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WO2003059409A2 - Materiaux d'implant biodegradables - Google Patents

Materiaux d'implant biodegradables Download PDF

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Publication number
WO2003059409A2
WO2003059409A2 PCT/GB2002/005860 GB0205860W WO03059409A2 WO 2003059409 A2 WO2003059409 A2 WO 2003059409A2 GB 0205860 W GB0205860 W GB 0205860W WO 03059409 A2 WO03059409 A2 WO 03059409A2
Authority
WO
WIPO (PCT)
Prior art keywords
material according
filler
anhydrite
polymer
soluble
Prior art date
Application number
PCT/GB2002/005860
Other languages
English (en)
Other versions
WO2003059409A3 (fr
Inventor
John Joseph Cooper
Original Assignee
Biocomposites Limited
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 Biocomposites Limited filed Critical Biocomposites Limited
Priority to AU2002366969A priority Critical patent/AU2002366969A1/en
Publication of WO2003059409A2 publication Critical patent/WO2003059409A2/fr
Publication of WO2003059409A3 publication Critical patent/WO2003059409A3/fr

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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
    • 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
    • A61L31/148—Materials at least partially resorbable by the body
    • 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
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A61L24/0042—Materials resorbable by the body
    • 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
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/0047—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L24/0073—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material with a macromolecular matrix
    • A61L24/0089—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material with a macromolecular matrix containing inorganic fillers not covered by groups A61L24/0078 or A61L24/0084
    • 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
    • A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L27/446—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with other specific inorganic fillers other than those covered by A61L27/443 or A61L27/46
    • 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
    • A61L27/58—Materials at least partially resorbable by the body
    • 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
    • A61L31/12—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
    • A61L31/125—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
    • A61L31/128—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix containing other specific inorganic fillers not covered by A61L31/126 or A61L31/127

