• 专利附录
  • 专利说明
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    • 专利摘要:
    The invention relates to the field of bioresorbable or non-bioabsorbable bone substitutes intended for implantation in humans, intended to reconstitute the bone stock by filling a loss of substance and aims at a simple device of manufacture and use comprising a syringe equipped with a single-use dose of a fluid polymer at injection temperature and solid and resistant to body temperature.
    公开号:FR3053239A1
    申请号:FR1656231
    申请日:2016-06-30
    公开日:2018-01-05
    发明作者:Julien IEHL；Gautier HALBIN；Cyril Sender；Nouredine SAHRAOUI
    申请人:Teknimed SAS；
    IPC主号:
    专利说明:

    ® FRENCH REPUBLIC
    NATIONAL INSTITUTE OF INDUSTRIAL PROPERTY © Publication number: 3,053,239 (to be used only for reproduction orders)
    ©) National registration number: 16 56231
    COURBEVOIE © Int Cl 8 : A 61 B 17/88 (2017.01), A 61 L 24/00
    A1 PATENT APPLICATION
    ©) Date of filing: 30.06.16. (© Applicant (s): TEKNIMED Simplified joint-stock company (30) Priority: trusted - FR. @ Inventor (s): IEHL JULIEN, HALBIN GAUTIER, SENDER CYRIL and SAHRAOUI NOUREDINE. (43) Date of public availability of the request: 05.01.18 Bulletin 18/01. ©) List of documents cited in the report preliminary research: Refer to end of present booklet (© References to other national documents (® Holder (s): TEKNIMED Société par actions simpli- related: trusted. ©) Extension request (s): (© Agent (s): REGIMBEAU.
    (□ 4) BONE SUBSTITUTE AND AUTONOMOUS INJECTION SYSTEM.
    13 /) The invention relates to the field of bone substitutes, bioresorbable or not, intended for implantation in humans aiming to reconstitute the bone stock by filling a loss of substance and is aimed at a simple device for manufacturing and use comprising a syringe with a single-use dose of a fluid polymer at injection temperature and solid and resistant to body temperature.
    FR 3 053 239 - A1
    BONE SUBSTITUTE AND AUTONOMOUS INJECTION SYSTEM
    The present invention relates to the field of bioresorbable bone substitutes or not, intended for implantation in humans aiming to reconstitute the bone stock by filling a loss of substance.
    The invention relates more particularly to the field of bone filling under mechanical stress.
    Osteoporosis is an important medical problem, and increasingly an important economic problem. More than a third of women and about one in seven men aged 50 will experience a fracture secondary to their osteoporosis once in their lifetime.
    The fracture of the vertebral body is the most frequent. The first transcutaneous vertebroplasty was performed in 1984. Galibert et al. treated a cervical vertebral angioma by transcutaneous puncture and filling of the vertebral body with polymethylmethacrylate cement (PMMA). For several years, vertebroplasty has been more and more accepted in the treatment of osteoporotic vertebral fractures.
    Vertebroplasty consists in injecting a cement, for example acrylic, percutaneously into the vertebral bodies under fluoroscopic and / or tomographic control. The vertebroplasty method has been perfected, with the aim of restoring the generally wedge-shaped vertebral body to its original form. Kyphoplasty involves dilating (ie reducing) the vertebral body using an inflatable balloon before injecting cement.
    These techniques help reduce pain, limit painkillers and shorten hospitalization. Within 72 hours after a vertebroplasty, 85 to 90% of patients with osteoporotic vertebral fractures benefit from a remarkable, or even total, reduction in their pain.
    Acrylic resins have a high mechanical resistance of the order of 80 to 90 MPa in compressive strength, and are used in these bone filling techniques under stress. PMMA cement has several drawbacks. It is recognized that the in vivo hardening of PMMA cements generates free radicals. Furthermore, the polymerization reaction of these materials is exothermic and the heat given off during curing is high, which can exceed 90 ° C, and can damage the surrounding tissues. Absorbable and biocompatible bone substitutes such as phosphocalcic ceramics, bio-glasses and other implantable medical devices available in the form of blocks or granules have insufficient mechanical strength. Phosphocalcic cements, despite their hardening in situ and a mechanical resistance of 4 to 20 MPa for the most resistant, do not meet the specifications of bone filling techniques under stress either.
    Bone substitutes have thus been developed associating an agent of the phosphocalcic ceramic type or of the bone type with one or more bioresorbable polymers.
    For example, EP2395949 describes a bone substitute material which is fluid or pasty when it is heated to a temperature of 70 to 95 ° C. and thus extrudable and injectable at an implantation site. Once cooled, the material solidifies and reabsorbs, leaving room for bone tissue. It is further indicated that the invention described by EP2395949 is based on the principle of heating a bone substitute which becomes fluid at an elevated temperature via a device used to administer said heated material.
    Many combinations are described such as bone / polymer, mineral / polymer, ceramic / polymer composites. The polymer can be a polycaprolactone, a poly (lactide-coglycolide) or even a polyurethane. Examples of composite bone substitute materials are described with reference to documents US2005 / 0008672, WOO4 / 53112, WO2007 / 084725, US2008 / 0069852 and US2007 / 0191963. These documents describe osteoimplants comprising a combination of polymers of various origin and chemical nature associated with a bone derivative, an inorganic material, a bone substitute material or a combination thereof.
