WO1993001841A1 - Ameliorations de billes acryliques renfermant des antibiotiques - Google Patents
Ameliorations de billes acryliques renfermant des antibiotiques Download PDFInfo
- Publication number
- WO1993001841A1 WO1993001841A1 PCT/EP1992/001619 EP9201619W WO9301841A1 WO 1993001841 A1 WO1993001841 A1 WO 1993001841A1 EP 9201619 W EP9201619 W EP 9201619W WO 9301841 A1 WO9301841 A1 WO 9301841A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- antibiotic
- polymerisation
- bone
- synthetic resin
- therapeutic agent
- Prior art date
Links
- 230000003115 biocidal effect Effects 0.000 title claims abstract description 26
- 239000011324 bead Substances 0.000 title claims abstract description 25
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 title 1
- 210000000988 bone and bone Anatomy 0.000 claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 10
- 239000003242 anti bacterial agent Substances 0.000 claims abstract description 8
- 229940124597 therapeutic agent Drugs 0.000 claims abstract description 8
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 4
- 238000001816 cooling Methods 0.000 claims abstract description 4
- 229910052751 metal Inorganic materials 0.000 claims description 9
- 239000002184 metal Substances 0.000 claims description 9
- 239000008187 granular material Substances 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 6
- 239000003054 catalyst Substances 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 4
- 230000000844 anti-bacterial effect Effects 0.000 claims description 3
- 238000002513 implantation Methods 0.000 claims description 3
- 238000009826 distribution Methods 0.000 claims description 2
- 238000010348 incorporation Methods 0.000 claims description 2
- 239000000178 monomer Substances 0.000 claims description 2
- 229920003002 synthetic resin Polymers 0.000 claims 5
- 239000000057 synthetic resin Substances 0.000 claims 5
- 229920005989 resin Polymers 0.000 claims 3
- 239000011347 resin Substances 0.000 claims 3
- 230000001771 impaired effect Effects 0.000 claims 1
- 230000001394 metastastic effect Effects 0.000 claims 1
- 206010061289 metastatic neoplasm Diseases 0.000 claims 1
- 239000002245 particle Substances 0.000 claims 1
- 239000000814 tuberculostatic agent Substances 0.000 claims 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 abstract description 18
- 239000004926 polymethyl methacrylate Substances 0.000 abstract description 18
- 229940088710 antibiotic agent Drugs 0.000 abstract description 7
- 239000002639 bone cement Substances 0.000 abstract description 6
- 239000003795 chemical substances by application Substances 0.000 abstract description 5
- 238000006116 polymerization reaction Methods 0.000 abstract description 5
- 238000001356 surgical procedure Methods 0.000 abstract description 5
- 206010031252 Osteomyelitis Diseases 0.000 abstract description 3
- 230000002365 anti-tubercular Effects 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract description 2
- 230000000069 prophylactic effect Effects 0.000 abstract description 2
- 239000002246 antineoplastic agent Substances 0.000 abstract 1
- 229940127089 cytotoxic agent Drugs 0.000 abstract 1
- 230000003685 thermal hair damage Effects 0.000 abstract 1
- 239000004568 cement Substances 0.000 description 16
- 208000015181 infectious disease Diseases 0.000 description 8
- 239000000203 mixture Substances 0.000 description 7
- 238000009792 diffusion process Methods 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 239000000654 additive Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000002980 postoperative effect Effects 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 239000004925 Acrylic resin Substances 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- MCMNRKCIXSYSNV-UHFFFAOYSA-N ZrO2 Inorganic materials O=[Zr]=O MCMNRKCIXSYSNV-UHFFFAOYSA-N 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000004873 anchoring Methods 0.000 description 1
- 230000008081 blood perfusion Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 238000012829 orthopaedic surgery Methods 0.000 description 1
- RVTZCBVAJQQJTK-UHFFFAOYSA-N oxygen(2-);zirconium(4+) Chemical compound [O-2].[O-2].[Zr+4] RVTZCBVAJQQJTK-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000005096 rolling process Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
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
- 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
- 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
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
- A61L24/04—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials
- A61L24/06—Surgical adhesives or cements; Adhesives for colostomy devices containing macromolecular materials obtained by reactions only involving carbon-to-carbon unsaturated bonds
-
- 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
-
- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J2237/00—Discharge tubes exposing object to beam, e.g. for analysis treatment, etching, imaging
- H01J2237/30—Electron or ion beam tubes for processing objects
- H01J2237/317—Processing objects on a microscale
- H01J2237/31701—Ion implantation
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Definitions
- This invention relates to orthopaedics and to improvements in the design of polymethyl methacrylate (PMMA) beads containing admixed antibiotic or other therapeutic agents.