Definitions

  • This invention concerns biodegradable implant materials, and particularly but not exclusively biodegradable implant materials suitable for medical uses such as bone grafting or bone fixation procedures.
  • implant materials are synthetically derived in order to overcome some of the difficulties and potential problems reported to be associated with allograft or autograft tissue.
  • synthetic inorganic materials generally comprise either hydroxyapatite, tri-calcium phosphate or calcium sulphate dihydrate.
  • thermoplastic bioabsorbable polymers Many devices for application at a bony site within the body are manufactured from thermoplastic bioabsorbable polymers. These materials offer a number of advantages over traditional metallic devices including; no stress shielding effects; no long term metal ion release, no interference with MRJ imaging techniques and no need to remove the implant in a further surgical procedure.
  • the main mechanism for degradation of this class of polymer within the bddy is by hydrolysis.
  • the rate of degradation and loss in strength of the polymer can be tailored to suit the clinical indication.
  • Thermoplastic polymers can be processed into complex net-shaped components in an efficient and cost effective manner by techniques such as injection moulding.
  • bio-ceramic fillers can be introduced to give biocomposite materials with properties more appropriate to the clinical need than the polymers or copolymers alone.
  • the fillers may comprise bioactive materials, such as hydroxyapatite (HA) or beta tri-calcium phosphate ( ⁇ -TCP) in particulate form, which can confer a number of advantages. These materials are osteoconductive and can give the potential for bony in-fill to the surgical site once the polymeric component has been bioabsorbed.
  • a filler in a polymer increases its flexural and Youngs modulus such that modulus matching to bone becomes possible.
  • the presence of the filler also imparts a measure of X-ray density to the material which makes imaging a little easier. It has also been demonstrated that these materials present as fillers can provide a buffering action to the acidic degradation products of the polymer, helping to minimise any acidosis effects within the body.
  • HA hydroxyapatite
  • ⁇ TCP beta tri-calcium phosphate
  • CS calcium sulphate
  • Beta tri-calcium phosphate is practically insoluble, however within the body at a bony site it is slowly resorbed over a period of several months primarily by cell mediated processes and provides an environment for new bone formation.
  • these materials can only become bio-absorbed themselves once the polymer component has started to degrade, resorb and become porous to such an extent that the body's cells have access to said filler component. This process can take many years for the higher strength and higher molecular weight polymers currently used for bony site fixation applications.
  • Calcium sulphate is used as a bone graft material either in the form of pellets/granules of gypsum (CaS0 . 2 H 2 0) or as plaster of paris (CaS0 4 l A H 2 0) which is mixed with water or saline to form a paste which subsequently hardens and sets as gypsum.
  • gypsum pellets/granules of gypsum
  • CaS0 4 l A H 2 0 plaster of paris
  • These materials are soluble in water and within the body they are bio-absorbed by a simple dissolution mechanism over a period of 30-60 days. This can be considered to be rather rapid for some applications in a bony site since it is faster than the rate at which new bone can form.
  • the main problem with the use of the soluble anhydrite as a bioactive filler for a thermoplastic bioabsorbable polymer in a load bearing application is that as water from bodily fluids diffuses into the composite matrix the calcium sulphate solubilises and diffuses out thus leaving pores within the polymer. This occurs in a time period which is short compared to the rate of bony union and to the rate at which the polymer is designed to degrade.
  • the formation of porosity within the polymer is accompanied by a rapid fall in both strength and modulus and hence the polymers ability to maintain mechanical integrity to the healing bone, obviously a major drawback in a load-bearing application.
  • calcium sulphate in the form of gypsum, plaster of paris or soluble anhydrite can give an acidic response when immersed in water, which would contribute to the acidosis effect sometimes reported to be associated with certain bioresorbable polymers.
  • a biodegradable implant material comprising anhydrous calcium sulphate.
  • the material may also comprise bioabsorbable polymer.
  • the material may also comprise a bioabsorbable calcium phosphate material.
  • the material is preferably degradable in a body in a similar time frame to the rate at which new bone can form.
  • the anhydrous calcium sulphate may be in the form of soluble or insoluble anhydrite.
  • the implant material may additionally comprise any of a protein, a growth factor, an antibiotic, a drug or any other therapeutic agent alone or in combination required to be released in a controlled manner at the surgical site.
  • the insoluble anhydrite may have been formed by heating soluble anhydrite, and desirably at a temperature of greater than 650°C.
  • the insoluble anhydrite may have been formed by hydrothermal treatment of gypsum, and desirably at temperatures greater than 300°C.
  • the soluble anhydrite may be insolubilised by surface coating with a calcium phosphate material.
  • the implant material may comprise a composite of a bioresorbable polymer and a filler, wherein the filler comprises soluble or insoluble anhydrite.
  • the filler material may include alpha tri-calcium phosphate.
  • the polymer component is preferably synthetic, and may comprise a polyester.
  • the polymer component preferably comprises one or more polymers or co-polymers of lactic acid (L and/or DL), glycolic acid, hydroxybutyric acid, hydroxy valeric acid, poly dioxanone, poly caprolactone, poly ethylene oxide or poly butylene terephthalate.
  • L and/or DL lactic acid
  • glycolic acid hydroxybutyric acid
