially spherical or arched or elongated in shape, and / or at least one transverse internal cavity (51), and a plurality of openings or holes (7) arranged at least at said external surface (57).

15. Prosthetic device (1) according to any of claims 13 or 14, wherein said tibial plateau (40) and / or said femoral component (60) and / or said acetabulum or acetabular cup (50) is made of a first portion or half-shell (40a, 60a) and a second portion or half-shell (40b, 60b), at least one of which may be hollow, wherein said portions or half-shells (40a, 40b, 60a, 60b) are joined by means of their respective peripheral edges (44), made in their lateral wall and facing each other, so as to constitute, once joined, the entire tibial plateau (40) and / or the entire femoral component (60) and / or the entire acetabulum or acetabular cup (50).

16. Prosthetic device (1) according to any of the claims when dependent on claim 10, wherein said openings or holes (7) are through from said external surface (21, 41, 57, 61) to said internal or articulation surface (22, 42, 58, 62) of said prosthetic body (2) or fromsaid at least one internal cavity (5, 51, 52) to said external surface (21, 41, 57, 61) of said prosthetic body (2).

17. Prosthetic device according to any of claims 7 to 16, comprising at least one insertion opening (10) for access to said internal cavity (5, 51, 52) and / or said housing seat (59), and insertion of said at least one cartridge (100).

18. Prosthetic device (1) according to any of claims 7 to 17, comprising at least one closing and / or centring means (30), for example configured as a conical or prismatic tip, suitable for closing said internal cavity (5, 51, 52) or its insertion opening (10), for example placed at said second end (24) of said stem component (2a, 2b).

19. Kit for the realization of a prosthetic device (1) comprising a prosthetic device (1) according to one or more of claims 7 to 18, and at least one cartridge (100) according to one or more of claims 1 to 6.

20. Method for the realization of a prosthetic device (1) according to one or more of claims 7 to 18, including the following steps:Providing a prosthetic body (2) delimiting at least one internal cavity (5, 51, 52) and / or at least one housing seat (59), and comprising openings or holes (7) suitable for fluidly connecting said at least one internal cavity (5, 51, 52) with the space outside said prosthetic body (2) or with the bone tissue surrounding, in use, said prosthetic body (2), providing at least one antibiotic-loaded cartridge (100) according to one or more of claims 1 to 6, inserting and placing said at least one cartridge (100) in said at least one internal cavity (5, 51, 52) and / or in said at least one housing seat (59), closing the insertion opening (10) of said at least one internal cavity (5, 51, 52) and / or of said at least one housing seat (59) by means of closing and / or centring means (30).

21. Method according to the previous claim, wherein said step of providing said at least one cartridge (100) comprises the following steps, which take place before said step of inserting and placing: providing a material constituting said cartridge (100) in the form of powder, providing at least one antibiotic and mixing it with the material that makes up said cartridge (100),hardening or polymerising the material that makes up said cartridge (100), for example by joining a polymerizing material such as a monomer or an aqueous solution capable of solidifying and compacting said material, thus obtaining said at least one cartridge (100) of preformed type.

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