    WO2003 / 059409 describes an implant comprising anhydrous calcium sulphate added with a bioabsorbable polymer and calcium phosphate. The bioabsorbable polymer can be a polymer or copolymer of lactic acid, glycolic acid, hydroxybutyric acid, hydroxyvaleric acid, polydioxane, polycaprolactone, polyethylene oxide or polyethylene terephtatate. However, this document does not disclose an implant being able to be used by heating to a temperature of the order of 60 ° allowing its fusion and its administration in a particular bone point.
    US2008 / 0003255 describes thermoplastic materials for bone repair. Aliphatic polyesters and in particular polycaprolactone are described therein as suitable material. It is indicated that polycaprolactone with a molecular weight greater than 100,000 has a melting temperature around 60 ° C which allows it to be injected. It is also stated that this material can be heated and injected using a heat gun.
    US 8562619 describes a method, a material and a device for injecting said material for bone filling and / or repair. The method explained consists of heating a composition of bone cement in order to make this composition fluid, of injecting it into the area to be filled so that it solidifies there. It is indicated that the injection temperature is lower than that of the initial melt in order to avoid necrosis but nevertheless makes it possible to maintain fluidity. It is indicated that the composition of bone cement comprises a biocompatible thermoplastic polymer whose melting temperature is between 70 and 200 ° C. in addition to calcium phosphate. The biocompatible thermoplastic polymer described can be chosen from: poly (lactic-co-glycolic acid, polylactic acid, poly glycolic acid, polyhydroxybutyrate, polyalkylene succinate, polybutylene diglycolate, polycaprolactone and combinations thereof. The only examples disclosed relate to poly-lactic-glycolic acid and the melting temperatures of the mixtures tested are in a range greater than 100 ° C. The compositions described in this document require the use of very high temperatures in order to ensure their fluidity.
    In particular, it should be noted that all the documents cited above require the use of heating and delivery devices for the complex and expensive composition.
    Typically, these are pistol-type devices provided with a reservoir and a cannula associated with an integrated heating and thermoregulation system which delivers sufficient heat to make the bone substitute material fluid.
    In such devices the amount of heat is regulated either directly by the user or via an electronic feedback system to keep the material flowing. Such delivery devices generally include a handle, a housing and a chamber for the material to be delivered. These devices resemble a gun provided with a reservoir intended to receive the bone substitute type material as described above, with a cannula and with means of heating and thermostating (integrated or remote) of the material at the reservoir and beginning of the cannula in order to maintain the material in fluid form before its injection into an implantation area.
    These devices are complex both in their manufacture, their use and their maintenance. They are also expensive and heavy to handle by a surgeon. In addition, to ensure thermostat control, a wired electrical connection or a battery is necessary, which further complicates use and / or creates an electrical risk for the patient. Finally, their use involves steps of manipulation of bone substitute type material in order to "load" the heating and extrusion chamber of the device. In addition, after each use, the pistol-type device must be cleaned and sterilized and a large part of said device containing the material residue must be dismantled and separated to be discarded. At each use, the sterile gun type device must be reassembled with the disposable part, which is also sterile, loaded with a dose of sterile filling material, heated and thermostated. All these manipulations must be carried out while maintaining sterility and asepsis, which for heavy and complex equipment is either very complicated or very expensive.
    There is therefore a need for new systems of materials in new delivery formats associated with new devices for their manipulation and injection in the context of bone filling techniques under high mechanical stress making it possible to solve the aforementioned problems by providing simplicity, comfort, convenience of use for the surgeon while ensuring safety for the patient.
    It is thus a first object of the present invention to provide a composition for bone filling packaged in the form of a single-use dose, such as a stick, comprising, or consisting of, at least one polymeric material.
    absorbable or not absorbable characterized in this than said composition presents a viscosity included ; Between 40 and 4000 Not in particular between 50 and 3000 Not, , more particularly still between 80 and 2500 Not , more particularly still between 150 and 2000 Pa.s, between 200 and
    1500 Pa. S and at a temperature of around 50 ° C and a Young's modulus between 0.5 and 4 GPa, particularly between 1 and 4
    GPa, between 1 . 5 and 3.5 GPa, more particularly still between 2 and 3 GPa, and this at 37 ° C approximately. The expression dose for single use gets along in the background of the
    present invention in that the amount of composition is suitable for surgical intervention on a patient for at least one bone filling or any type of intervention involving additional material in a place where the bone is lacking. This single-use dose also means that it is continuous and in a single-use form and suitable for use in a device according to the invention as described below.
    The polymer material can be absorbable or non-absorbable depending on the indications envisaged.
    The polymer material is chosen such that the composition thus has a viscosity of between 40 and 4000 Pa.s, more particularly 50 and 3000 Pa.s, more particularly still between 80 and 2500 Pa.s, more particularly still between 150 and 2000 Pa .s, between 200 and 1500 Pa.s and this at a temperature of around 50 ° C.