- PMMA polymethyl methacrylate
- Antibiotic-containing PMMA beads are intended for implantation within the body at the time of operation during orthopaedic surgical procedures in order to provide prophylactic post-operative antibiotic cover, or may be used in the treatment of deep infections involving bone.
- Deep infection following bone or joint surgery is a known complication of such procedures with an incidence of about 1.5 percent.
- joint replacement surgery it is the cause of a small but significant proportion of failures, usually requiring the removal of the prosthetic components to allow effective treatment of the infected bone.
- osteomyelitis may be caused by staphyloccocal infection, perhaps by haematogenous spead from some superficial infected site or following trauma, by salmonella, tuberculosis or other organisms. These are serious conditions requiring careful management.
- Antibiotics administered systemically are not very effective in the treatment because of the relatively sparse blood perfusion in bone and, consequently, the low concentration of antibiotic obtained at the site of the infection.
- the bone cement is an acrylic resin (polymethyl methacrylate, abbreviated PMMA) which is usually supplied for use in the operating theatre in a two component form, a powder, consisting of small granules of partially polymerised methacrylate, and a liquid, consisting mainly of monomeric methyl methacrylate but containing also a catalyst and other agents which serve to promote a further polymerisation reaction during "curing".
- PMMA polymethyl methacrylate
- the powder and liquid are mixed together in theatre immediately before the cement is required for use.
- the mixture assumes the consistency of a thick "dough" one or two minutes after mixing and is applied to the bone and/or prosthetic components in this condition. Within ten minutes or so the mixture has set into a hard, solid mass effectively anchoring the prosthetic component to the bone.
- Antibiotics in the form of dry powders, can be added to the bone cement at the time of mixing and become dispersed and embedded in the cured PMMA mass.
- the cement is slightly porous and permeable to water and water-soluble molecules so that the antibiotic slowly diffuses out from the solid cement and into the surrounding tissues, thus maintaining high bactericidal concentrations at and near the operation site.
- Some of the commercially-produced formulations of bone cement contain inorganic materials to render the cement more opaque to x-rays and thus to help visualise the shape and extent of the cement mantle on post-operative x-ray examination.
- Bariu m sulphate or zirconium dioxide are two compounds which are commonly used. It has been shown that the presence of these inorganic additives greatly increases the diffusion coefficient of water soluble molecules in the cement. Almost all antibiotic therapy with PMMA-dispensed agents is based on the use of radio-opaque bone cement formulations, since the rate of drug delivery from PMMA with no inorganic additive is usually too low.
- antibiotic-containing PMMA beads have become commercially available, usually in the form of "chains" threaded on a flexible stainless steel wire. These ' are used in the treatment of bone infections and can be packed into the space resulting from surgical removal of infected or damaged bone or within the medullary cavity of long bones. These chained beads may be removed after the infection has been brought under control thus minimising needless and undesirable exposure to continuing dosage of antibiotic which carries the risk of the development of antibiotic-resistant organisms.
- the PMMA is used solely as a vehicle for the antibiotic and, since it is not required to provide a strong means of attachment for a prosthetic component, its mechanical properties are not important. High concentrations of antibiotic (which impair the mechanical properties of the cured cement) may therefore be used.
- Antibiotic -containing beads are most usually pre-manufactured and delivered to the theatre in sterile packs ready for use.
- the polymerisation reaction is exothermic, thus the temperature of the cement rises during the curing process.
- the maximum temperature attained will depend on the thickness of the cement mantle, the proximity of metallic prosthetic components and so on.
