WO2011070189A1 - Implant osseux pourvu de côtés poreux pour la libération contrôlée de composés thérapeutiquement actifs - Google Patents

Implant osseux pourvu de côtés poreux pour la libération contrôlée de composés thérapeutiquement actifs Download PDF

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Publication number
WO2011070189A1
WO2011070189A1 PCT/ES2010/000500 ES2010000500W WO2011070189A1 WO 2011070189 A1 WO2011070189 A1 WO 2011070189A1 ES 2010000500 W ES2010000500 W ES 2010000500W WO 2011070189 A1 WO2011070189 A1 WO 2011070189A1
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WIPO (PCT)
Prior art keywords
therapeutically active
release
porous
implant
primary chamber
Prior art date
Application number
PCT/ES2010/000500
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English (en)
Spanish (es)
Inventor
Manuel Arruebo Gordo
Silvia Irusta Alderete
Luis Manuel Perez Puentes
Patricia Lalueza Valero
José Antonio PUERTOLAS RAFAEL
Luis Gracia Villa
Felicito Enrique GARCIA-ÁLVAREZ GARCIA
Marta Monzon Garces
Jesús SANTAMARIA RAMIRO
Original Assignee
Universidad De Zaragoza
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Application filed by Universidad De Zaragoza filed Critical Universidad De Zaragoza
Publication of WO2011070189A1 publication Critical patent/WO2011070189A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/28—Bones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/16—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0092—Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1611—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/54—Biologically active materials, e.g. therapeutic substances
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
    • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L27/56—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
    • A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
    • A61L31/146—Porous materials, e.g. foams or sponges
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
    • A61B17/56—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor
    • A61B2017/561—Implants with special means for releasing a drug
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30108—Shapes
    • A61F2002/30199—Three-dimensional shapes
    • A61F2002/30224—Three-dimensional shapes cylindrical
    • A61F2002/30235—Three-dimensional shapes cylindrical tubular, e.g. sleeves
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2002/30001—Additional features of subject-matter classified in A61F2/28, A61F2/30 and subgroups thereof
    • A61F2002/30667—Features concerning an interaction with the environment or a particular use of the prosthesis
    • A61F2002/30677—Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body
    • A61F2002/3068—Means for introducing or releasing pharmaceutical products, e.g. antibiotics, into the body the pharmaceutical product being in a reservoir
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2/00—Filters implantable into blood vessels; Prostheses, i.e. artificial substitutes or replacements for parts of the body; Appliances for connecting them with the body; Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents
    • A61F2/02—Prostheses implantable into the body
    • A61F2/30—Joints
    • A61F2/30767—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth
    • A61F2002/3092—Special external or bone-contacting surface, e.g. coating for improving bone ingrowth having an open-celled or open-pored structure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2230/00—Geometry of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2230/0063—Three-dimensional shapes
    • A61F2230/0069—Three-dimensional shapes cylindrical
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
    • A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
    • A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
    • A61F2250/0067—Means for introducing or releasing pharmaceutical products into the body
    • A61F2250/0068—Means for introducing or releasing pharmaceutical products into the body the pharmaceutical product being in a reservoir
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
    • A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • A61L2300/406—Antibiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2430/00—Materials or treatment for tissue regeneration
    • A61L2430/02—Materials or treatment for tissue regeneration for reconstruction of bones; weight-bearing implants