    This characteristic reflects the fact that the composition is fluid at this temperature and can thus be easily extruded through a cannula and injected into a bone point in a patient and this without risk of burning or necrosis of the tissues of this patient.
    In addition, the polymer material of the composition is such that said composition has, after cooling, and more particularly at a temperature of approximately 37 ° C., a hardness such that the Young's modulus of said composition is between 0.5 and 4 GPa, particularly between 1 and 4 GPa, between 1.5 and 3.5 GPa, more particularly still between 2 and 3 GPa, and this at approximately 37 ° C.
    The expression “fluid” thus means a composition which is made runny or whose viscosity is between the values indicated above, that is to say between 40 and 4000 Pa.s, a temperature of approximately 50 ° C.
    The composition made "fluid" by heating can thus pass through a cannula with a diameter between
    Heating the la and 15 gauges composition above the melting temperature or glass transition temperature of the polymer allows the fluidization of said composition as well as its progression through the cavity of a cannula by application of pressure in order to ensure its progress.
    The Young's modulus of the composition after cooling, in particular at 37 ° C., is such that it is advantageously between 2 and 3 GPa.
    Such hardness makes it possible to ensure a high mechanical resistance of the composition after its implantation in a bone cavity and thus to constitute a durable or absorbable osteoimplant depending on the nature and the quality of the components of the composition.
    By “osteoimplant” is meant here any material used to help or increase defective bone formation. Osteoimplants are often applied to fill and complement a bone defect resulting from an injury, a malformation, a deformation, a defect or even surgery for example. An osteoimplant can be used in a variety of surgeries, from orthopedic surgery to neurosurgery, for example.
    The polymer of the composition according to the invention may be an absorbable polymer and be chosen from the group consisting of poly (lactic-co-glycolic acid), polylactic acid, polyglycolic acid, poly (caprolactone), polyhydroxybutyrate, polyglycerolsebacate, poly (dioxanone) used alone or as a mixture.
    The polymer of the composition according to the invention may be a non-absorbable polymer and be chosen from the group consisting of polymers and copolymers of acrylates and methacrylate, polyetheretherketone, polyurethane, polyethylene, polypropylene, polyethylene terephthalate, used alone or as a mixture.
    In a particular embodiment, the polymer is an absorbable polymer and it is polycaprolactone.
    In a particular embodiment, the polymer is a polycaprolactone with a molecular weight of between 10,000 and 100,000, particularly between 30,000 and 60,000, more particularly between 30,000 and 50,000, more particularly around 40,000.
    The molecular weight of polycaprolactone determines the temperature of this polymer and therefore of the composition. The lower the molecular weight, the lower the melting temperature. However, this molecular weight also determines the hardness of the material at a temperature of the order of 37 ° C, that is to say the body temperature. Thus a low molecular weight leads to a friability of the hardened material, which is not acceptable. On the other hand, the viscosity of the heated material above its melting temperature is largely determined by its molecular weight. Also the viscosity is proportional to the molecular weight.
    It is therefore advisable to choose a polymer whose viscosity in the molten state allows on the one hand an extrusion and an easy injection of the composition and this without excessive effort while having a temperature compatible with the biological tissues of the patient.
    Finally, the mechanical strength of the composition once in and cooled to body temperature must be high enough to play its role as filling material and withstand mechanical stresses.
    Thus the polymer can be chosen by a person skilled in the art by routine tests consisting in measuring the melting temperature or the glass transition temperature and the associated viscosity and in retaining the polymers making it possible to obtain a composition of which the viscosity is as indicated above, at the temperature of approximately 50 ° C.
    A second grid for selecting the suitable polymer consists in measuring the Young's modulus of the composition comprising, or consisting of, the polymer and in retaining that which makes it possible to obtain a Young's modulus of the composition between 0.5 and 4 GPa , particularly between 1 and 4 GPa, between 1.5 and 3.5 GPa, more particularly still between 2 and 3 GPa, and this at around 37 ° C.
    In another embodiment, the composition in the form of a single-use dose, such as a stick, according to the invention further comprises an inorganic material, more particularly an inorganic biomaterial, more particularly still a phosphocalcic biomaterial.
    Also, the polymer / inorganic material mass ratio of the composition according to the invention can be between 100/0 and 40/60 for example, more particularly between 90/10 and 50/50, more particularly still between 80/20 and 70 /30.
    This ratio also influences the viscosity of the composition at the time of injection as well as the resistance of the solidified composition, that is to say the osteoimplant, once placed in the cavity which is filled. The ratio will be determined in conjunction with the nature of the polymer and the viscosity of said polymer and its hardness so that the viscosity of the composition at 50 ° C. is between 40 Pa.s and 4000 Pa.s and that the modulus of Young of the composition at approximately 37 ° C. is between 0.5 and 4 GPa, particularly between 1 and 4 GPa, between 1.5 and 3.5 GPa, more particularly still between 2 and 3 GPa.
    The single-use dose of the composition according to the invention is sized to correspond to one or more bone fillings and is between 2 and 50 ml, preferably between 4 and 12 ml.
    Advantageously, the single-use dose is in the form of a rod of cylindrical section, the dimensions of which can be of the order of 4 to 10 cm in length and 1 to 3 cm in diameter. Such a format allows the use of such a dose in a device as explained later in the description.