  • hydroxy valeric acid poly dioxanone
  • poly caprolactone poly ethylene oxide or poly butylene terephthalate.
  • the filler preferably has a particle size of substantially less than 100 microns.
  • the filler preferably constitutes between 1 % and 50% of the material by weight, and desirably between 20% and 40%.
  • the material may be a bone graft or bone void filler material in the form of powder, pellets, granules or morsels.
  • the invention still further provides a component made of a material according to any of the preceding fifteen paragraphs.
  • the component may comprise any of a screw, pin, plate, tack, suture, wound care patch, spinal spacer, osteotomy wedge, non-woven scaffold for tissue engineering applications or other item usable in surgery and related fields of medicine.
  • Table 1 a relationship between the calcination temperature of gypsum and the pH of the resultant powder when suspended in water.
  • the pH increases as the calcination temperature increases, and becomes alkaline when the calcination temperature exceeds approximately 650°C and the alkalinity increases as the calcination temperature increases.
  • the insoluble anhydrite which has been calcined at temperatures of 650°C or above has the potential for pH buffering of the acidic degradation products of the polymer while being amenable to dissolution mediated resorption in a time frame which can be more closely matched to the rate of degradation of the polymer and the rate of healing and new bone formation.
  • Alpha tri-calcium phosphate ( ⁇ TCP) is the high temperature phase of TCP and is formed by calcining beta TCP to temperatures in excess of about 1200°C. It is thermodynamically unstable at room temperature and in the presence of water rapidly converts to a calcium deficient hydroxyapatite according to the following equation:-
  • This material is more soluble than HA or beta TCP. It is osteoconductive and is bio- absorbed through both dissolution and cell mediated processes.
  • Alpha TCP when present as a filler in a bio-absorbable polymer would confer similar advantages to HA or beta TCP but in addition would have the potential to be re-modelled into new bone more rapidly.
  • biodegradable implant materials according to the invention will now be described.
  • Gypsum powder having a particle size substantially less than 250 microns was heated to 400°C and held for 2 hours at that temperature before cooling to give soluble anhydrite.
  • This powder was insolubilised by soaking in a 0.1 molar sodium orthophosphate solution for a time to give an insoluble surface coating on the powder of calcium orthophosphate. The temperature and time of soaking and concentration of the soluble orthophosphate salt can be adjusted to vary the thickness of the surface coating.
  • This powder was then pressed into pellets using a tablet press to give a material suitable for bony site implantation applications.
  • An insoluble anhydrite powder according to example 1 or an insolubilised soluble anhydrite powder according to example 2 was prepared with a particle size substantially less than 100 microns to be used as a filler in a bioresorbable polymer.
  • Gypsum powder of particle size substantially less than 150 microns was calcined at a temperature of 900°C for 2 hours to form the insoluble anhydrite. This was crushed to give a powder of less than 75 microns which was added to poly L-lactide of molecular weight 200,000 Daltons in the proportions PLLA:CS, 4:1 by weight. The compounded mixture was injection moulded to give bony site implant devices.
  • a mixture of gypsum powder which had been calcined to 1200°C and alpha TCP in the ratio 1:2 parts by weight were crushed to pass a 100 micron aperture sieve and blended into a poly (L-lactide-co-DL-lactide) lactide of molecular weight 300,000 Daltons and L : DL ratio of 70 : 30 molar.
  • the percentage fill was 35% by weight.
  • the mixture was formed into implantable bony site fixation devices including plates, pins and screws by the techniques of compression moulding, extrusion and injection moulding respectively.
  • Gypsum powder having a particle size of substantially less than 250 microns was heated to a temperature of 800°C and held at temperature for one hour prior to cooling.
  • the insoluble anhydrite so formed was mixed together with bone morphogenic protein in the proportions of anhydrite: protein, 99.95:0.05 by weight.
  • the mixture was pressed into pellets which were subsequently used in a bone grafting procedure to provide a graft material having an enhanced ability to promote new bone formation by the steady and controlled release of the therapeutic agent.
  • Gypsum powder having a particle size of substantially less than 250 microns was hydrthermally treated in an autoclave at 300°C for 1 hour.
  • the resulting insoluble anhydrite was dried and crushed to give a powder having a particle size substantially less than 100 microns. This powder was used as a material component of a porous bioabsorbable scaffold for cell culture for a tissue engineering application.
  • the material may constitute a filler in a bioabsorbable polymer which degrades in a similar time frame to the polymer. As the material degrades it provides a slowly soluble source of calcium and sulphate ions.
  • the particle size of the filler is important. Smaller particles are better from the point of view of improved mechanical properties.
  • the preferred particle size for the filler component is substantially less than 100 microns.
  • the filler may comprise an insoluble anhydrite, an insolubilised soluble anhydrite, or a mixture of these components.
  • the filler may also include other materials such as hydroxyapatite or tri-calcium phosphate.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Materials Engineering (AREA)
  • Surgery (AREA)
  • Engineering & Computer Science (AREA)
  • Inorganic Chemistry (AREA)
  • Composite Materials (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Dermatology (AREA)
  • Medicinal Chemistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Materials For Medical Uses (AREA)

