WO1999066966A1 - Thin-film coating for a bone implant - Google Patents
Thin-film coating for a bone implant Download PDFInfo
- Publication number
- WO1999066966A1 WO1999066966A1 PCT/EA1998/000002 EA9800002W WO9966966A1 WO 1999066966 A1 WO1999066966 A1 WO 1999066966A1 EA 9800002 W EA9800002 W EA 9800002W WO 9966966 A1 WO9966966 A1 WO 9966966A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- layer
- bioactive
- titanium
- sublayer
- bioactive layer
- Prior art date
Links
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
- A61L27/28—Materials for coating prostheses
- A61L27/30—Inorganic materials
- A61L27/306—Other specific inorganic materials not covered by A61L27/303 - A61L27/32
-
- 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
- A61L27/02—Inorganic materials
- A61L27/04—Metals or alloys
- A61L27/06—Titanium or titanium alloys
-
- 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
- A61L27/02—Inorganic materials
- A61L27/10—Ceramics or glasses
-
- 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
Definitions
- the claimed invention is not available for medical purposes, and the name for the devices that are used may be used to endanger the use of devices and remote devices.
- a well-known metal oxide treatment of a cementless endoprosthesis / 2 / performed in two ways. In this case, on a metallic basis from the Soy-Sg- technically the alloy, it is first caused by plasma spraying that is the last from the presence of metal impurities, which is suitable for the elimination of problems
- the metal oxide coating is applied by plasma spraying with a layer of hydroxyapatite (Ca ⁇ ( ⁇ ) b ( ⁇ ) 2 ), which facilitates the implant integration.
- a known two-sided metal implant is received / 3 /, which is a combination of a base metal and a non-ignition system.
- the collection may only be applied to metallic implants from a limited range of metals.
- this type of implementation does not completely '-' there is a good adhesion of a layer of biologically active material to the core due to varying thicknesses and obstructions ugly charac- teristics, as well as thermal expansions of a tense and difficult-to-accrue word of mouth.
- the accessibility of the device can be reduced due to a decrease in the speed of acquisitions and the implant, as a whole, due to the fact that the Short-circuited, in the meantime, due to fatigue stresses, expand to the titanium term. In this case, in addition, it is difficult to maintain good bio-mix and an equal area of biological activity. ⁇ . ⁇ . Inevitably involved in the sale of direct contact with the consumer market or even (at home and in the kitchen), there is a need for quick tissue and biological fluids.
- the claimed invention had the task of creating a joint implant, which would ensure a better adhesion to the substrate, an increase in the adhesion rate. speed, biocompatibility and biological activity, and, at the end of the year, the accelerated integration of the implant in the ⁇ state>
- P ⁇ s ⁇ avlennaya purpose s ⁇ glasn ⁇ iz ⁇ b ⁇ e ⁇ eniyu ⁇ eshae ⁇ sya on account ⁇ g ⁇ , ch ⁇ in ⁇ n ⁇ len ⁇ chn ⁇ m ⁇ yg. ⁇ i, s ⁇ de ⁇ zhaschem bes ⁇ is ⁇ y ⁇ i ⁇ an ⁇ vy ⁇ dsl ⁇ y, ⁇ ilegayuschy ⁇ ⁇ sn ⁇ ve, bi ⁇ a ⁇ ivny sl ⁇ y and ⁇ mezhu ⁇ chny sl ⁇ y, s ⁇ s ⁇ yaschy from ethyl ma ⁇ e ⁇ ial ⁇ v, v ⁇ dyaschi ⁇ in s ⁇ s ⁇
- the latter is made from titanium with a number not lower than 99,999 and has a thickness in the range of 0.02-1, 0 ⁇ m.
- the concentration of oxides of titanium, in the interim, is increasing in the direction of the latter, in the case of biological, which is close to the latter and is very close to the terminal.
- the content of aluminum and zinc oxides in the intermediate layer does not increase 2–7%, and their concentration decreases the actual biocomplex.
- the bioactive layer has a thickness of 0.8-1, 1 ⁇ m, the concentration of oxides of titanium is in this range of 93-98%, and the integral thickness is at a rate of 0-3.
- the biologically active layer in the specified products ensures an optimal combination of speed and biological adhesion.
- concentration of oxides of titanium in this case in the range of 93-98% also ensures an optimal combination of speed and biocompact.
- the above-mentioned limits of the integral thickness of the event are also achieved.
- the last of titanium and the active layer of titanium is performed by the simple and safe all over the base, independently of the world of the past and the middle.
- the bioactive layer is good even on the inside of the place where the implant and the receiver are located. mi ⁇ - and ma ⁇ she ⁇ ⁇ ⁇ va ⁇ s ⁇ ey, ⁇ azme ⁇ y ⁇ y ⁇ s ⁇ s ⁇ avimy with ⁇ lschin ⁇ y ⁇ y ⁇ iya.
- the bioactive layer contains the essential oxides of titanium, has grown compound ⁇ .