Definitions

  • the present invention can be included in the technical field of the development of implants, screws, scaffolds, fixings, etc. employees in traumatology and orthopedic surgery.
  • the present invention can also be included in the technical field of the administration of therapeutically active compounds, in particular in the administration from the inside of the body in a controlled manner of drugs or any therapeutically active substance.
  • the object of the present invention is a bone implant, provided with porous limits, for the controlled release of therapeutically active compounds, for use in traumatology and orthopedic surgery, adapted to release a therapeutically active compound contained therein in a controlled manner and Lasting over time.
  • the Journal of Controlled Relay 2005, number 102, pages 123-133 describes a device or implant provided with a nanoporous membrane. It comprises a cylindrical methacrylate carrier equipped with two rubber rings. A nanoporous membrane of 2x3 mm. It is fixed on a small hole that passes through the carrier by means of general purpose silicone that is allowed to cure at 55 Q C for 3 hours to achieve its fixation. The entire carrier is inserted into a titanium container until the membrane is fully aligned.
  • methacrylate lids are sealed, containing releasable rubber septum, using silicone adhesive and allowed to cure.
  • the implant is oriented vertically, and a 27-gauge Luer-Lock needle is inserted into the upper septum for use as an air inlet.
  • a pharmacological liquid suspension is slowly injected into the implant through the lower septum until all the air inside the implant is removed, as indicated by fluid exudation from the needle. Needles are removed under pressure to prevent air ingress.
  • the implants are rinsed by immersion before being placed in a control vessel or during surgical implantation.
  • implants or other perforated mechanical models that release a drug previously encapsulated in a polymer are known.
  • bone growth is described in vivo by means of a titanium implant with TGF- ⁇ release.
  • a porous titanium implant was developed.
  • encapsulated placebo or TGF- ⁇ were placed in a negative pressure jelly sponge and placed in the porous titanium implant for unicortical implantation in the humerus of a rabbit.
  • Porous matrices that release an encapsulated drug therein are also known, as can be seen from the Journal of the Chemical Society, Dalton Translations, 2006, pages 521 1-5220.
  • the technical problem to be solved is to describe a bone implant provided with porous limits for the release of a therapeutically active compound capable of releasing said pharmacological compound that is contained within it in a controlled and lasting manner.
  • the present invention solves the technical problem posed by means of a bone implant provided with porous limits for the controlled release of a therapeutically active compound, preferably a percutaneous screw or a centromedular nail, comprising a hollow carrier, preferably in a cylindrical shape, manufactured in a porous material, or at least with some porous areas, preferably a metal suitable for implantation inside a human or animal body, such as steel or titanium, for example.
  • a therapeutically active compound preferably a percutaneous screw or a centromedular nail
  • a hollow carrier preferably in a cylindrical shape, manufactured in a porous material, or at least with some porous areas, preferably a metal suitable for implantation inside a human or animal body, such as steel or titanium, for example.
  • a filling material is arranged inside the carrier.
  • the filler material is a nanoporous inorganic silica material of ordered pores, preferably the same.
  • the filler material consists of both a fixed bed composed of microparticles and a continuous membrane-like film.
  • An example of nanoporous material is mesoporous silica, preferably one of the materials selected from MCM-41, MCM-48, and SBA-15. Said filling material partially occupies the interior space of the carrier, called the primary chamber.
  • a therapeutically active compound is adsorbed, such as a drug, a protein, a plasmid, etc.
  • a drug is especially preferred.
  • a preferred type of pharmacological compound capable of being adsorbed in said pores is antibiotics, for example Linezolid (Zyvoxid ®).
  • the implant of the present invention Through the use of the implant of the present invention, an exhaustive control of the release profile of the therapeutically active compound contained is achieved, because there are two physical barriers to the release of the therapeutically active compound. Indeed, the therapeutically active compound particles adsorbed in the pores of the mesoporous filler material are first released into the primary chamber by diffusion and then accessed through the pores of the carrier's porous wall into the bloodstream .
  • the kinetic process that regulates the release of the therapeutically active compound particles into the primary chamber depends on the characteristics of the particles (diameter, porosity, packing density), as well as on the concentration of said particles within the primary chamber
  • the kinetics of the outward release of the primary chamber depends on the concentration on both sides of the porous wall of the carrier, and on the characteristics of said porous wall of the carrier, such as permeation area, thickness, porosity.
  • the advantage of having the therapeutically active compound adsorbed inside the pores of the filler material (intra distribution) with respect to the distribution between the pores (inter distribution) is related to the need to protect the therapeutically active compound against the degradation by chemical or enzymatic action (nucleases, proteases, etc.), as well as with the need to minimize the incidence of sudden release (burst relée) that is often associated with adsorbed compounds on the external surface of materials.
  • the fact of selecting fillers with ordered pores allows a better control of the release process, with respect to the situation in which the material has a wide distribution.