Abstract

L'invention a trait à un matériau d'implant biodégradable comprenant du sulfate de calcium anhydre sous forme d'anhydrite soluble ou insoluble. Ledit matériau peut être utilisé tout seul ou en combinaison avec un polymère ou un agent thérapeutique biorésorbable.
PCT/GB2002/005860 2002-01-03 2002-12-20 Materiaux d'implant biodegradables WO2003059409A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2002366969A AU2002366969A1 (en) 2002-01-03 2002-12-20 Biodegradable implant materials

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB0200051.1A GB0200051D0 (en) 2002-01-03 2002-01-03 Biodegradable implant materials
GB0200051.1 2002-01-03

Publications (2)

Publication Number Publication Date
WO2003059409A2 true WO2003059409A2 (fr) 2003-07-24
WO2003059409A3 WO2003059409A3 (fr) 2003-11-27

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PCT/GB2002/005860 WO2003059409A2 (fr) 2002-01-03 2002-12-20 Materiaux d'implant biodegradables

Country Status (3)

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AU (1) AU2002366969A1 (fr)
GB (1) GB0200051D0 (fr)
WO (1) WO2003059409A2 (fr)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1642601A2 (fr) 2004-09-27 2006-04-05 Ethicon, Inc. Combinaison d'un ancrage de suture et d'un matériau de comblement osseux
WO2008095874A1 (fr) 2007-02-07 2008-08-14 Materia Nova Compositions à base de polylactide
CN101138657B (zh) * 2006-09-04 2010-05-12 叶南辉 富含凝血生长因子的生物医学填充材的制造方法
US8124118B2 (en) 2003-10-22 2012-02-28 Lidds Ab Composition comprising biodegradable hydrating ceramics for controlled drug delivery
WO2014020259A1 (fr) * 2012-08-02 2014-02-06 Teknimed Dispositif resorbable et radio-opaque pour la fixation osseuse
WO2018002335A1 (fr) 2016-06-30 2018-01-04 Teknimed Susbtitut osseux et systeme d'injection autonome

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114699567B (zh) * 2022-04-15 2023-01-10 开封市卫生学校 一种可促进内皮细胞粘附和分化的体内植入物

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3445738A1 (de) * 1984-12-14 1986-06-19 Draenert Klaus Implantat zur knochenverstaerkung und verankerung von knochenschrauben, implantaten oder implantatteilen
US5681873A (en) * 1993-10-14 1997-10-28 Atrix Laboratories, Inc. Biodegradable polymeric composition
GB9407135D0 (en) * 1994-04-11 1994-06-01 Aberdeen University And Plasma Treatment of osteoporosis
AU3795395A (en) * 1994-11-30 1996-06-06 Ethicon Inc. Hard tissue bone cements and substitutes
GB9820874D0 (en) * 1998-09-26 1998-11-18 Smith & Nephew Melt-mouldable composites
US6165486A (en) * 1998-11-19 2000-12-26 Carnegie Mellon University Biocompatible compositions and methods of using same
GB9916601D0 (en) * 1999-07-16 1999-09-15 Biocomposites Ltd Calcium sulphate
EP1229858B1 (fr) * 1999-11-01 2007-05-23 Osteobiologics, Inc. Materiau d'implant biodegradable en polymere/ceramique presentant un profil de degradation bimodal

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8124118B2 (en) 2003-10-22 2012-02-28 Lidds Ab Composition comprising biodegradable hydrating ceramics for controlled drug delivery
US9034359B2 (en) 2003-10-22 2015-05-19 Lidds Ab Composition comprising biodegradable hydrating ceramics for controlled drug delivery
EP1642601A2 (fr) 2004-09-27 2006-04-05 Ethicon, Inc. Combinaison d'un ancrage de suture et d'un matériau de comblement osseux
EP1642601B1 (fr) * 2004-09-27 2014-07-09 Ethicon, Inc. Combinaison d'un ancrage de suture et d'un matériau de comblement osseux
CN101138657B (zh) * 2006-09-04 2010-05-12 叶南辉 富含凝血生长因子的生物医学填充材的制造方法
WO2008095874A1 (fr) 2007-02-07 2008-08-14 Materia Nova Compositions à base de polylactide
US8119713B2 (en) 2007-02-07 2012-02-21 Materia Nova Polylactide-based compositions
WO2014020259A1 (fr) * 2012-08-02 2014-02-06 Teknimed Dispositif resorbable et radio-opaque pour la fixation osseuse
FR2994097A1 (fr) * 2012-08-02 2014-02-07 Teknimed Dispositif resorbable et radio-opaque pour la fixation osseuse
US8911440B2 (en) 2012-08-02 2014-12-16 Teknimed Resorbable and radiopaque device for bone fixation
CN104507511A (zh) * 2012-08-02 2015-04-08 泰克尼迈德公司 用于骨固定的可再吸收且不透辐射的装置
WO2018002335A1 (fr) 2016-06-30 2018-01-04 Teknimed Susbtitut osseux et systeme d'injection autonome

Also Published As

Publication number Publication date
AU2002366969A1 (en) 2003-07-30
AU2002366969A8 (en) 2003-07-30
WO2003059409A3 (fr) 2003-11-27
GB0200051D0 (en) 2002-02-20

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