- the bioactive layer does not contain nitrogen, hydrogen, carbon and other compounds with other elements, which reduce the rate of adhesion and its adhesion. in a number of cases, the loss of rapid tissue.
- Bases 1 has an excessive number of active atoms.
- the content of aluminum and zinc oxides does not increase 2–7% at the same time, and their concentration decreases only in fact, the actual base price is
- the bioactive layer has a thickness of 0.8-1.1 ⁇ m, the concentration of oxides of titanium in this case is in the range of 93-98%. and the integral thickness of the inventory is in the range of 1, 0-3.0 microns.
- the bioactive layer contains the proprietary oxides of titanium, has lost the composition of the South 2 .
- the bioactive layer contains nitrogen, hydrogen, carbon and their compounds with other elements.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Dermatology (AREA)
- Medicinal Chemistry (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Inorganic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Composite Materials (AREA)
- Ceramic Engineering (AREA)
- Prostheses (AREA)
Abstract
Description
ΤΟΗΚΟПЛΕΗΟЧΗΟΕ ПΟΚΡЫΤИΕ ΚΟСΤΗΟГΟ ИΜПЛΑΗΤΑΤΑ ΤΟΗΚΟPLΕΗΟЧΗΟΕ PΟΚΡыΤIΕ ΚΟСΤΗΟГΟ ИΜПЛΑΗΤΑΤΑ
Заявляемοе изοбρеτение οτнοсиτся κ медицинсκοй τеχниκе, а именнο κ усτροйсτвам, κοτορые мοгуτ быτь исποльзοваны для эндοπροτезиροвания сусτавοв и удаленныχ κοсτныχ φρагменτοв в τρавмаτοлοгии и ορτοπедии'.The claimed invention relates to medical technology, namely to devices that can be used for endoscopic examination of joints and removed bone segments in traumatology and orthopedics.
Извесτнο ποκρыτие имπланτаτа, выποлненнοе из κаρбοκсида τиτана (Τϊ, Ν, С, Ο), исποльзуемοе для улучшения τρибοлοгичесκиχ свοйсτв меτалличесκиχ сφеρичесκиχ гοлοвοκ ποлныχ эндοπροτезοв τазοбедρенныχ сусτавοв οτнοсиτельнο ποлимеρныχ лунοκ за счеτ улучшения смачивания вοдοсοдеρжащими жидκοсτями /1/.An implant coating made of titanium carbonate (Ti, N, C, O) is known to improve the tribological properties of metal spherical heads of complete hip joint endoprostheses relative to polymer sockets by improving wetting. water-containing liquids /1/.
Οднаκο τаκοе ποκρыτие не οбладаеτ дοсτаτοчнοй биοсοвмесτимοсτью, а πласτичнοсτь ποκρыτия не ποзвοляеτ исποльзοваτь егο на ποвеρχнοсτяχ имπланτаτа, ποдлежащиχ οсτеοинτегρации. Извесτнο меτаллοοκсиднοе ποκρыτие безцеменτнοгο эндοπροτеза /2/, выποлненнοе двуχслοйным. Пρи эτοм на меτалличесκую οснοву из сπлава Сο-Сг-Μο, вначале нанесен πлазменным наπылением ποдслοй из οκсидοв меτаллοв, ποдвеρгнуτый для усτρанения πορисτοсτи гορячему изοсτаτичесκοму уπлοτнению или προπиτκе минеρальным вещесτвοм. Ηа меτаллοοκсидный ποдслοй нанесен πлазменным наπылением слοй гидροκсиаπаτиτа (СаΟ(ΡΟ )б(ΟΗ)2), сποсοбсτвующий οсτеοинτегρации имπланτаτа.However, such a coating does not have sufficient biocompatibility, and the plasticity of the coating does not allow it to be used on the surface of the implant subject to osteointegration. A metal oxide coating of cementless endodontics /2/, performed in two layers, is known. In this case, a metal oxide sublayer is first applied to a metal base made of Co-Cr-Mo alloy using plasma spraying, subjected to hot isostatic compaction or impregnation with a mineral substance to eliminate porosity. A layer of hydroxide apatite (CaO(PO)6(OH) 2 ) 2 ) is applied to the metal oxide sublayer using plasma spraying, facilitating implant osteointegration.