    According to one embodiment, the phosphocalcic phosphocalcic biomaterial, particularly strontic calcium.
    type inorganic material is a bioceramic a phospho bioceramic. The phosphocalcic phosphocalcic material has the advantage that a bioceramic is of being bioresorbable.
    Preferably, said bioceramic comprises or consists of one or more sintered phosphocalcic compounds chosen from the group consisting of hydroxyapatite (HA), alpha- and betatricalcium phosphate (o-TCP, β-TCP) and two-phase phosphocalcic material (BCP) or one of their mixtures.
    In a particularly preferred manner, said bioceramic comprises a two-phase phosphocalcic material, comprising or consisting of approximately 80% HA and approximately 20% TCP or approximately 20% HA and approximately 80% β-TCP.
    In one embodiment, the basic inorganic material is an absorbable phosphocalcic biomaterial. In particular, the phosphocalcic biomaterial is complemented by a substitution of one or more calcium atoms by strontium atoms. The addition of a strontium atom increases the radio-opacity of the final biomaterial proportionally.
    The inorganic compound of the phosphocalcic biomaterial type can be chosen from the group comprising amorphous calcium phosphate (ACP), Ca x (PO 4 ) y. H 2 O; monocalcium phosphate monohydrate (MCPH), CaH 4 (PO 4 ) 2 · H 2 O; dicalcium phosphate dihydrate (DCPD), CaHPO 4 .2H 2 O; anhydrous dicalcium phosphate (DCPA), CaHPO 4 ; precipitated or calcium deficient apatite (CDA), (Ca, Na) 10 (PO 4 , HPO 4 ) 6 (OH) 2 ; alpha- or beta-tricalcium phosphate (o-TCP, β-TCP), Ca 3 (PO 4 ) 2 ; and tetracalcium phosphate (TTCP), Ca 4 P 2 O 9 .
    More specifically, the composition according to the invention in the form of a single-use dose is in the form of a stick and comprises by weight 40 to 100% of a polycaprolactone polymer of molecular weight between 10,000 and 100,000, more particularly between 30,000 and 60000, 0 to 60% of a phosphocalcic biomaterial, in particular a phosphocalcic biomaterial comprising hydroxyapatite and / or tricalcium phosphate.
    Advantageously, the polycaprolactone polymer is absorbable.
    Advantageously, the hydroxyapatite / tricalcium phosphate weight ratio in the phosphocalcic biomaterial is between 80/20 and 20/80, more advantageously still between 65/35 and 35/65.
    According to a particularly advantageous embodiment of the invention, the phosphocalcic biomaterial according to the invention comprises by weight 65% of hydroxyapatite and 35% of strontic tricalcium phosphate.
    The inorganic material of the composition according to the invention can also be chosen from the group consisting of bioverres, silicates, in particular aluminosilicates, calcium sulfates, barium sulfates.
    The composition according to the invention can comprise organic compounds and molecules such as polysaccharides, proteins or peptides, lipids for example.
    The compositions according to the invention are of great utility for new surgical techniques which are increasingly practiced, such as vertebroplasty or kyphoplasty or osteoplasty more generally, for example.
    These operations require materials of a radio opaque nature (permanently or not depending on the case). They are in fact performed on more or less fractured vertebrae and the leakage of material outside the vertebrae can be critical, giving rise to neurological and vascular complications which can lead to death. It is therefore essential that the surgeon can observe the quantity of product injected, its dispersion in the vertebra and above all check that the material remains inside it.
    According to the invention, radio opaque agents for medical X-ray imaging can be added to the compositions according to the invention. They may be iodine, ionic or nonionic compounds such as Iomeron® or Iopamidol®. These iodized solutions make the gel completely radio-opaque and therefore make it possible to detect it by X-ray radiography. The stronsic derivatives can also be envisaged as mentioned above.
    In the case of absorbable products, the radio opaque agents and compounds present in the composition, once injected, have the additional advantage of disappearing over time, which makes it possible to assess the effectiveness of bone reconstruction.
    In addition, the compositions according to the invention exhibit, after heating, exceptional rheological properties.
    They form viscous products, of thick structure in the form of paste injectable through a cannula at a temperature
    around 50 ° C in Release said cannula. The invention at also for object use of compositions according to 1 ' invention as that bone substitute for
    vertebroplasty.
    The invention also relates to the process for the preparation of the compositions described above. Such a method comprises the following successive steps:
    preparation of a homogeneous mixture comprising the polymer, particularly an absorbable polymer of the polycaprolactone type with a molecular weight of between 10,000 and 100,000 and optionally an inorganic material;
    The mixing is carried out according to a controlled mechanical or chemical process;
    The mixture makes it possible to obtain forms such as a stick after passing through an injection molding machine.
    Sterilization of the product obtained can be carried out by means known to those skilled in the art, for example with ethylene oxide.
    Another object of the present invention also resides in a syringe-type device containing the composition according to the invention for the injection into a bone point of said composition in order to produce bone filling.