- the temperature at the centre of a ball of cement several centimetres in diameter will reach approximately 120 degrees Centigrade during the curing process and sections only two millimetres thick will exceed 80 degrees Centigrade.
- Many of the antibiotics which are suitable for use prophylactically or therapeuticaliy in the control of deep infections involving bone are unstable at these temperatures and are therefore rendered ineffective during the cement polymerisation reaction.
- the purpose of the present invention is to provide a method of manufacturing antibiotic-containing PMMA beads which avoids exposure o: the antibiotic to damaging temperatures.
- Bumps or other raised areas may be formed on one cr other of the metal sheets to control the separation between them during the rolling process. These operations must be completed before the polymerisation reaction has progressed more than a few percent but this does not present a difficulty.
- the rolled-down sandwich is then set aside to allow the cement to cure. Because of the thin section of cement, in contact on each side with the metal plates, the temperature rise during polymerisation is limited by the conduction of heat away from the polymer into the metal. In this way the maximum temperature which is attained may be limited to less than 10 Centigrade degrees above the ambient temperature. If a particularly heat-sensitive antibiotic is being used lower maximum temperatures may be obtained by providing means of cooling the plates, by working in a cooler environment or by using precooled materials, plates and rollers.
- the cement When curing is complete the cement is broken out from the containing plates and is then broken up by passing it through serrated rollers so as to produce granules. These are subsequently graded in size by means of sieves.
- the granule size has a considerable effect on the rate at which the antibiotic will be released, by diffusion, from the completed bead and in consequence the maximum size and the spectrum of sizes which are used in the later stages requires to be carefully controlled.
- the maximum dimensions of the granules will most often be in the range 0.5 to 1 .7 millimetres, although the invention is not restricted to this range of sizes.
- the bead further small quantities of the monomeric methyl methacrylate and catalyst are added to the granular mix and the bead formed by moulding or other appropriate process.
- a hole for the wire on which the beads will be strung is formed at this stage.
- the diameter of the completed beads will be, typically, between 10 and 20 millimetres.
- the granules are compacted and will become firmly bonded to each other at their points of contact as a result of further polymerisation which takes place at these points. Though this reaction is again exothermic and some temperature rise will take place the quantity of reacting material is small, dependent mainly on the amount of liquid monomer which is added, and the maximum temperature attained is therefore acceptable.
- the resulting bead has an open, porous structure with intergranuiar voids which are large compared to those found in conventionally prepared, cured PMMA.
- the mechanical strength is thus relatively low but this is of no consequence since the material is not required to be load-bearing.
- the porosity will considerably increase the rate of diffusion of the water soluble antibiotic molecules from the bead and into the surrounding tissues after implantation, which is advantageous.
- the diffusion rate can be adjusted to suit the pharmacological requirements by variation of the granule size (and size distribution) and. of course, by selection of the original antibiotic content.
- PMMA beads of the form described above may be used with advantage to provide long duration, continuing delivery of therapeutic agents other than antibiotics.
- anti-tuberculous drugs and compounds used in chemotherapy for tumour may be incorporated. Many such agents are heat sensitive and thus unsuitable for incorporation into PMMA beads of "solid" design.