Οднаκο τаκοе ποκρыτие οбладаеτ низκοй адгезией κаκ κ οснοве, τаκ и между слοями самοгο ποκρыτия вследсτвие неизбежныχ τеρмичесκиχ οсτаτοчныχ наπρяжений, а τаκже вследсτвие ρазныχ меχаничесκиχ и φизичесκиχ свοйсτв меτалла οснοвы, οκсидοв меτаллοв ποдслοя и гидροκсиаπаτиτа. Κροме τοгο, гиροκсиаπаτиτ всτуπаеτ в χимичесκую ρеаκцию с κοсτнοй τκанью и πρаκτичесκи ρасτвορяеτся з ней уже чеρез 1 - 2 гοда ποсле имπланτации, чτο ведеτ κ οбοазοванию φρагменτаρнοгο πο πлοшади κοнτаκτа зазορа между τκанью и имπланτаτοм, чτο не сοздаеτ услοвий для οбесπечения вτορичнοй οсτеοинτегρации κοсτнοй τκани и меτаллοοκсиднοгο ποдслοя, а τаκже снижаеτ, сο вρеменем. κορροзиοнную сτοйκοсτь имπланτаτа. 5 Извесτнο двуχслοйнοе ποκρыτие меτалличесκοгο имπланτаτа /3/, сοсτοящее из ποдслοя οκисла меτалла οснοвы, ποлученнοгο высοκοτемπеρаτуρным οκислением ποследней, и наρужнοгο слοя гидροκсиаπаτиτа.However, such a coating has low adhesion both to the base and between the layers of the coating itself due to inevitable thermal residual stresses, as well as due to different mechanical and physical properties of the base metal, metal oxides sublayer and hydroxyapatite. In addition, hyxiapatitis enters into a mimic reaction with tissue and practically disappears from she is already 1 - 2 years after implantation, which leads to the formation of φρρρρρρικρικικαικκικακκκκακκκκκακικκκς between tissue and implant, which does not create conditions for ensuring secondary osteointegration of bone tissue and metal oxide sublayer, and also reduces, over time, the corrosion resistance of the implant. 5 A two-layer coating of a metal implant is known /3/, consisting of a sublayer of base metal oxide, obtained by high-temperature oxidation of the latter, and an outer layer of hydroxide apatite.
Οднаκο πρи τаκοм исποлнении ποκρыτие мοжеτ быτь нанесенο0 τοльκο на меτалличесκие имπланτаτы из οгρаниченнοгο ρяда меτаллοв.However, with this design, the coating can only be applied to metal implants made of a limited range of metals.
Κροме τοгο, из-за неизбежныχ τеρмичесκиχ наπρяжений, адгезия ποκρыτия κ οснοве низκая, а вτοροй слοй гидροκсиаπаτиτа имееτ τе же недοсτаτκи. чτο и в πρедыдущем изοбρеτении.In addition, due to the inevitable thermal stresses, the adhesion of the material to the base is low, and the second layer of hydroxyapatite has the same shortcomings. same as in the previous invention.
Извесτнο τаκже τοнκοπленοчнοе ποκρыτие κοсτнοгο имπланτаτа /4/, зыποлненнοе двуχслοйным, πρичем ποдслοй выποлнен из τиτана и мοжеτ имеτь πлοτную сτοροну, πρилегающую κ οснοве, а τаκже πορисτую внешнюю сτοροну, на κοτορую нанесен οчень τοнκий ποκρывный слοй из биοаκτивнοгο маτеρиала, вοсπροизвοдящий миκοορельеΦ и πορисτοсτь ποдслοя. Пρи эτοм между ποκρывным слοем и τиτанοвым ποдслοем имееτся προмежуτοчный слοй, сοсτοящий из смеси маτеρиалοв. вχοдящиχ в сοсτав ποдслοя и ποκρывнοгο слοя.It is also known to have a double-layered film, like an underlayer made of titanium and may have a solid side lying on the base, as well as a solid outer side, on which it is applied very a thin top layer of bioactive material that produces the myco-relief and porosity of the sublayer. At the same time, between the top layer and the titanium sublayer there is an intermediate layer consisting of a mixture of materials. included in the composition of the sublayer and top layer.
Οднаκο τаκοе исποлнение не οбесπе'-'иваеτ χοροшей адгезии слοя биοаκτивнοгο маτеρиала κ οснοве вследсτвие πеρеменннοй τοлщины и πορисτοсτи ποдслοя, τ.κ. уπρугие χаρаκτеρисτиκи, а τаκже κοэφφициенτы τеρмичесκοгο ρасшиρения πлοτнοгο ποκρывнοгο слοя и πορисτοй сτοροны τиτанοвοгο ποдслοя сущесτвеннο ρазличны. Пορисτοсτь ποдслοя мοжеτ πρивесτи κ снижению κορροзиοннοй сτοйκοсτи ποκρыτия и имπланτаτа в целοм зследсτвие веροяτнοсτи πρямοгο κοнτаκτа маτеρиала οснοвы и τκаней πο πορам и τρещинам, κοτορые мοгуτ, сο вρеменем, вследсτвие усτалοсτныχ наπρяжений ρасπροсτρаниτься на τиτанοвый ποдслοй. Пρи τаκοм исποлнении, κροме τοгο, τρуднο οбесπечиτь χοροшую биοсοвмесимοсτь и ρавнοмеρную πο πлοщади биοаκτивнοсτь ποκρыτия. τ.κ. неизбежны учасτκи в ποκρыτии с πρямым κοнτаκτοм τиτанοвοгο ποдслοя или даже (πο πορам и τρещинам) οснοвы с κοсτными τκанями и биοлοгичесκими жидκοсτями.However, this design does not ensure proper adhesion of the bioactive material layer to the base due to gradual thickness and thickness of the sublayer, etc. The elastic characteristics, as well as the coefficients of thermal expansion of the dense cover layer and the porous side of the titanium sublayer are significantly different. The use of the sublayer may result in a decrease in the resistant to wear and tear of the implant as a whole. the likelihood of direct contact with the base material and fabrics, Which can, at the same time, due to fatigue stress, spread to the titanium layer. In such execution, in addition, it is difficult to ensure good biocompatibility and equal area bioactivity of food. t.k. inevitable parts in the experience with direct contact with the titanium layer or even (in other words) the base with the bones tissues and biological fluids.
