WO1989003695A1 - Ciment osseux - Google Patents

Ciment osseux Download PDF

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Publication number
WO1989003695A1
WO1989003695A1 PCT/DK1988/000170 DK8800170W WO8903695A1 WO 1989003695 A1 WO1989003695 A1 WO 1989003695A1 DK 8800170 W DK8800170 W DK 8800170W WO 8903695 A1 WO8903695 A1 WO 8903695A1
Authority
WO
WIPO (PCT)
Prior art keywords
bone
cement
reaction resin
growth stimulant
cell growth
Prior art date
Application number
PCT/DK1988/000170
Other languages
English (en)
Inventor
Sandra Downes
Original Assignee
Novo-Nordisk A/S
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 Novo-Nordisk A/S filed Critical Novo-Nordisk A/S
Publication of WO1989003695A1 publication Critical patent/WO1989003695A1/fr
Priority to NO90901765A priority Critical patent/NO901765L/no
Priority to DK098290A priority patent/DK98290A/da
Priority to FI902042A priority patent/FI902042A0/fi

Links

Classifications

    • 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
    • A61B17/58—Surgical instruments or methods for treatment of bones or joints; Devices specially adapted therefor for osteosynthesis, e.g. bone plates, screws, setting implements or the like
    • A61B17/88—Osteosynthesis instruments; Methods or means for implanting or extracting internal or external fixation devices
    • A61B17/8802—Equipment for handling bone cement or other fluid fillers
    • 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
    • A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
    • A61L24/001—Use of materials characterised by their function or physical properties
    • A61L24/0015—Medicaments; Biocides
    • 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
    • A61F2002/2817—Bone stimulation by chemical reactions or by osteogenic or biological products for enhancing ossification, e.g. by bone morphogenetic or morphogenic proteins [BMP] or by transforming growth factors [TGF]
    • 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
    • A61F2/46—Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor
    • A61F2002/4631—Special tools or methods for implanting or extracting artificial joints, accessories, bone grafts or substitutes, or particular adaptations therefor the prosthesis being specially adapted for being cemented
    • 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
    • A61L2300/22—Lipids, fatty acids, e.g. prostaglandins, oils, fats, waxes
    • A61L2300/222—Steroids, e.g. corticosteroids
    • 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
    • A61L2300/428—Vitamins, e.g. tocopherol, riboflavin
    • 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
    • A61L2300/43—Hormones, e.g. dexamethasone
    • 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 a bone cement which is useful for healing bone f actures, repairing bone defects and stablisation of prosthetic implants.
  • the cement may be mixed with antibiotics, such as Gen- tamicin, in order to avoid infections.
  • antibiotics such as Gen- tamicin
  • BMP bone or- phogenetic protein
  • the present invention is based on the discovery that growth hormone stimulates proliferation of bone cells by increasing the level of IGFl in the "target" cells, and that this effect causes the bone cells to multiply, grow, produce matrix and penetrate into the cement phase.
  • a bone cement comprising a combination of physiologi ⁇ cally acceptable reaction resin and a cell growth stimu ⁇ lant, preferably selected from the group consisting of somatotropins, somatomedines, parathyroid hormone (PTH), vitamin D and sex steroids.
  • Useful cell growth stimulants may be selected from the following groups:
  • Insulin-line growth factor 1 Insulin-line growth factor 1
  • the preferred cell growth stimulant to be used in the invention is human growth hormone (hGH). It has been shown that hGH, when it is incorporated in the cement, will increase the rate of healing of a bone fracture considerably and give a joint of increased strength.