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Surgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Materials Engineering (AREA)
- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
Abstract
Les implantations de petites billes de méthacrylate de polyméthyle renfermant des antibiotiques, comme ciment de prothèse osseuse, ont été utilisées pour assurer la couverture prophylactique à l'issue d'interventions chirurgicales orthopédiques ou de traitements d'infections osseuses. Le choix de l'antibiotique est restreint par la température de la réaction de polymérisation exothermique, altérant de nombreux agents antibiotiques qui seraient autrement très utiles. En réalisant la polymérisation en deux étapes et en prévoyant des moyens de refroidissement au cours de la première, la température maximale à laquelle l'agent thérapeutique est exposé se trouve considérablement abaissée, ce qui permet d'éviter ainsi son altération par la chaleur. Des considérations similaries s'appliquent également lorsque, par exemple, on met en ÷uvre des substances pharmaceutiques anti-tuberculeuses et des agents chimiothérapeutiques pour le traitement des tumeurs osseuses, substances qui pour la plupart sont sensibles à la chaleur. Elles peuvent être incorporées dans les billes de méthacrylate de polyméthyle ainsi modifiées.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9115901.2 | 1991-07-23 | ||
| GB919115901A GB9115901D0 (en) | 1991-07-23 | 1991-07-23 | Improvements in antibiotic-containing acrylic beads |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1993001841A1 true WO1993001841A1 (fr) | 1993-02-04 |
Family
ID=10698837
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP1992/001619 WO1993001841A1 (fr) | 1991-07-23 | 1992-07-16 | Ameliorations de billes acryliques renfermant des antibiotiques |
Country Status (2)
| Country | Link |
|---|---|
| GB (1) | GB9115901D0 (fr) |
| WO (1) | WO1993001841A1 (fr) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002009783A1 (fr) * | 2000-08-01 | 2002-02-07 | Coripharm Medizinprodukte Gmbh & Co. Kg | Systeme modulaire d'implant contenant des agents actifs et son procede de fabrication |
| US8921365B2 (en) | 2007-07-23 | 2014-12-30 | Biomet Deutschland Gmbh | Pharmaceutical composition, substrate comprising a pharmaceutical composition, and use of a pharmaceutical composition |
| US9155671B2 (en) | 2012-10-16 | 2015-10-13 | Surmodics, Inc. | Wound packing device and methods |
| US10029031B2 (en) * | 2015-10-28 | 2018-07-24 | Warsaw Orthopedic, Inc. | Bone void filler having sustained therapeutic agent release |
| US10201457B2 (en) | 2014-08-01 | 2019-02-12 | Surmodics, Inc. | Wound packing device with nanotextured surface |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0111759A2 (fr) * | 1982-12-11 | 1984-06-27 | Beiersdorf Aktiengesellschaft | Matériau chirurgical |
| US4554686A (en) * | 1984-02-29 | 1985-11-26 | Technical Research Associates, Inc. | Polymethylmethacrylate bone cements and methods for preparing such bone cements |
| WO1986002370A1 (fr) * | 1984-10-16 | 1986-04-24 | Ferring Laboratories, Inc. | Ciment osseux polymerisant a froid |
| DE3738422A1 (de) * | 1987-11-12 | 1989-05-24 | Beiersdorf Ag | Chirurgisches material |
| GB2219303A (en) * | 1988-06-01 | 1989-12-06 | Tecres Spa | Two phase acrylic cement mixture, particularly suitable for orthopaedics |
| EP0361408A2 (fr) * | 1988-09-26 | 1990-04-04 | Wolff & Kaaber A/S | Ciment osseux |
| FR2638972A1 (fr) * | 1988-11-14 | 1990-05-18 | Osteal Medical Laboratoires | Ciment pour la fixation de protheses osseuses |
-
1991
- 1991-07-23 GB GB919115901A patent/GB9115901D0/en active Pending
-
1992
- 1992-07-16 WO PCT/EP1992/001619 patent/WO1993001841A1/fr active Application Filing
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0111759A2 (fr) * | 1982-12-11 | 1984-06-27 | Beiersdorf Aktiengesellschaft | Matériau chirurgical |
| US4554686A (en) * | 1984-02-29 | 1985-11-26 | Technical Research Associates, Inc. | Polymethylmethacrylate bone cements and methods for preparing such bone cements |