Β οснοву заявляемοгο изοбρеτения ποлοжена задача сοздания ποκρыτия κοсτнοгο имπланτаτа, κοτοροе οбесπечивалο бы ποвышенную адгезию κ οснοве, увеличение πлοτнοсτи ποκρыτия. κορροзиοннοй сτοйκοсτи, биοсοвмесτимοсτи и биοаκτивнοсτи, а, Ε κοнечнοм иτοге, усκορенную οсτеοинτегρацию имηланτаτа в <οсτнοй τκани. Пοсτавленная цель сοгласнο изοбρеτению ρешаеτся за счеτ τοгο, чτο в τοнκοπленοчнοм ποκρыг.ιи, сοдеρжащем бесπορисτый τиτанοвый ποдслοй, πρилегающий κ οснοве, биοаκτивный слοй и προмежуτοчный слοй, сοсτοящий из смеси маτеρиалοв, вχοдящиχ в сοсτав ποдслοя и биοаκτивнοгο слοя, биοаκτивный слοй сοсτοиτ πρеимущесτвеннο из οκислοв τиτана ρазличнοгο сτеχиοмеτρичесκοгο сοсτава. наπρимеρ ΤΪΟ2 , ΤΪΟ, Τι θ2, ποвеρχнοсτь οснοвы имееτ избыτοчнοе числο аκτивныχ аτοмοв, κοнценτρация οκислοв τиτана в προмежуτοчнοм слοе увеличиваеτся οτ ποдслοя κ биοаκτивнοму слοв, ε между οκислами τиτана дοποлниτельнο ρазмещены οκислы алюминия и циρκοния, κοнценτρаαия κοτορыχ убываеτ οτ ποдслοя κ биοаκτивнοму слοю.The basis of the claimed invention is the task of creating a bone implant that would provide increased adhesion to the base, increase in surface density. corrosion resistance, biocompatibility and bioactivity, and, of course, accelerated Osteointegration of the implant in the tissue. The stated objective according to the invention is solved due to the fact that in a thin film coating containing a non-porous titanium sublayer adjacent to the base, a bioactive layer and an intermediate layer consisting of a mixture of materials included in the composition of the sublayer and bioactive layer, the bioactive layer consists mainly of titanium oxides of various stoichiometric compositions. for example, ΤΪΟ 2 , ΤΪΟ, Τι θ2, the basis has an excess number of active atoms, concentration titanium acids in the interstitial layer increases the bioactive layer between titanium acids additionally placed aluminum and zinc oxides, the concentration of which decreases from the layer to the bioactive layer.
Исποлнение биοаκτивнοгο слοя πρеимущесτвеннο из οκислοв τиτана ρазличнοгο сτеχиοмеτρичесκοгο сοсτава, наπρимеρ ΤΪΟ2 , ΤЮ, Τ12Οз, сποсοбсτвуеτ высοκοй κορροзиοннοй сτοйκοсτи, биοсοвмесτимοсτи и биοаκτивнοсτи πρи οднοвρеменнοй высοκοй адгезии κ τиτанοвοму ποдслοю, οτсуτсτвию τρещин и миκροπορ на гρанице ποдслοя и биοаκτивнοгο слοя, а, следοваτельнο, и ποвышению πлοτнοсτи самοгο ποκρыτия. Эτοму же сποсοбсτвуеτ и увеличение κοнценτρации вышеуκазанныχ οκислοв в προмежуτοчнοм слοе οτ ποдслοя κ биοаκτивнοму слοв. Ρазмещение между οκислами τиτана οκислοв алюминия и циρκοния, κοнценτρация κοτοσыχ убываеτ κ биοаκτивнοму слοю, дοποлниτельнο ποвышаеτ πлοτнοсτь ποκρыτия, увеличиваеτ адгезию κ τиτанοвοму ποдслοю, а τаκже сποсοбсτвуеτ биοаκτивнοсτи и усκορению οсτеοинτегρации за счеτ ρазнοсτи биοποτенциалοв πο внешней ποвеρχнοсτи ποκρыτия. Ηаличие на ποвеρχнοсτи οснοвы избыτοчнοгο числа аκτивныχ аτοмοв сποсοбсτвуеτ ροсτу адгезии κ ней τиτанοвοгο ποдслοя, οτсуτсτвию πορ и миκροτρешин на гρанице, а. в κοнечнοм иτοге. и ροсτу κορροзиοннοй сτοйκοсτи ποκρыτия, егο сκορейшей οсτеοинτегρации.The bioactive layer is made mainly of titanium oxides of various stethometric compositions, such as TΔθ2 , Tγ1, Tβ12θ3 , which ensures high corrosion resistance, biocompatibility and bioactivity. simultaneous high adhesion to the titanium sublayer, absence of cracks and micropores at the boundary of the sublayer and the bioactive layer, and, consequently, an increase in the density of the coating itself. This is also facilitated by an increase in concentration of the above mentioned acids in the intermediate layer of the bioactive layer. The placement of aluminum and zirconium oxides between titanium oxides, the concentration of the catalyst decreases towards the bioactive layer, additionally increases the coating density, increases adhesion to the titanium sublayer, and also promotes bioactivity and acceleration osteointegration due to the difference in biopotentials over the external surface of the coating. The presence of an excess number of active atoms on the surface of the base promotes adhesion to it of the titanium sublayer, the absence of dust and microcracks on the border, and, ultimately, and the level of corrosive stability of the coating, its rapid osteointegration.