  • hGH human growth hormone
  • reaction resin is used in the present concept to designate any casting resin in fluid, semi-liquid dough-like or ouldable form, capable of being cured or hardened at the temperature of application, usually between 30°C and 45°C, to form a strong, hard or flexible solid.
  • a preferred reaction resin is a polymerizing resin, such as a mixture of monomeric methyl methacrylate and pow ⁇ dered polymethyl methacrylate.
  • This composition also contains a catalyst and an accelerator.
  • examples of other useful resins are unsaturated polyesters or other liquid or mouldable polymerizing unsaturated compounds. Still other examples are ceramics and biodegradable organic galss.
  • a polycondensation resin can be used, such as a liquid high viscosity epoxy resin or a mixture of a di- or tri-isocyanate and a di- or trioi, producing a- polyurethane resin.
  • a polycondensation resin such as a liquid high viscosity epoxy resin or a mixture of a di- or tri-isocyanate and a di- or trioi, producing a- polyurethane resin.
  • Some polyurethane formulations will give a foamed resin, having increased flexibility and a high loading capacity for growth hormone or a similar cell grow ⁇ th stimulant.
  • the reaction resin In order to reduce the shrinking of the reaction resin during the curing process it can be mixed with a filler, such as Plaster of Paris or inorganic pigments or fibres. Also other additives, conventionally used in the plas ⁇ tics field, may be added.
  • a filler such as Plaster of Paris or inorganic pigments or fibres.
  • other additives conventionally used in the plas ⁇ tics field, may be added.
  • the reaction resin may be a monomeric cyano acrylate. This material will polymerize very fast at a hydrophiiic surface to a solid having a high bonding strength.
  • hGH hGH
  • a similar cell growth stimulant Used in total hip replacement surgery, the incorporation of hGH or a similar cell growth stimulant will result in increased bone remodelling and bone formation at the cement surface, leading to increased strength at the bone-cement interface. There is reduced risk of aseptic loosening and improved life time of the prosthesis.
  • the cement of the invention can be used in knee, elbow and schoulder replacement surgery or in small joint re- placement, such as fingers, wrists or toes.
  • the hGH can be applied to the bone-cement interface using supplying means, such as drainage tubes.
  • supplying means such as drainage tubes.
  • a bone fracture can be treated in the usual way using a plastic foam.
  • a drainage tube could be inserted and after operation a solution of hGH could be introduced to the cement through the drainage tube at a controlled rate.
  • the cement loaded with hGH can also be used to fill and repair bone defects and osteotomies.
  • the release of hGH from the material can lead to new bone cell formation in these areas.
  • This application may require the use of a biodegradable _polymer loaded with hGH-growth factors.
  • the release of hGH will cause increased bone cell forma ⁇ tion, the biodegradable polymer will eventually be resorbed and the defect will be filled with new bone.
  • hGH-loaded resin such as PMMA
  • PMMA can be used to repair bone fractures, give joint increased strength and cause increased bone remodelling in conjunction with devices such a a plate, screw or intermedullary pin.
  • a material was made from the following substances:
  • the sterile human growth hormone in powder form was added to the powder polymer component of PMMA bone cement and mixed thoroughly.
  • the liquid monomer component was then added to the mixture and mixed using a plastics spatula until a "dough-like" consistency was formed.
  • the material was then inserted into a pre- viously prepared bone cavity.
  • the growth hormone loaded cement was implanted into one femur of adult sandy lop rabbits, with plain cement in the contralateral femur as a control.
