WO2002004038A1 - Active biocoating for bone implant - Google Patents

Active biocoating for bone implant Download PDF

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Publication number
WO2002004038A1
WO2002004038A1 PCT/CH2000/000382 CH0000382W WO0204038A1 WO 2002004038 A1 WO2002004038 A1 WO 2002004038A1 CH 0000382 W CH0000382 W CH 0000382W WO 0204038 A1 WO0204038 A1 WO 0204038A1
Authority
WO
WIPO (PCT)
Prior art keywords
implant
bone
active agent
fact
layer
Prior art date
Application number
PCT/CH2000/000382
Other languages
French (fr)
Inventor
Dominique Pioletti
Lalaonirina Rakotomanana Ravelonarivo
Original Assignee
Hopital Orthopedique De La Suisse Romande
Ecole Polytechnique Federale De Lausanne (Epfl)
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hopital Orthopedique De La Suisse Romande, Ecole Polytechnique Federale De Lausanne (Epfl) filed Critical Hopital Orthopedique De La Suisse Romande
Priority to AU2001287260A priority Critical patent/AU2001287260A1/en
Priority to PCT/CH2000/000382 priority patent/WO2002004038A1/en
Publication of WO2002004038A1 publication Critical patent/WO2002004038A1/en

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Classifications

    • 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
    • A61L27/28—Materials for coating prostheses
    • A61L27/30—Inorganic materials
    • A61L27/32—Phosphorus-containing materials, e.g. apatite
    • 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
    • A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
    • A61L2300/216—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with other specific functional groups, e.g. aldehydes, ketones, phenols, quaternary phosphonium groups
    • 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
    • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
    • A61L2300/606—Coatings
    • 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 relates to bone implant.
  • this invention relates to a bone implant coated with a layer which releases an active agent controlling the bone remodeling.
  • This kind of implant can be used for a total joint replacement, where it is observed following the procedure a marked phenomena of osteolysis in the peri-implant zone. This bone tissue resorption can considerably decrease the efficiency of the implant necessitating generally to proceed a revision surgery.
  • US patent No. 5 972 913 discloses an implant coated which a layer delivering progressively a dose of bisphosphonate in order to control the bone resorption in the peri-implant zone.
  • bisphosphonates act as inhibitors of the bone resorption. Their progressive release at the implant surface enables to slow the bone resorption in the peri-implant zone.
  • the bone resorption in the peri- implant zone is not uniform. Some zones present a marked bone resorption while others, where the mechanical stress is important, present an important bone formation. This means that a uniform coating of the active agent on the implant will considerably reduce its efficiency. In some situations, the controlling of bone resorption with an active agent biocoating can be as much or even more detrimental as in situations where the implant is not coated with an active agent.
  • the present invention aims to remedy among others, the previously described problems.
  • This invention refers to an implant releasing an active agent which influences the bone remodeling, the implant being partially coated with a layer comprising the active agent.
  • the coated zones are located in peri-implant zones where the bone remodeling has to be controlled.
  • the inventors of the present invention have surprisingly noted that a partial coating of the implant with an active agent that influences the bone remodeling, in particular with a bisphosphonate, can result in a significant decrease of the bone resorption in the peri-implant zones. In all cases, the decrease of bone resorption with a partial coating of the implant was more marked than the bone resorption observed with an implant completely coated with the active agent.
  • the zones coated with the active agent are determined by means of a model representing the bone remodeling in the peri-implant environment.
  • model which may be used for the present invention
  • the model uses constant values experimentally determined, which define the rate of bone resorption and formation.
  • the active agent used can be chosen among all substances acting on the bone remodeling.
  • the active agent is a bisphosphonate.
  • bisphosphonate it can be cited the one described in US patent No. 5 972 913 or the ZolendronateTM from the company Novartis.
  • the implant is partially coated with an hydroxyapatite layer on which the active agent is superposed.
  • a particularly advantageous configuration of the invention is the coating of the implant with hydroxyapatite on which a bisphosphonate layer is superposed.
  • Figure 1 illustrates the bone density distribution of a femur at the time of implantation of a hip prosthesis.
  • Figure 2 illustrates the bone density distribution of the femur of figure 1 following the bone adaptation corresponding to two years post-operatively.
  • Figure 3 illustrates the bone density distribution of the femur of figure 1 following the bone adaptation corresponding to two years post-operatively when the implant is completely coated with the active agent.
  • Figure 4 illustrates the bone density distribution of the femur of figure 1 following the bone adaptation corresponding to two years post-operatively when the implant is partially coated with the active agent.
  • a low bone density is represented by a color tending to white
  • a high bone density is represented by a color tending to black.
  • the color gray indicates zones where bone density has slightly changedwith respect to the initial bone density measured at the time of prosthesis implantation.
  • the femur shown on figure 1 together with its bone density have been reconstructed from CT-scan images.
  • the inserted prosthesis is neither shown in this figure nor in the others.
  • the figures 2 to 4 represent each time the bone remodeling of the same femur of figure 1 two years after the insertion of the prosthesis.
  • the figure 2 represents the bone density of the femur whose implant had no bioactive coating. We note in this case a marked bone resorption in the proximal part of the femur, which can lead to an aseptic loosening of the implant.
  • the figure 4 illustrates the situation in accordance with the invention where the prosthesis has been coated only in its proximal portion. It clearly emerges that the partial coating enables to strongly decrease the bone resorption. In examples not illustrated in the present text, an optimal bone remodeling has been observed by coating the prosthesis on zones of bone resorption observed on the figure 2.
  • the invention is not limited to the coating of the prosthesis at a precise position. It should be understood that the invention relates to a partial coating of a prosthesis by an active agent to control notably the bone remodeling in the peri-implant environment.