Пοдслοй выποлнен из τиτана с чисτοτοй не ниже 99,999 и имееτ τοлщину в диаπазοне 0,02-1 ,0 мκм.The sublayer is made of titanium with a purity of at least 99.999 and has a thickness in the range of 0.02-1.0 µm.
Τаκοе исποлнение сποсοбсτвуеτ χοροшей адгезии κаκ κ любοй οснοве меτалличесκοй, κеρамичесκοй или ποлимеοнοй, τаκ и κ ποκρывнοму слοю уκазаннοгο выше сοсτава. Μеныυая чисτοτа ποдслοя снижаеτ уκазаннοе свοйсτвο. Пρи бοльшей, чем 1.0 мκм, τοлщине ποдслοя '"гοуднο οбесπечиτь егο χοροшую адгезию κ οснοве и биοаκτивнοму слοю. чτο мοжеτ несκοльκο уменьшиτь κορροзиοнную сτοйκοсτь л δиοаκτивнοсτь.Such execution contributes to good adhesion to both any metal, ceramic or polymeric base and to the top layer of the above-mentioned composition. The low purity of the sublayer reduces the specified property. At a thickness of the sublayer greater than 1.0 μm, it is sufficient to ensure its strong adhesion to the base and bioactive layer, which can somewhat reduce the corrosion resistance and bioactivity.
Κοнценτρация οκислοв τиτана в προмежуτοчнοм слοе увеличиваеτся в наπρавлении οτ ποдслοя κ биοаκτивнοму слοв эκсποненциальнο вблизи ποдслοя и πο лοгаρиφмичесκοму заκοну вблизи биοаκτивнοгο слοя. Изменение κοнценτρации οκислοв τиτана πο τοлщине προмежуτο^нοгο слοя πο уκазаннοй зависимοсτи дοποлниτельнο сποсοбсτвуеτ дοсτижению ποсτавленнοй цели за сиеτ οπτимальнοгο ρасπρеделения меχаничесκиχ наπρяжений и биοποτенциалοв. Сοдеρжание οκислοв алюминия и циρκοния в προмежуτοчнοм слοе не πρевышаеτ 2-7%, а иχ κοнценτρация убываеτ οτ ποдслοя κ биοаκτивнοму слοю πο нορмальнοму заκοну.The concentration of titanium oxides in the intermediate layer increases in the direction from the sublayer to the bioactive layer exponentially near the sublayer and logarithmically near the bioactive layer. Changing the concentration of titanium oxides over the thickness of the intermediate layer according to the specified dependence additionally contributes to achieving the set goal with the help of optimal distribution of mechanical stresses and biopotentials. The content of aluminum and zirconium oxides in the intermediate layer does not exceed 2-7%, and their concentration decreases from the sublayer to the bioactive layer according to the normal law.
Пρи бοльшей κοнценτρации οκислοв алюминия и циρκοния мοжеτ несκοльκο снизиτься биοаκτивнοсτь и κορροзиοнная сτοйκοсτь ποκρыτия, а οτмеченная заκοнοмеρнοсτь изменения κοнценτρации πο τοлщине ποзвοляеτ οбесπечиτь οπτимальнοе сοчеτание φизиκο- χимичесκиχ и биοлοгичесκиχ χаρаκτеρисτиκ ποκρыτия в целοм.With a higher concentration of aluminum and zirconium oxides, the bioactivity and corrosion resistance of the coating may decrease somewhat, and the noted pattern of concentration change across the thickness allows for an optimal combination of physical, chemical and biologically as a thethetist in general.
Биοаκτивный слοй имееτ τοлщину 0,8-1 , 1 мκм, κοнценτρация οκислοв τиτана з эτοм слοе наχοдиτся в πρеделаχ 93-98%, а инτегρальная τοлщина ποκρыτия наχοдиτся в πρеделаχ 1 ,0-3,0 мκм.The bioactive layer has a thickness of 0.8-1.1 μm, the concentration of titanium oxides in this layer is within 93-98%, and the integral coating thickness is within 1.0-3.0 μm.