  • the rabbits were sacrificed and the bone-cement interface examined using transmission electronmicroscop .
  • the zirconium dioxide radiopague agent
  • the cement appeared clear (Fig. 1).
  • some invasion of the cement surface could be seen and new mineral deposited in the cement (Fig. 1).
  • a medial parapatellar incision was made and access to the knee patella was dislocated laterally to expose the intercondylar area.
  • the femoral medullary cavity was reamed to depth of 2 cm.
  • Approximately 0.5 ml of cement was injected into each knee.
  • On one side the cement was loaded with growth hor ⁇ mone (see above); plain cement was injected into the • contralaterial femur to act as a control. Further con- trols were used where both femura received plain PMMA cement.
  • the patellae were reduced and wounds closed with sutures. Post-operatively rabbits were kept unrestrained in sized cagoes (40 x 40 x 01).
  • the rabbits were divided into three groups which were sacrificed using an overdose of Euthatal (100 mg in 5 ml) after 1 month, 2 mohths and 4 months, respectively.
  • the femora were removed and processed for histology.
  • the sections were prepared to include undecalcified bone and intact bone cement making it possible to examine the bone-cement interface intact. Examination of the histology sections revealed that viable bone was growing in direct contact with the PMMA bone cement. When con ⁇ sidering PMMA as a drug delivery system it is important to establish whether the "target" tissue was in contact with the cement, this was clearly the case.
  • the bone-cement interface was found to be composed of between 14-21% mineralised bone, 28-52% osteoid bone and 41-60% cells.
  • the knee containing growth hormone loaded PMMA contained a higher percentage of osteoid at the bone-cement interface than in the knee containing plain bone cement. This was statistically significant (P ⁇ 0.01).
  • Remodelling of the bone occurs over a period of 4 months after surgery.
  • the _in vivo results of the rabbits experiments may be important to the problem of aseptic loosening.
  • the pre ⁇ cise mechanism of early loosening is not fully under ⁇ stood, but it has been postulated that the primary cause is the shrinkage of cement in the bone cavity and acco p- anying bone necrosis. Under such circumstances, it would initiate a rapid synthetic response following prosthetic replacement. This was clearly seen in the growth hormone loaded cement series when analysed after one month.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Surgery (AREA)
  • Public Health (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Cardiology (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Transplantation (AREA)
  • Vascular Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Materials Engineering (AREA)
  • Epidemiology (AREA)
  • Materials For Medical Uses (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Le ciment osseux décrit qui comprend une résine de réaction physiologiquement acceptable, telle qu'un mélange résineux de coulée à base de polyméthylméthacrylate (PMMA), est un stimulant de la croissance cellulaire tel qu'une hormone de croissance humaine, sert à soigner les fractures des os et à réparer les défauts osseux. Un tel ciment a une action promouvant la formation des cellules osseuses et confère aux articulations une résistance accrue.
PCT/DK1988/000170 1987-10-23 1988-10-24 Ciment osseux WO1989003695A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
NO90901765A NO901765L (no) 1987-10-23 1990-04-20 Bensement med cellevekststimulerende middel.
DK098290A DK98290A (da) 1987-10-23 1990-04-20 Bencement med indhold af vaekststimulerende midler
FI902042A FI902042A0 (fi) 1987-10-23 1990-04-23 Bencement som innehaoller celltillvaextstimulans.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB878724897A GB8724897D0 (en) 1987-10-23 1987-10-23 Material
GB8724897 1987-10-23