Abstract

This invention relates to a bone implant coated with a layer which releases an active agent in order to control the bone remodeling.

Description

Active biocoating for bone implant
The present invention relates to bone implant.
More specifically, this invention relates to a bone implant coated with a layer which releases an active agent controlling the bone remodeling.
This kind of implant can be used for a total joint replacement, where it is observed following the procedure a marked phenomena of osteolysis in the peri-implant zone. This bone tissue resorption can considerably decrease the efficiency of the implant necessitating generally to proceed a revision surgery.
In the United States of America, it is estimated that such revision surgery costs more than two billions dollars per year.
US patent No. 5 972 913 discloses an implant coated which a layer delivering progressively a dose of bisphosphonate in order to control the bone resorption in the peri-implant zone.
It is indeed known that bisphosphonates act as inhibitors of the bone resorption. Their progressive release at the implant surface enables to slow the bone resorption in the peri-implant zone.
Prior art bone implants such as the ones described in US patent No. 5 972 913, present however several drawbacks.
During their carrying out, it is not taken into account that the bone resorption in the peri- implant zone is not uniform. Some zones present a marked bone resorption while others, where the mechanical stress is important, present an important bone formation. This means that a uniform coating of the active agent on the implant will considerably reduce its efficiency. In some situations, the controlling of bone resorption with an active agent biocoating can be as much or even more detrimental as in situations where the implant is not coated with an active agent.
The present invention aims to remedy among others, the previously described problems.
This invention refers to an implant releasing an active agent which influences the bone remodeling, the implant being partially coated with a layer comprising the active agent. The coated zones are located in peri-implant zones where the bone remodeling has to be controlled. The inventors of the present invention have surprisingly noted that a partial coating of the implant with an active agent that influences the bone remodeling, in particular with a bisphosphonate, can result in a significant decrease of the bone resorption in the peri-implant zones. In all cases, the decrease of bone resorption with a partial coating of the implant was more marked than the bone resorption observed with an implant completely coated with the active agent.
In accordance with a preferred embodiment, the zones coated with the active agent are determined by means of a model representing the bone remodeling in the peri-implant environment.
As example of model which may be used for the present invention, we can cite the model described in the article of A. Terrier, L. Rakotomanana, N. Ramaniraka, and P.F. Leyvraz "Adaptation models of anisotropic bone", Computer Methods in Biomechanics and Biomedical Engineering, vol. 1 , pp. 47-59, 1997.
In a variant of the invention, the model uses constant values experimentally determined, which define the rate of bone resorption and formation. The active agent used can be chosen among all substances acting on the bone remodeling.
Preferably, the active agent is a bisphosphonate.
By way of example of bisphosphonate, it can be cited the one described in US patent No. 5 972 913 or the Zolendronate™ from the company Novartis.
In another embodiment the implant is partially coated with an hydroxyapatite layer on which the active agent is superposed.
A particularly advantageous configuration of the invention is the coating of the implant with hydroxyapatite on which a bisphosphonate layer is superposed.
In the following text, the invention will be described by means of illustrated examples on the following figures:
Figure 1 illustrates the bone density distribution of a femur at the time of implantation of a hip prosthesis.
Figure 2 illustrates the bone density distribution of the femur of figure 1 following the bone adaptation corresponding to two years post-operatively.
Figure 3 illustrates the bone density distribution of the femur of figure 1 following the bone adaptation corresponding to two years post-operatively when the implant is completely coated with the active agent.
Figure 4 illustrates the bone density distribution of the femur of figure 1 following the bone adaptation corresponding to two years post-operatively when the implant is partially coated with the active agent. On each figure, a low bone density is represented by a color tending to white, while a high bone density is represented by a color tending to black. The color gray indicates zones where bone density has slightly changedwith respect to the initial bone density measured at the time of prosthesis implantation.
The femur shown on figure 1 together with its bone density have been reconstructed from CT-scan images. The inserted prosthesis is neither shown in this figure nor in the others.
A numerical simulation was then performed taking into account loading conditions simulating a loading on one leg (weight and muscles forces) and using the model of A. Terrier, L. Rakotomanana, N. Ramaniraka, and P.F. Leyvraz described in the previously cited article.
The figures 2 to 4 represent each time the bone remodeling of the same femur of figure 1 two years after the insertion of the prosthesis.
The figure 2 represents the bone density of the femur whose implant had no bioactive coating. We note in this case a marked bone resorption in the proximal part of the femur, which can lead to an aseptic loosening of the implant.
A similar situation can be observed on figure 3 where the prosthesis had been completely coated on its surface with a bisphosphonate. We note more precisely that the biocoating decreases only slightly the proximal bone resorption and has therefore no significant effect in comparison with the situation of an implant without an active agent coating.
The figure 4 illustrates the situation in accordance with the invention where the prosthesis has been coated only in its proximal portion. It clearly emerges that the partial coating enables to strongly decrease the bone resorption. In examples not illustrated in the present text, an optimal bone remodeling has been observed by coating the prosthesis on zones of bone resorption observed on the figure 2.
Of course, the invention is not limited to the coating of the prosthesis at a precise position. It should be understood that the invention relates to a partial coating of a prosthesis by an active agent to control notably the bone remodeling in the peri-implant environment.