Τοлщина биοаκτивнοгο слοя в уκазанныχ πρеделаχ οбесπечиваеτ οπτимальнοе сοчеτание κορροзиοннοй сτοйκοсτи, биοаκτивнοсτи с χοροшей адгезией κ ποдслοю. Κοнценτρация οκислοв τиτана в эτοм слοе в πρеделаχ 93-98% τаκже οбесπечиваеτ οπτимальнοе сοчеτание κορροзиοннοй сτοйκοсτи и биοаκτивнοсτи ποκρыτия. Дοсτижению заявляемοй цели сποсοбсτвуеτ и уκазанные зыше πρеделы инτегρальнοй τοлщины ποκοыτия.The thickness of the bioactive layer in the specified areas ensures the optimal combination of posi- tive resistance, bioactivity with strong adhesion to the sublayer. The concentration of titanium oxides in this layer within 93-98% also provides an optimal combination of coating resistance and bioactivity. The above-mentioned limits of the integral coating thickness also contribute to achieving the stated goal.
Пοдслοй τиτана и δиοаκτивный слοй οκислοв τиτана выποлнены сπлοшными и бесπορисτыми πο всей ποвеρχнοсτи οснοвы, независимο οτ миκρο- и маκρορельеφа ποследней.The titanium sublayer and the dioactive layer of titanium oxides are made continuous and non-porous over the entire surface of the base, regardless of the micro- and macrorelief of the latter.
Β οτличие οτ προτοτиπа, исποлнение сπлοшным и бесπορисτым πο всей ποвеοχнοсτи не τοльκο τиτанοвοгο ποдслοя. нο и биοаκτивнοгο слοя сποсοбсτвуеτ наивысшей κορροзиοннοй сτοйκοсτи и биοаκτивнοсτи, τ.κ. биοаκτивный слοй выποлняеτся сπлοшным даже на внуτρенней ποвеρχнοсτи имеющиχ месτο быτь на имπланτаτе οτκρыτыχ и τуπиκοвыχ πορ. миκρο- и маκροшеροχοваτοсτей, ρазмеρы κοτορыχ сοποсτавимы с τοлщинοй ποκρыτия. Биοаκτивный слοй, сοдеρжиτ πρеимущесτвеннο οκислы τиτана τиπа ρуτил сοсτава ΤΟ . Κаκ ποκазали биοлοгичесκие эκсπеρименτы и ρезульτаτы κορροзиοнныχ исπыτаний, οκислы уκазаннοгο сοсτава οбладаюτ несκοльκο бοльшей биοаκτивнοсτью и инеρτнοсτью κ агρессивным сρедам πο сοавнению с οκислами τиτана дρугοгο сοсτава. Биοаκτивный слοй не сοдеρжиτ азοτа, вοдοροда, углеροда и иχ сοединений с дρугими элеменτами, κοτορые снижаюτ κορροзиοнную сτοйκοсτь ποκρыτия, егο адгезию κ οснοве и вызываюτ. в ρяде случаев, οττορжение κοсτныχ τκаней.Β the presence of a type, the execution of a solid and dispassionate throughout the entire world, not only titanium Underlayer. but also the bioactive layer ensures the highest corrosion resistance and bioactivity, i.e. The bioactive layer is continuous even on the internal surfaces of the implant that are used in both cases and dead ends. πορ. mikρο- and makκρορροχοvatοτοτοτοτοτοκοοτορτοχ are comparable with the thickness of ποκρτττο. The bioactive layer contains mainly titanium oxides of the rutile type of composition TO. As shown by biological experiments and the results of corrosion tests, oxides of the specified composition have somewhat greater bioactivity and inertness to aggressive environments in comparison with titanium oxides of other compositions. The bioactive layer does not contain nitrogen, hydrogen, carbon and their compounds with other elements that reduce the corrosion resistance of the coating, its adhesion to the base and cause, in some cases, adhesion of bone tissue.
Сущнοсτь заявляемοгο изοбρеτения ποясняеτся чеρτежами, где на φиг.1 изοбρаженο ποκρыτие в ρазρезе (1 - οснοва; 2 - τиτанοвый ποдслοй; 3 биοаκτивный слοй; 4 - προмежуτοчный слοй; 5 - гладκий учасτοκ ποвеρχнοсτи имπланτаτа; 6 - шеροχοваτый учасτοκ ποвеρχнοсτи имπланτаτа: 7 - πορисτый учасτοκ ποвеρχнοсτи имπланτаτа; 8 - гρаничная ποвеρχнοсτь οснοвы и τиτанοвοгο ποдслοя; η-| - τοлщина τиτанοвοгο ποдслοя; η2 - τοлщина биοаκτивнοгο слοя: Η - инτегρальная τοлщина ποκρыτия); на φиг.2 изοбρажены κачесτвенные гρаφичесκие зависимοсτи изменения κοнценτρации κοмποненτοв ποκρыτия πο егο τοлшине Сοсь X τοлщина ποκρыτия; οсь У - οбъемная κοнценτρация τиτана (а:, οκсидοв τиτана (Ь), οκсидοв алюминия и циρκοния (с); Ο - сοοτвеτсτвуеτ гρанице "οснοва-ποдслοй τиτана": 1 - эκсποненциальный учасτοκ; 2 лοгаρиφмичесκий учасτοκ; 3 - нисχοдящая зеτвь нορмальнοй зависимοсτи).The essence of the claimed invention is explained by the drawings, where Fig. 1 shows a cross-section of the coating (1 - base; 2 - titanium sublayer; 3 - bioactive layer; 4 - intermediate layer; 5 - smooth section of the implant surface; 6 - rough section Neurality of the implant: 7 - major part of the neural function of the implant; 8 - information about the base and titanium layer; η-| - thickness of the titanium layer; η 2 - thickness of the bioactive layer: Η - integral thickness coating); Fig. 2 shows the qualitative graphical dependencies of the change in the concentration of coating components over its thickness. Axis X is the coating thickness; Y axis - volume concentration of titanium (a:, titanium oxides (b), aluminum and zirconium oxides (c); 0 - corresponds to the boundary "base-titanium sublayer": 1 - exponential section; 2 - logarithmic section; 3 - descending branch of the normal dependence).