    In particular, the invention therefore relates to an assembly consisting of a syringe and a single-use dose of a composition according to the invention, said syringe being pre-filled with said unitary composition according to the invention, said syringe allowing both storing and administering said composition, said syringe further comprising a syringe body comprising at each of its two ends an opening, the first opening carrying sealing means for sealing, in particular a stopper, and / or means for administering said composition, in particular a cannula, the second opening being closed in leaktight manner by closing means, in particular a piston seal, capable of sliding inside the syringe body, in particular on the using a piston rod, in particular linked to said closure means capable of sliding, said syringe body, said closure and / or administration means, and said closure means capable of sliding defining a volume in which said composition is included.
    An object of the present invention is therefore a device comprising:
    a syringe pre-filled with a single-use dose of a composition for bone filling, such as a stick, said composition comprising at least one absorbable or non-absorbable polymeric material, said composition having a viscosity of between 40 and 4000 Pa.s at a temperature of approximately 50 ° C. and a Young's modulus of between 0.5 and 4 GPa at approximately 37 ° C., said syringe making it possible both to store and administer said composition, said syringe comprising a syringe body comprising each an opening at its two ends, the first distal opening carrying sealing means for sealing, in particular a plug, and / or means for administering said composition, in particular a cannula, the second proximal opening being closed for sealing by closure means, in particular a piston seal, capable of sliding inside the syringe body, in particular using a piston rod designed to be moved in the direction of the distal opening, in particular linked to said closure means capable of sliding, said syringe body, said closure and / or administration means, and said closure means capable of sliding defining a volume in which said dose is included;
    - A means of external heating and structurally separate from the syringe and allowing its heating and a fusion of the dose of the composition for bone filling for the purposes of its administration.
    The body of the syringe according to the invention may be made of any material resistant to heating at a temperature between 80 and 120 ° C; and in particular the body of the syringe is made of metal. The particularly suitable metal is aluminum, given its lightness and its thermal inertia allowing good thermal conductivity.
    The piston rod can be a threaded rod making it possible to advance the composition after heating and fluidization by screwing said piston rod. In this case, the end through which the piston rod passes may be provided with a thread complementary to the thread of the piston rod.
    The use of pre-filled syringes according to the invention avoids practitioners the steps of transferring the filling product from its container to an administration device as mentioned above, which, beyond improving the comfort of use, guarantees better sterility of the product.
    Indeed, the use of pre-filled syringe allows a single use which on the one hand facilitates the handling and limits all the risks of bad dosage.
    According to an advantageous embodiment, the present invention relates to an assembly according to the invention as described above, in which the volume of the dose of the single-use composition stored in the syringe is from 1 to 50 ml, preferably from 2 to 35 ml, more preferably from 4 to 20 ml.
    The expression single-use dose is understood in the context of the present invention in that the quantity of composition is suitable for surgical intervention on a patient for at least one bone filling or any type of intervention involving additional material. in a place where bone is missing. This single-use dose also means that it is continuous and in a single-use form and suitable for use in a device according to the invention. This dose may be in the form of a stick of absorbable polymeric material occupying the internal volume of the syringe, but it may also be beads or granules of said material.
    The volume of said dose of single-use composition is less than or equal to the maximum volume that said syringe can contain. According to a particularly advantageous embodiment, the present invention relates to an assembly as described in which the volume of the dose of said single-use composition stored in said syringe is from 1 to 20 ml, preferably from 2 to 10 ml , more preferably from 4 to 10 ml. According to another particularly advantageous embodiment, the present invention relates to a device in which the volume of the dose of said disposable composition, stored in said syringe is from 10 to 50 ml, preferably from 10 to 35 ml, more preferably from 10 to 20 ml.
    According to a particularly advantageous embodiment, the present invention relates to an assembly in which the means or means for administering the composition is or are abutted at the end of the body of the syringe and comprise or consist of a cannula whose diameter is between 8 and 15 gauges, in particular from 10 to 14 gauges.
    The volume of the syringe can be modified by sliding said closure means inside the body, in the direction of the first distal opening, said opening being in particular free from closure means. When the first distal opening carries closure means, in particular a plug and administration means, in particular a cannula, said closure means, initially sealed, are subsequently pierced during placement said means of administration. In this case, it is not necessary to replace said closure means with said administration means to administer said composition. A piston rod can be adapted to said piston seal, to allow the administration of said composition, said administration being manual, or carried out by means of automated administration.
    In a particular embodiment, the pre-filled syringe according to the invention, with or without means of administration, is heated to a temperature higher than the melting temperature of the composition for bone filling contained in the body of the syringe.
    This heating can be achieved by any suitable means known to those skilled in the art but which is external and structurally separated from the syringe. This characteristic of the device according to the invention indeed makes it possible to have a means of storage and administration of the Composition, ie the syringe, devoid of integrated electrical or electronic heating systems as exists in the prior art. This configuration provides a simple, economical and robust system to manufacture and use. In particular, prior to its use, the prefilled syringe, whether or not equipped with administration means, may be placed in an oven thermostatically controlled at a temperature between 80 ° C and 120 ° C, particularly between 80 ° C and 90 ° vs. The syringe could just as easily be heated using a sheath or heating collar of the type sized to receive the body of the syringe whether or not equipped with an injection cannula.
    The syringe is therefore used as a storage medium or coolant tank.