Claims

Claims
1. Bone implant releasing an active agent which influences the bone remodeling, characterized by the fact that it is partially coated with a layer containing the said active agent, said layer being situated in peri-implant zones where the bone remodeling has to be controlled.
2. Implant according to claim 1 , characterized by the fact that the position of said layer is determined by means of a model which represents the bone remodeling in a peri-implant environment.
3. Implant according to claim 2, characterized by the fact that the model uses constant values, determined experimentally, which define the rate of bone resorption and formation.
4. Implant according to any of the previous claim, characterized by the fact that active agent is a bisphosphonate.
5. Implant according to any of the previous claim, characterized by the fact that it is coated with a layer of hydroxyapatite on which the active agent is superposed.
6. Implant according to claim 5, characterized by the fact that the active agent is a bisphosphonate.
PCT/CH2000/000382 2000-07-12 2000-07-12 Active biocoating for bone implant WO2002004038A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU2001287260A AU2001287260A1 (en) 2000-07-12 2000-07-12 Active biocoating for bone implant
PCT/CH2000/000382 WO2002004038A1 (en) 2000-07-12 2000-07-12 Active biocoating for bone implant

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/CH2000/000382 WO2002004038A1 (en) 2000-07-12 2000-07-12 Active biocoating for bone implant

Publications (1)

Publication Number Publication Date
WO2002004038A1 true WO2002004038A1 (en) 2002-01-17

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WO (1) WO2002004038A1 (en)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005018699A1 (en) * 2003-08-21 2005-03-03 Optovent Ab Bisphosphonate coated implant device and method therefor
WO2007048263A2 (en) 2005-10-27 2007-05-03 Nexilis Ag Implant and production method for said implant
WO2007048264A1 (en) 2005-10-27 2007-05-03 Thommen Medical Ag Dental implant and production method for said implant
US8882740B2 (en) 2009-12-23 2014-11-11 Stryker Trauma Gmbh Method of delivering a biphosphonate and/or strontium ranelate below the surface of a bone
US10045798B2 (en) 2012-11-11 2018-08-14 Carbofix Orthopedics Ltd. Composite implant coating