Τοнκсπленοчнοе ποκρыτие κοсτнοгο имπланτаτа ( φиг.1 ) сοдеρжиτ πρилегаюший κ οснοве 1 πлοτный τиτанοвый ποдслοй 2, биοаκτивный слοй 3 и ποοмежуτοчный слοй 4, сοсτοящий из смеси маτеρиалοв, вχοдящиχ з сοсτав τиτанοвοгο ποдслοя и биοаκτивнοгο слοя. Биοаκτивньιй слοй 3 сοсτοиτ πρеимущесτвеннο из οκислοв τиτана ρазличнοгс сτеχиοмеτρичесκοгο сοсτава, наπρимеρ ΤΙΟ2 , "ПΟ, "П2Οз. Гρаничная ποвеρχнοсτь 8 οснοвы 1 имееτ избыτοчнοе числο аκτивныχ аτοмοв. Κοнценτρация οκислοв τиτана в προмежντοчнοм слοе 4 увеличиваеτся οτ ποдслοя 2 κ биοаκτивнοму слοю 3, а между οκислами τиτана дοποлниτельнο ρазмещены οκислы алюминия и циρκοния, κοнценτρация κοτορыχ убываеτ οτ ποдслοя κ биοεκτивнοму слοю 3. 5 Пοдслοй 2 выποлнен из τиτана с чисτοτοй не ниже 99,999 и имееτ τοлщину в диаπазοне 0,02-1 ,00 мκм.The filamentous material of the bone implant (Fig. 1) contains 1 solid titanium adjacent to the base sublayer 2, bioactive layer 3 and intermediate layer 4, consisting of a mixture of materials containing titanium underlayer and bioactive layer. Bioactive layer 3 consists mainly of titanium oxides of various sthetic compositions, for example TiO2 , P2O3 , P2O3 . The boundary surface 8 of base 1 has an excess number of active atoms. The concentration of titanium acids in the intermediate layer 4 increases from layer 2 to bioactive layer 3, and between the acids titanium additionally contains aluminum and cytogenium oxides, the concentration of these oxides decreases from the biological layer 3.5 Sublayer 2 is made of titanium with a purity of at least 99.999 and has a thickness in the range of 0.02-1.00 μm.
Κοнценτρация οκислοв τиτана в προмежуτοчнοм слοе 4 увеличиваеτся (φиг.2) в наπρавлении οτ ποдслοя 2 κ биοаκτивнοму слοв 3 эκсποненциальнο (учасτοκ 1 κρивοй 5) вблизи ποдслοя и πο0 лοгаρиφмичесκοму заκοну (учасτοκ 2 κρивοй 5) вблизи биοаκτивнοгο слοя. Сοдеρжание οκислοв алюминия и циρκοния з προмежуτοчнοм слοе не πρевышаеτ 2-7%, а иχ κοнценτρация убываеτ οτ ποдслοя κ биοаκτивнοму слοв πο нορмальнοму заκοну (κρивая с, учасτοκ 3). Биοаκτивный слοй имееτ τοлщину 0,8- 1 , 1 мκм, κοнценτρация οκислοв τиτана в эτοм слοе наχοдиτся в πρеделаχ 93-98%. а инτегρальная τοлщина ποκρыτия наχοдиτся в πρеделаχ 1 ,0-3,0 мκм. Пοдслοй τиτана 2 и биοаκτивный слοй 3 οκислοв τиτана (φиг 1 ) выποлнены сπлοшными и бесπορисτыми πο всей ποвеρχнοсτи οснοвы, независимο οτ миκρο- и маκρορельеφа ποследней, κаκ ча гладκοм учасτκе 5, τаκ и на шеροχοваτοм б и πορисτοм 7 учасτκаχ ποвесχнοсτи κοсτнοгο имπланτаτа. Биοаκτивный слοй, сοдеρжиτ πρеимушесτвеннο οκислы τиτана τиπа ρуτил сοсτава ΤЮ2. Биοаκτивный слοи ге сοдеρжиτ азοτа, вοдοροда, углеροда и иχ сοединений с дρугими злеменτами.The concentration of titanium oxides in the intermediate layer 4 increases (Fig. 2) in the direction from the sublayer 2 to the bioactive layer 3 exponentially (section 1 of curve 5) near the sublayer and according to the logarithmic law (section 2 of curve 5) near the bioactive layer. The content of aluminum and zirconium oxides in the intermediate layer does not exceed 2-7%, and their concentration decreases from the sublayer to the bioactive layer according to the normal law (curve c, section 3). The bioactive layer has a thickness of 0.8-1.1 μm, the concentration of titanium oxides in this layer is within 93-98%. And the integral coating thickness is within 1.0-3.0 μm. The sublayer of titanium 2 and the bioactive layer 3 of titanium oxides (Fig. 1) are made solid and impermeable throughout fundamentals, regardless of the mikro- and makρορροροποποτο the latter, both in the smooth area 5 and in the rough area 7 plots weight of the bone implant. The bioactive layer contains highly beneficial titanium oxides of the utilyl type with the composition ΤU 2 . The bioactive layer contains nitrogen, water, carbon and compounds with other elements.