| WO1986002370A1 (fr) * | 1984-10-16 | 1986-04-24 | Ferring Laboratories, Inc. | Ciment osseux polymerisant a froid |
| DE3738422A1 (de) * | 1987-11-12 | 1989-05-24 | Beiersdorf Ag | Chirurgisches material |
| GB2219303A (en) * | 1988-06-01 | 1989-12-06 | Tecres Spa | Two phase acrylic cement mixture, particularly suitable for orthopaedics |
| EP0361408A2 (fr) * | 1988-09-26 | 1990-04-04 | Wolff & Kaaber A/S | Ciment osseux |
| FR2638972A1 (fr) * | 1988-11-14 | 1990-05-18 | Osteal Medical Laboratoires | Ciment pour la fixation de protheses osseuses |
Non-Patent Citations (1)
| Title |
|---|
| JOURNAL OF BIOMEDICAL MATERIALS RESEARCH vol. 20, 1986, pages 839 - 852 G.M. BRAUER ET AL. 'DPENDENCE OF CURING TIME, PEAK TEMPERATURE, AND MECHANICAL PROPERTIES ON THE COMPOSITION OF BONE CEMENT' * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002009783A1 (fr) * | 2000-08-01 | 2002-02-07 | Coripharm Medizinprodukte Gmbh & Co. Kg | Systeme modulaire d'implant contenant des agents actifs et son procede de fabrication |
| US8003121B1 (en) | 2000-08-01 | 2011-08-23 | Aap Biomaterials Gmbh & Co. Kg | Modular implant system containing active substances and method for the production thereof |
| US8921365B2 (en) | 2007-07-23 | 2014-12-30 | Biomet Deutschland Gmbh | Pharmaceutical composition, substrate comprising a pharmaceutical composition, and use of a pharmaceutical composition |
| US9968710B2 (en) | 2007-07-23 | 2018-05-15 | Biomet Deutschland Gmbh | Pharmaceutical composition, substrate comprising a pharmaceutical composition, and use of a pharmaceutical composition |
| US9155671B2 (en) | 2012-10-16 | 2015-10-13 | Surmodics, Inc. | Wound packing device and methods |
| US10080688B2 (en) | 2012-10-16 | 2018-09-25 | Surmodics, Inc. | Wound packing device and method |
| US10201457B2 (en) | 2014-08-01 | 2019-02-12 | Surmodics, Inc. | Wound packing device with nanotextured surface |
| US10029031B2 (en) * | 2015-10-28 | 2018-07-24 | Warsaw Orthopedic, Inc. | Bone void filler having sustained therapeutic agent release |
Also Published As
| Publication number | Publication date |
|---|---|
| GB9115901D0 (en) | 1991-09-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US7138442B2 (en) | Reduced exothermic bone replacement cement | |
| CN1163275C (zh) | 在超临界流体中制得的生物功能聚合物 | |
| JP2700881B2 (ja) | 医薬デポ剤 | |
| US4230686A (en) | Drug excipient of silicone rubber | |
| US5807567A (en) | Calcium sulfate controlled release matrix | |
| AU736940B2 (en) | Hydrogel composites and superporous hydrogel composites having fast swelling, high mechanical strength, and superabsorbent properties | |
| US3507952A (en) | Sustained release bolus for animal husbandry | |
| US5266248A (en) | Method of producing hydroxylapatite base porous beads filler for an organism | |
| JP2003533468A (ja) | タンパク質マトリクス物質、製造並びにその製造及び使用 | |
| JPS61243015A (ja) | 細胞増殖抑止剤を含有するデポ医薬 | |
| WO1996011715A1 (fr) | Composition de reparation des tissus durs et son unite de distribution | |
| JP2009545332A (ja) | 骨セメント組成物、およびこれを作る方法 | |
| CN100502954C (zh) | 生物可吸收的复合材料 | |
| GB2091554A (en) | Rod-like Moulded Drug | |
| Otsuka et al. | Antibiotic delivery system using bioactive bone cement consisting of Bis-GMA/TEGDMA resin and bioactive glass ceramics | |
| JP2004236729A (ja) | 骨セメント組成物 | |
| WO1993001841A1 (fr) | Ameliorations de billes acryliques renfermant des antibiotiques | |
| JPS626522B2 (fr) | ||
| JPH02255139A (ja) | 成形手術用デバイス | |
| US4652443A (en) | Slow-release composite and process for producing the same | |
| EP0339035B1 (fr) | Enveloppes contenant de l'hydrogel | |
| CN108159021B (zh) | 一种载有促进骨形成蛋白及消除关节炎症状药物的双层复合缓释微球及其制备方法 | |
| JPH0244050A (ja) | 水硬性ペレット | |
| JPH0734817B2 (ja) | 医科用および歯科用硬化性材料および多孔性材料 | |
| CN116036384B (zh) | 自供氧抗菌填充固定材料的制备方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): JP US |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IT LU MC NL SE |
|
| 122 | Ep: pct application non-entry in european phase |