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994023770A1 (en) * 1993-04-14 1994-10-27 Leiras Oy A method of treating endo-osteal materials
WO1995030421A1 (en) * 1994-05-04 1995-11-16 Ciba-Geigy Ag Use of certain methanebisphosphonic acid derivatives to prevent prosthesis loosening and prosthesis migration
WO1996039107A1 (en) * 1995-06-06 1996-12-12 Merck & Co., Inc. Bisphosphonate cement composition to prevent aseptic loosening of orthopedic implant devices
WO1997029754A1 (en) * 1996-02-14 1997-08-21 Itzhak Binderman Topical bisphosphonates for prevention of bone resorption
US5972913A (en) * 1994-04-21 1999-10-26 Merck & Co., Inc. Alendronate therapy to prevent loosening of, or pain associated with, orthopedic implant devices
WO2000033849A1 (en) * 1998-12-04 2000-06-15 Roche Diagnostics Gmbh Use of ibandronate for promoting osseointegration of endoprostheses

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994023770A1 (en) * 1993-04-14 1994-10-27 Leiras Oy A method of treating endo-osteal materials
US5972913A (en) * 1994-04-21 1999-10-26 Merck & Co., Inc. Alendronate therapy to prevent loosening of, or pain associated with, orthopedic implant devices
WO1995030421A1 (en) * 1994-05-04 1995-11-16 Ciba-Geigy Ag Use of certain methanebisphosphonic acid derivatives to prevent prosthesis loosening and prosthesis migration
WO1996039107A1 (en) * 1995-06-06 1996-12-12 Merck & Co., Inc. Bisphosphonate cement composition to prevent aseptic loosening of orthopedic implant devices
WO1997029754A1 (en) * 1996-02-14 1997-08-21 Itzhak Binderman Topical bisphosphonates for prevention of bone resorption
WO2000033849A1 (en) * 1998-12-04 2000-06-15 Roche Diagnostics Gmbh Use of ibandronate for promoting osseointegration of endoprostheses

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
SHANBHAG A S ET AL: "BISPHOSPHONATE THERAPY FOR THE PREVENTION OF OSTEOLYSIS IN TOTAL JOINT REPLACEMENTS", CURRENT OPINION IN ORTHOPAEDICS,US,CURRENT SCIENCE, PHILADELPHIA, PA, vol. 9, no. 6, December 1998 (1998-12-01), pages 81 - 87, XP000892667, ISSN: 1041-9918 *
WALL A ET AL: "AUSWERTUNG DER OSTEOINTEGRATION VON ZEMENTLOSEN HUEFTPROTHESENSTIELEN MIT COMPUTERAUSWERTUNG DIGITALER ROENTGENDENSITOMETRIE", ORTHOPAEDISCHE PRAXIS,DE,MEDIZINISCHE LITERARISCHE VERLAGSGESELLSCHAFT, UELZEN, vol. 34, no. 2, February 1998 (1998-02-01), pages 73 - 77, XP000892809, ISSN: 0030-588X *

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005018699A1 (en) * 2003-08-21 2005-03-03 Optovent Ab Bisphosphonate coated implant device and method therefor
JP2007533345A (en) * 2003-08-21 2007-11-22 オプトヴェント・アクチボラゲット Bisphosphonate-coated implant device and method therefor
CN1871038B (en) * 2003-08-21 2010-10-06 艾德拜奥股份有限公司 Bisphosphonate coated implant device and method therefor
WO2007048263A2 (en) 2005-10-27 2007-05-03 Nexilis Ag Implant and production method for said implant
WO2007048264A1 (en) 2005-10-27 2007-05-03 Thommen Medical Ag Dental implant and production method for said implant
JP2009513197A (en) * 2005-10-27 2009-04-02 トーメン メディカル アーゲー Dental implant and manufacturing method thereof
US8940320B2 (en) 2005-10-27 2015-01-27 Thommen Medical Ag Dental implant and production method for said implant
US8882740B2 (en) 2009-12-23 2014-11-11 Stryker Trauma Gmbh Method of delivering a biphosphonate and/or strontium ranelate below the surface of a bone
US10045798B2 (en) 2012-11-11 2018-08-14 Carbofix Orthopedics Ltd. Composite implant coating
US10687864B2 (en) 2012-11-11 2020-06-23 Carbofix In Orthopedics Llc Composite implant coating

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