    In a particular embodiment, the external and structurally separate heating means of the syringe can be a suitable oven for thermostating the syringe containing the composition according to the invention and is in the form of a cylinder whose diameter is substantially equal while by being slightly higher than that of the syringe in order to be able to introduce it into the body of said oven. Likewise, the length of this cylinder will be substantially equal to or slightly greater than the overall length of the assembly according to the invention. The assembly may or may not include a cannula butted at one end, the length of the cylinder of the oven may be such that it is at least equal to the length of the syringe including the cannula, if present, in order to ensure the heating of this cannula.
    It is also an object of the present invention to provide a device according to the invention in which the heating means comprises an oven in the form of a heating cylinder whose diameter is substantially equal while being slightly greater than that of the syringe in order to be able to introduce it into the body of said oven and the length of which is substantially equal to or slightly greater than the overall length of the device.
    The heating cylinder of the oven can be equipped with electric heating resistors ensuring the rise in temperature or any other means allowing this rise in temperature, for example induction.
    Indeed, the melting temperature of the composition for bone filling according to the invention is established between 50 ° C and 60 ° C and this according to the nature of the polymer, the molecular weight of the polymer, more particularly of the absorbable polymer of polycaprolactone thus as the amount of this polymer in said composition. As mentioned above, the higher the molecular weight, the higher the melting temperature. In addition, the presence of an inorganic compound of the phosphocalcic biomaterial type in the composition will tend to lower the melting temperature of the composition.
    Thus, the thermostat temperature of the assembly according to the invention, that is to say of the syringe containing the dose of single-use composition for bone filling, will be determined by the volume and the nature of said composition.
    As mentioned above, a thermostat temperature of the assembly according to the invention of the order of 90 ° C for a time of the order of 3 to 20 minutes, for example, making it possible to reach a temperature of 80 ° C. approximately at the heart of the single-use dose of the composition thus allows a fluidification of said composition contained in the syringe body compatible with an injection, in particular in the vertebral body of the patient through suitable tubing. This core temperature can of course be adapted according to the nature of the composition used.
    In fact, as indicated above, the first end of the body of the syringe is equipped with means for dispensing the composition, in particular a surgical cannula.
    The length of this cannula can be chosen according to the desired application and will be of the order of 100 to 150 mm.
    Typically, during the extrusion of the fluidized composition via the application of a force at the level of the plunger rod, the progression of the fluid composition along the cannula implanted in the patient's body causes the latter to cool. this. Similarly, once the composition arrives in the cavity to be filled, a drop in temperature is also observed.
    It is therefore necessary to provide an adequate temperature of the composition within the body of the syringe so that after progression along a cannula placed in a bone cavity of the patient, via a trocar, and at the outlet of said cavity, the composition has not solidified. Thus, a temperature of the preferred composition according to the present invention, in the body of the syringe of the order of 80 ° C., makes it possible to obtain a fluid and injectable composition which retains its fluidity once it has reached the end d '' a 150 mm cannula with a temperature of 45 to 50 ° C.
    At the outlet in the bone cavity, in contact with the internal environment of the patient, the temperature of the composition is established at around 40 to 45 ° C. which allows said composition, which is still more or less fluid, to fill effectively
    the empty • A Phone profile of temperature allows to reconcile a deliverance and a inj ection efficient and to preserve tissue of the patient of all risk of necrosis.
    An object of the invention also relates to a kit comprising an assembly according to the invention and a cannula for injection of the composition.
    When implementing the assembly or the kit according to the invention, the obturator at the end of the syringe is removed, a cannula, particularly that included in the kit, is fixed at said end and the the whole is heated in a suitable heating device such as a cylindrical oven as mentioned above for example.
    In the case of the use of the composition in vertebroplasty, during the heating of the assembly, the surgeon will be able to proceed to the positioning of a trocar at the level of the fractured vertebra or to be treated for example. This can be done safely under continuous radiographic control during the operation. A balloon can then be inserted through the trocar into the vertebra and then inflated. We can thus restore the vertebra, which is raised, allowing the formation of a cavity. After withdrawal of the balloon, the cannula of the syringe is introduced into the trocar and the composition is extruded and the cavity of the filling composition is filled.
    The composition is completely hard after a few minutes.
    The body of the syringe is preferably made of metal, and more particularly of aluminum, which allows rapid heat transfer towards the interior and allows liquefaction of the composition contained while guaranteeing sufficient thermal inertia to keep the composition in a state melted and at a satisfactory viscosity to be extruded.
    In addition, if the surgeon wishes, during administration, to make the composition contained in the syringe and / or cannula more fluid, it will suffice to reintroduce it into the heating means to ensure liquefaction of said composition for the purpose of its issue.
    In a particular embodiment, and in order to facilitate the manipulation of the syringe by the surgeon, an insulating sheath entirely or partially enveloping the syringe and the means for closing and / or administering the composition is arranged at the level of the body of said syringe.
    This sheath can be secured to the body of the syringe or removable.