  • the degradation of a biodegradable organic material is via erosion of the matrix and, therefore, the release profiles are difficult to reproduce. Since the invention does not contemplate the use of biodegradable materials, the encapsulating matrix (the carrier) remains unchanged in the processes of loading therapeutically active compound into the filler material and releasing said therapeutically active material.
  • the invention allows different sizes of carriers and, therefore, of bone implants to be released for the release of the therapeutically active compound, depending on the dose of therapeutically active compound necessary in each case.
  • the carrier comprises a porous part and a non-porous part, there being in the non-porous part a window sealed with a nanoporous inorganic material, preferably with zeolite.
  • This window is in contact with the primary chamber. From said primary chamber the therapeutically active compound can be diffused out of the carrier through the sealed window, according to a controlled release.
  • Figure 1. Shows a longitudinal sectional view of the first embodiment of the invention.
  • Figure 2. Shows an enlarged view of the interior of the filler material where the pores and the therapeutically active compound particles adsorbed in said pores are appreciated.
  • Figure 3. Shows the release of a hospital solution (line
  • Figure 4. Shows the release of linezolid® (line B) from a bed of MCM48 filler material.
  • Figure 5. Shows the difference between the release of linezolid® from a carrier loaded with hospital solution (line A) and from a carrier loaded with a set of filler material plus drug (line A).
  • Figure 6. Shows a comparison between the concentrations of linezolid® reached by 400 nm particles. (line C1) with respect to 1500 nm particles. (line D1) in 50 mi. from SBF to 37 Q C.
  • Figure 7. Shows a comparison between linezolid® flows from 400 nm particles. (C2) and 1500 nm. (D2) in 50 mi. from SBF to 37
  • Figure 8. Shows a comparison of four of the forms of release studied (lines A, B, C1 and D1).
  • Figure 9.- Shows a longitudinal sectional view of the third embodiment of the invention.
  • a bone implant (1) for the release of a therapeutically active compound (5), according to a percutaneous screw is described with the aid of Figures 1 and 2.
  • the implant (1) comprises a steel carrier (2) in the form of a hollow cylinder, with a porous wall (6) in which a primary chamber (3) is defined.
  • a bed of filler material (4) of the MCM-41 mesoporous silica type is distributed, with pores (7) (see Figure 2) ordered and equal in nanometric size.
  • a therapeutically active compound (5) of the drug type is adsorbed, which can be released by diffusion from the filler material (4) to the primary chamber (3) in a first step, and outward from the primary chamber (3) through the porous wall (6) of the carrier (2).
  • the factors that regulate the diffusion between the filler material (5) and the primary chamber (3) are the diameter of the particles of therapeutically active compound (5), as well as the diameter of the pores (7) and the density of packing of the filling material (4), in addition to the concentration of said particles inside the primary chamber (3).
  • the factors that regulate the release of the therapeutically active compound particles (5) through the porous wall (4) are the concentration of said particles on both sides of the porous wall (6) and the characteristics of said wall (6) porous, such as permeation area, thickness and porosity of the porous wall material (6).
  • the invention allows the control of diffusion to the primary chamber (3) and of the release through the porous wall (6) independently, providing a control of the release profile more customized to the needs of each specific case.
  • the results of a drug release (5) arranged directly in solution inside a carrier (2) are compared with respect to a release using a filler material (3) in which the drug is adsorbed ( 5).
  • the experimental system used for the study of drug release (5) comprises:
  • the filler material (4) used is mesoporous silica type MCM-48.
  • the carrier (2) with the hospital solution or with the filling material set is mesoporous silica type MCM-48.
  • Line B in the figure shows the release of drug (5) from a filler material (4) MCM-48 previously loaded with linezolid®.
  • the filler material (4) is previously contacted with the hospital solution, the pores (7) of the stuffed material of said drug (5) remaining. 37.6 mg are introduced into the carrier (2). with 6.17% by weight of linezolid®.
  • Figure 5 shows an example illustrating the difference in drug release (5) from a carrier (2) loaded with hospital solution (line A) and from another carrier (2) loaded with the filling material set (4) plus drug (5) (line B).
  • linezolid® As seen in view of Figure 5, it has been possible to slow down the release of linezolid® only by adsorbing it in a bed of mesoporous filler material (4).
  • the release profile and kinetics of the pre-adsorbed drug (5) in said porous filler material (4) have been achieved.
  • FIG 9 shows a sectional view of the third preferred embodiment, where a bone implant (1) can be seen for the release of a therapeutically active compound (5), (see figure 2).
  • the implant (1) comprises a steel carrier (2) in the form of a hollow cylinder, inside which a primary chamber (3) is defined.
  • a bed of filler material (4) of the MCM-41 mesoporous silica type is distributed, with pores (7) (see Figure 2) ordered and equal in nanometric size.
  • the carrier (2) has a wall (6) in which there is a window (8) that communicates with the primary chamber (3). Said window (8) is sealed with a zeolite membrane (9). Inside the pores (7) of the filler material (4) a therapeutically active compound (5) of the drug type is adsorbed, which can be released by diffusion from the filler material (4) to the primary chamber (3 ) in a first step, and outwards of the primary chamber (3) through the membrane (9).