Publications (1)

Publication Number Publication Date
WO1989003695A1 true WO1989003695A1 (fr) 1989-05-05

Family

ID=10625798

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DK1988/000170 WO1989003695A1 (fr) 1987-10-23 1988-10-24 Ciment osseux

Country Status (6)

Country Link
EP (1) EP0386056A1 (fr)
JP (1) JPH03505406A (fr)
AU (1) AU629799B2 (fr)
FI (1) FI902042A0 (fr)
GB (1) GB8724897D0 (fr)
WO (1) WO1989003695A1 (fr)

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991011196A1 (fr) * 1990-02-02 1991-08-08 Novo Nordisk A/S Procede de traitement pour mammiferes utilisant un compose biologiquement actif
WO1991011195A1 (fr) * 1990-02-02 1991-08-08 Novo Nordisk A/S Procede de traitement pour mammiferes utilisant un compose biologiquement actif
WO1991011148A1 (fr) * 1990-02-02 1991-08-08 Troels Torp Andreassen Procede et dispositif d'administration locale de substances biologiquement actives
WO1993009819A1 (fr) * 1991-11-18 1993-05-27 Michael Braden Utilisation de biomateriaux dans la reparation tissulaire
WO1998019699A1 (fr) * 1996-11-05 1998-05-14 Novo Nordisk A/S Utilisation d'une hormone de croissance ou d'un secretagogue d'hormone de croissance pour stimuler la formation osseuse
WO2001070256A1 (fr) * 2000-03-24 2001-09-27 Lg Chem Investment, Ltd. Composition de somatotrophine se pretant mieux a l'injection par seringue
US6448315B1 (en) 1999-02-17 2002-09-10 Bone Support Ab Method for the preparation of UHMWPE doped with an antioxidant and an implant made thereof
EP1444263A2 (fr) * 2001-11-05 2004-08-11 Eli Lilly And Company Procede servant a ameliorer la stabilite d'un implant de liaison osseuse
WO2004071547A1 (fr) * 2003-02-12 2004-08-26 Ethicon Gmbh Materiau de remplissage osseux renfermant un steroide anabolisant
EP1767213A2 (fr) * 2001-11-05 2007-03-28 Eli Lilly & Company Procédé servant à ameliorer la stabilité d'un implant de liaison osseuse
US7417077B2 (en) 2000-07-17 2008-08-26 Bone Support Ab Composition for an injectable bone mineral substitute material
CN101663043A (zh) * 2007-04-27 2010-03-03 尤尼基因实验室公司 促进和保持骨生长的方法和组合物
US7935121B2 (en) 2003-11-11 2011-05-03 Bone Support Ab Device for providing spongy bone with bone substitute and/or bone reinforcing material, bone substitute and/or bone reinforcing material and method
US7938572B2 (en) 2004-06-22 2011-05-10 Bone Support Ab Device for producing a hardenable mass
US7972630B2 (en) * 2000-04-11 2011-07-05 Bone Support Ab Injectable bone mineral substitute material
US20150150616A1 (en) * 2009-11-20 2015-06-04 Zimmer Knee Creations, Inc. Subchondral treatment of joint pain
US9180137B2 (en) 2010-02-09 2015-11-10 Bone Support Ab Preparation of bone cement compositions
US9730744B2 (en) 2009-11-20 2017-08-15 Zimmer Knee Creations, Inc. Method for treating joint pain and associated instruments
US10294107B2 (en) 2013-02-20 2019-05-21 Bone Support Ab Setting of hardenable bone substitute

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH695985A5 (de) * 2002-01-21 2006-11-15 Straumann Holding Ag Oberflächenmodifizierte Implantate.

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4526909A (en) * 1984-01-09 1985-07-02 Regents Of The University Of California Polymethylmethacrylate delivery system for bone morphogenetic protein
EP0198213A2 (fr) * 1985-03-15 1986-10-22 Yeda Research And Development Company, Ltd. Procédé et compositions contenant un dérivé de la vitamine D pour le traitement local de fractures osseuses
US4620327A (en) * 1984-07-05 1986-11-04 Caplan Arnold I Process of adapting soluble bone protein for use in stimulating osteoinduction

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE8405155D0 (sv) * 1984-10-16 1984-10-16 Bengt Mjoberg Bencement

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4526909A (en) * 1984-01-09 1985-07-02 Regents Of The University Of California Polymethylmethacrylate delivery system for bone morphogenetic protein
US4620327A (en) * 1984-07-05 1986-11-04 Caplan Arnold I Process of adapting soluble bone protein for use in stimulating osteoinduction
EP0198213A2 (fr) * 1985-03-15 1986-10-22 Yeda Research And Development Company, Ltd. Procédé et compositions contenant un dérivé de la vitamine D pour le traitement local de fractures osseuses