    This sleeve, integral or removable, can slide along the longitudinal axis of the body of the syringe and completely or partially cover said body, lock and allow the body of the syringe to be held while allowing the piston rod to advance, for example by screwing or pushing. Such a sheath makes it possible to protect the surgeon or any person handling the syringe from a burn due to the temperature of the body of the syringe leaving the heating device. The sheath can also, for example, be in the form of two half shells connected by a hinge taking pincers from the syringe and ensuring its maintenance.
    In fact, when the assembly is introduced into a heating device, the insulating sheath is slid, or removed, so that it no longer covers the body of the syringe which is thus heated independently of said sheath. Once the body of the syringe is brought to the desired temperature, said sheath is slid in the opposite direction, so as to cover the body of the syringe. In the case of a removable sheath, this is repositioned on the syringe body. This sheath can be locked in one or the other or the two sliding positions, preferably in the position completely covering the body of the syringe in order to allow a gripping of said body and a thrust of the composition contained. Locking can be achieved via a bayonet system via a push-turn movement for example.
    The insulating protective sheath can be made of any material as long as it is weakly conductive of heat or even thermal insulator. It may for example be silicone resin or polycarbonate polymer or any other material with low thermal conductivity.
    The present invention overcomes the steps of extemporaneous preparation of cements or handling of materials in the form of granules which are introduced into a heating chamber of a heating gun.
    The assembly according to the invention, a pre-filled syringe, can be sterilized and packaged and can be used directly in the operating room while minimizing handling.
    In addition, after heating and during handling, if the composition contained in the body of the syringe or already present in the cannula were to solidify, it suffices to return the assembly to be heated in the external heating means, such as an oven. or heating sheath, to fluidize the composition again and resume injection.
    This advantage is not possible with existing heat gun type devices because the associated cannula is not heated and when the composition contained therein is solidified, it is necessary to remove this cannula and start heating again.
    The system according to the invention has the advantage of comprising a syringe which is structurally separated from any external means of heat or energy once it has been heated to the appropriate temperature, which makes it an autonomous heat transfer system. Thus the absence of battery, electrical resistance, electric wires ensuring the connection to an external source of electricity allows an easy manipulation for the surgeon and makes it possible to eliminate any electrical risk for the patient. Finally, the mechanically simple design of the system according to the invention allows its mass production and this for a competitive price.
    A system according to the invention therefore has the advantage of being easy to handle, easy and inexpensive to manufacture and can be discarded after use.
    EXAMPLE 1
    Measurement of rheological properties
    The material used consists of:
    MCR51 viscometer
    Climatic chamber 3-EC-02 (SLH 100 - Sécasi)
    Rheoplus software
    The tests for measuring the viscosity of the polycaprolactone polymer are carried out using an Anton Paar Model MCR51 rheometer / viscometer in dynamic shear mode (1 Hz). This device makes it possible to record the evolution of complex viscosity as a function of time and at a constant temperature. In order to approach the actual conditions of use of the heating injector, the polymer is melted at 90 ° C in the device and then a set temperature is set (temperature at which the material will arrive in the bone site to be filled). The acquisition of the measurements is started when the desired temperature (50 ° C) of the support is stable.
    EXAMPLE 2.
    Composition PCL + strocal phosphocalcic agent
    PCL with molecular mass Mn = 30 OOOg / mol + β-TCP strontium
    PCL / phosphocalcic agent ratio
    PCL / β-TCP (Sr) = 70/30
    Phosphocalcic agent particle size β- ^ Ρ (Ξη) = 30 pm
    Injection device / syringe
    Injection device according to the invention with a metal cartridge loaded with a stick of PCL / TCP material (Sr) connected to a cannula of gauge 11 which can be introduced into a trocar of gauge 10. The heating of the device before the transfer for injection into the vertebra is carried out in an oven thermostatically controlled at 90 ° C.
    权利要求:
    Claims (14)
    [1" id="c-fr-0001]
    1. Device comprising:
    a syringe pre-filled with a single-use dose of a composition for bone filling, such as a stick, said composition comprising at least one absorbable or non-absorbable polymeric material, said composition having a viscosity of between 40 and 4000 Pa. s at a temperature of approximately 50 ° C. and a Young's modulus of between 0.5 and 4 GPa at approximately 37 ° C., said syringe making it possible both to store and to administer said composition, said syringe comprising a syringe body comprising each of its two ends an opening, the first distal opening carrying sealing means for sealing, in particular a plug, and / or means for administering said composition, in particular a cannula, the second proximal opening being closed so sealed by closure means, in particular a piston seal, capable of sliding inside the syringe body, in particular using a rod e piston designed to be moved in the direction of the distal opening, in particular linked to said closure means capable of sliding, said syringe body, said closure and / or administration means, and said closure means capable of slide delimiting a volume in which said dose is included;
    - A means of external heating and structurally separate from the syringe and allowing its heating and a fusion of the dose of the composition for bone filling for the purposes of its administration.
    [2" id="c-fr-0002]
    2. Device according to claim 1, characterized in that the body of the syringe is made of metal.
    [3" id="c-fr-0003]
    3. Device according to claim 1, characterized in that the volume of the dose of the disposable composition stored in the syringe is from 1 to 50 ml.
    [4" id="c-fr-0004]
    4. Device according to claim 1, characterized in that the means for administering the composition are abutted at the end of the body of the syringe and comprise a cannula whose diameter is between 8 and 15 gauges, in particular 10 to 14 gauges.