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Dermatology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dispersion Chemistry (AREA)
  • Molecular Biology (AREA)
  • Inorganic Chemistry (AREA)
  • Surgery (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Cardiology (AREA)
  • Nanotechnology (AREA)
  • Neurosurgery (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Materials For Medical Uses (AREA)

Abstract

L'invention concerne un implant osseux qui comprend un support (2) creux, et une paroi (6) présentant au moins une certaine zone poreuse qui définit à l'intérieur dudit support (2) une chambre primaire (3), dans Iaquelle est présente une matière de remplissage (4) présentant des pores (7) égaux et ordonnés dans lesquels sont absorbées des particules d'un médicament (5). Les particules du médicament (5) sont libérées vers l'extérieur tout d'abord par diffusion à partir des pores (7) de la matière de remplissage (4) vers la chambre primaire (4) et ensuite à partir de la chambre primaire (3) vers l'extérieur à travers la paroi (6) poreuse, ce qui permet d'obtenir un double contrôle du profil de libération du médicament (5).
PCT/ES2010/000500 2009-12-11 2010-12-09 Implant osseux pourvu de côtés poreux pour la libération contrôlée de composés thérapeutiquement actifs WO2011070189A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
ESP200931157 2009-12-11
ES200931157A ES2362228B1 (es) 2009-12-11 2009-12-11 Implante en hueso, dotado de limites porosos para la liberación controlada de compuestos terapéuticamente activos.

Publications (1)

Publication Number Publication Date
WO2011070189A1 true WO2011070189A1 (fr) 2011-06-16

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PCT/ES2010/000500 WO2011070189A1 (fr) 2009-12-11 2010-12-09 Implant osseux pourvu de côtés poreux pour la libération contrôlée de composés thérapeutiquement actifs

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ES (1) ES2362228B1 (fr)
WO (1) WO2011070189A1 (fr)

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050171593A1 (en) * 2004-01-30 2005-08-04 Trivascular, Inc. Inflatable porous implants and methods for drug delivery
US20060093646A1 (en) * 2004-10-28 2006-05-04 Cima Michael J Orthopedic and dental implant devices providing controlled drug delivery
US20080145400A1 (en) * 2006-11-03 2008-06-19 Jan Weber Ion Bombardment of Medical Devices
US20080188836A1 (en) * 2007-02-02 2008-08-07 Boston Scientific Scimed, Inc. Medical devices having nanoporous coatings for controlled therapeutic agent delivery
WO2009021209A2 (fr) * 2007-08-09 2009-02-12 The Board Of Regents Of The University Of Texas System Charpente de type osseux à deux couches

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050171593A1 (en) * 2004-01-30 2005-08-04 Trivascular, Inc. Inflatable porous implants and methods for drug delivery
US20060093646A1 (en) * 2004-10-28 2006-05-04 Cima Michael J Orthopedic and dental implant devices providing controlled drug delivery
US20080145400A1 (en) * 2006-11-03 2008-06-19 Jan Weber Ion Bombardment of Medical Devices
US20080188836A1 (en) * 2007-02-02 2008-08-07 Boston Scientific Scimed, Inc. Medical devices having nanoporous coatings for controlled therapeutic agent delivery
WO2009021209A2 (fr) * 2007-08-09 2009-02-12 The Board Of Regents Of The University Of Texas System Charpente de type osseux à deux couches

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ES2362228B1 (es) 2013-06-03

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