Cited By (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991011195A1 (fr) * 1990-02-02 1991-08-08 Novo Nordisk A/S Procede de traitement pour mammiferes utilisant un compose biologiquement actif
WO1991011148A1 (fr) * 1990-02-02 1991-08-08 Troels Torp Andreassen Procede et dispositif d'administration locale de substances biologiquement actives
WO1991011196A1 (fr) * 1990-02-02 1991-08-08 Novo Nordisk A/S Procede de traitement pour mammiferes utilisant un compose biologiquement actif
WO1993009819A1 (fr) * 1991-11-18 1993-05-27 Michael Braden Utilisation de biomateriaux dans la reparation tissulaire
US5468787A (en) * 1991-11-18 1995-11-21 Braden; Michael Biomaterials for tissue repair
WO1998019699A1 (fr) * 1996-11-05 1998-05-14 Novo Nordisk A/S Utilisation d'une hormone de croissance ou d'un secretagogue d'hormone de croissance pour stimuler la formation osseuse
US6448315B1 (en) 1999-02-17 2002-09-10 Bone Support Ab Method for the preparation of UHMWPE doped with an antioxidant and an implant made thereof
WO2001070256A1 (fr) * 2000-03-24 2001-09-27 Lg Chem Investment, Ltd. Composition de somatotrophine se pretant mieux a l'injection par seringue
US7972630B2 (en) * 2000-04-11 2011-07-05 Bone Support Ab Injectable bone mineral substitute material
US7417077B2 (en) 2000-07-17 2008-08-26 Bone Support Ab Composition for an injectable bone mineral substitute material
EP1444263A2 (fr) * 2001-11-05 2004-08-11 Eli Lilly And Company Procede servant a ameliorer la stabilite d'un implant de liaison osseuse
EP1767213A2 (fr) * 2001-11-05 2007-03-28 Eli Lilly & Company Procédé servant à ameliorer la stabilité d'un implant de liaison osseuse
EP1767213A3 (fr) * 2001-11-05 2007-04-25 Eli Lilly & Company Procédé servant à ameliorer la stabilité d'un implant de liaison osseuse
EP1444263A4 (fr) * 2001-11-05 2005-04-20 Lilly Co Eli Procede servant a ameliorer la stabilite d'un implant de liaison osseuse
WO2004071547A1 (fr) * 2003-02-12 2004-08-26 Ethicon Gmbh Materiau de remplissage osseux renfermant un steroide anabolisant
US7935121B2 (en) 2003-11-11 2011-05-03 Bone Support Ab Device for providing spongy bone with bone substitute and/or bone reinforcing material, bone substitute and/or bone reinforcing material and method
US7938572B2 (en) 2004-06-22 2011-05-10 Bone Support Ab Device for producing a hardenable mass
US8297831B2 (en) 2004-06-22 2012-10-30 Bone Support Ab Device for producing a hardenable mass
CN101663043A (zh) * 2007-04-27 2010-03-03 尤尼基因实验室公司 促进和保持骨生长的方法和组合物
CN101663043B (zh) * 2007-04-27 2014-03-12 尤尼基因实验室公司 促进和保持骨生长的方法和组合物
US20150150616A1 (en) * 2009-11-20 2015-06-04 Zimmer Knee Creations, Inc. Subchondral treatment of joint pain
US9717544B2 (en) * 2009-11-20 2017-08-01 Zimmer Knee Creations, Inc. Subchondral treatment of joint pain
US9730744B2 (en) 2009-11-20 2017-08-15 Zimmer Knee Creations, Inc. Method for treating joint pain and associated instruments
US10271883B2 (en) 2009-11-20 2019-04-30 Zimmer Knee Creations, Inc. Method for treating joint pain and associated instruments
US11006992B2 (en) 2009-11-20 2021-05-18 Zimmer Knee Creations, Inc. Method for treating joint pain and associated instruments
US9180137B2 (en) 2010-02-09 2015-11-10 Bone Support Ab Preparation of bone cement compositions
US10294107B2 (en) 2013-02-20 2019-05-21 Bone Support Ab Setting of hardenable bone substitute
US10994998B2 (en) 2013-02-20 2021-05-04 Bone Support Ab Setting of hardenable bone substitute

Also Published As

Publication number Publication date
EP0386056A1 (fr) 1990-09-12
AU2616088A (en) 1989-05-23
AU629799B2 (en) 1992-10-15
FI902042A0 (fi) 1990-04-23
GB8724897D0 (en) 1987-11-25
JPH03505406A (ja) 1991-11-28

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