    [5" id="c-fr-0005]
    5. Device according to claim 1, characterized in that the polymer material is an absorbable polymer and is chosen from the group consisting of poly (lactiqueco-glycolic acid), polylactic acid, polyglycolic acid, polyhydroxybutyrate, poly (caprolactone), polyglycerolsebacate, methacrylate, polyethylene, poly (dioxanone) used alone or as a mixture.
    [6" id="c-fr-0006]
    6. Device according to claim 1, characterized in that the polymer material is a non-absorbable polymer and is chosen from the group consisting of polymers and copolymers of acrylates and polyetheretherketone, polyurethane, polypropylene, polyethylene terephthalate, used alone or as a mixture .
    [7" id="c-fr-0007]
    7. Device according to claim 1, characterized in that the polymeric material is a polycaprolactone of molecular weight between 30,000 and 60,000.
    [8" id="c-fr-0008]
    8. Device according to claim 1, characterized in that the composition further comprises an inorganic material, more particularly an inorganic biomaterial, more particularly still a phosphocalcic biomaterial.
    [9" id="c-fr-0009]
    9. Device according to claim 8, characterized in that phosphocalcic biomaterial is a phosphocalcic, particularly a strontic phospho-calcium.
    [10" id="c-fr-0010]
    10. Device according to claim 9, characterized in that the bioceramic comprises or consists of one or more sintered phosphocalcic compounds chosen from bioceramic bioceramic the group consisting of hydroxyapatite (HA), alpha- and beta-tricalcium phosphate (o-TCP, β- TCP) and two-phase phosphocalcic material (BCP) used alone or as a mixture.
    [11" id="c-fr-0011]
    11. Device according to claim 1, characterized in that the polymer / inorganic material mass ratio of the composition is between 100/0 and 40/60, more particularly between 90/10 and 50/50, more particularly still between 80/20 and 70/30.
    [12" id="c-fr-0012]
    12. Device according to claim 1 characterized in that the composition is in the form of a stick and comprises by weight 40 to 100% of a polycaprolactone polymer of molecular weight between 30,000 and 60,000, 0 to 60% of a phosphocalcic biomaterial , in particular a phosphocalcic biomaterial comprising hydroxyapatite and / or tricalcium phosphate.
    [13" id="c-fr-0013]
    13. Device according to claim 1 characterized in that an insulating sheath entirely or partially enveloping the syringe and the means for closing and / or administering the composition is arranged at the level of the body of said syringe.
    [14" id="c-fr-0014]
    14. Device according to one of the preceding claims, characterized in that the heating means comprises an oven suitable for thermostating said device, said oven being in the form of a heating cylinder whose diameter is substantially equal while being slightly greater than that of the syringe in order to be able to introduce it into the body of said oven and the length of which is substantially equal to or slightly greater than the overall length of the device.
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    同族专利:
    公开号 | 公开日
    EP3478225A1|2019-05-08|
    US11141206B2|2021-10-12|
    FR3053239B1|2022-02-25|
    WO2018002335A1|2018-01-04|
    US20190216515A1|2019-07-18|
    BR112018077374A2|2019-04-09|
    JP2019521767A|2019-08-08|
    CN109803613A|2019-05-24|
    KR102343181B1|2021-12-24|
    KR20190033532A|2019-03-29|
    CN109803613B|2021-11-12|
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    法律状态:
    2017-06-15| PLFP| Fee payment|Year of fee payment: 2 |
    2018-01-05| PLSC| Publication of the preliminary search report|Effective date: 20180105 |
    2018-06-13| PLFP| Fee payment|Year of fee payment: 3 |
    2019-04-26| PLFP| Fee payment|Year of fee payment: 4 |
    2020-04-24| PLFP| Fee payment|Year of fee payment: 5 |
    2021-04-22| PLFP| Fee payment|Year of fee payment: 6 |
    优先权:
    申请号 | 申请日 | 专利标题
    FR1656231|2016-06-30|
    FR1656231A|FR3053239B1|2016-06-30|2016-06-30|BONE SUBSTITUTE AND AUTONOMOUS INJECTION SYSTEM|FR1656231A| FR3053239B1|2016-06-30|2016-06-30|BONE SUBSTITUTE AND AUTONOMOUS INJECTION SYSTEM|
    US16/314,111| US11141206B2|2016-06-30|2017-06-30|Bone substitute and independent injection system|
    KR1020197002174A| KR102343181B1|2016-06-30|2017-06-30|Bone substitutes and independent injection systems|
    JP2018568790A| JP2019521767A|2016-06-30|2017-06-30|Bone replacement material and stand-alone injection system|
    CN201780045751.7A| CN109803613B|2016-06-30|2017-06-30|Bone substitute and independent injection system|
    EP17732963.8A| EP3478225A1|2016-06-30|2017-06-30|Bone substitute and independent injection system|
    BR112018077374A| BR112018077374A2|2016-06-30|2017-06-30|bone substitute and autonomous injection system|
    PCT/EP2017/066346| WO2018002335A1|2016-06-30|2017-06-30|Bone substitute and independent injection system|
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