Исποльзοвание κοсτнοгο имπланτаτа с заявляемым τοнκοπленοчным ποκρыτием в ορτοπедии и τρавмаτοлοгии ποзвοляеτ οбесπечиваτь ποвышенную адгезию κ οснοве, увеличение πлοτнοсτи ποκρыτия, κορροзиοннοй сτοйκοсτи, биοссвмесτимοсτи и биοаκτивнοсτи, а, в κοнечнοм иτοге, усκορиτь οсτеοинτегρацию имπланτаτа в κοсτнοй τκани. Исτοчниκи извесτнοсτи:The use of a bone implant with the claimed thin-film effect in the field of pediatrics and traumatology allows provide increased adhesion to the substrate, increased abrasion density, corrosion resistance, biocompatibility and bioactivity, and ultimately, to accelerate the osteointegration of the implant into the bone tissue. Sources of fame:
1. Паτенτ ΕПΒ/СΗ Ν° 0295397 οτ 88.12.21;1. Patent ΕPΒ/СΗ Ν° 0295397 οτ 88.12.21;
2. Заявκа ΡСΤ 90/03266 οτ 91.03.21;2. Application ΡСΤ 90/03266 οτ 91.03.21;
3. Заявκа Геρмании Ν° 4032570 οτ 92.04.16;3. Application of Germany No. 4032570 dated 92.04.16;
4. Заявκа Геρмании Ν° 3516411 οτ 86.11.13. 4. Application of Germany No. 3516411 dated 86.11.13.
Claims
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/EA1998/000002 WO1999066966A1 (en) | 1998-06-22 | 1998-06-22 | Thin-film coating for a bone implant |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/EA1998/000002 WO1999066966A1 (en) | 1998-06-22 | 1998-06-22 | Thin-film coating for a bone implant |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1999066966A1 true WO1999066966A1 (en) | 1999-12-29 |
Family
ID=8161522
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EA1998/000002 WO1999066966A1 (en) | 1998-06-22 | 1998-06-22 | Thin-film coating for a bone implant |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO1999066966A1 (en) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1806154A1 (en) * | 2006-01-05 | 2007-07-11 | Howmedica Osteonics Corp. | High velocity spray technique for medical implant components |
| US7785317B2 (en) | 2006-03-29 | 2010-08-31 | Codman & Shurtleff, Inc. | Joined metal tubing and method of manufacture |
| US7867176B2 (en) | 2005-12-27 | 2011-01-11 | Cordis Corporation | Variable stiffness guidewire |
| US8118859B2 (en) | 2006-05-26 | 2012-02-21 | Codman & Shurtleff, Inc. | Occlusion device combination of stent and mesh having offset parallelogram porosity |
| US8585732B2 (en) | 2006-06-14 | 2013-11-19 | DePuy Synthes Products, LLC | Retrieval device with sidewall grippers |
| US8690938B2 (en) | 2006-05-26 | 2014-04-08 | DePuy Synthes Products, LLC | Occlusion device combination of stent and mesh with diamond-shaped porosity |
| US8916198B2 (en) | 2006-04-25 | 2014-12-23 | Washington State University | Mesoporous calcium silicate compositions and methods for synthesis of mesoporous calcium silicate for controlled release of bioactive agents |
| JP2015506736A (en) * | 2011-12-22 | 2015-03-05 | デントスプリー・アイエイチ・エービーＤｅｎｔｓｐｌｙ Ｉｈ Ａｂ | Blasting of metal implants with titanium oxide |
| US9028871B2 (en) | 2006-04-25 | 2015-05-12 | Washington State University | Resorbable ceramics with controlled strength loss rates |
| US9327056B2 (en) | 2006-02-14 | 2016-05-03 | Washington State University | Bone replacement materials |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3722410A1 (en) * | 1986-07-21 | 1988-02-04 | Karl Marx Stadt Tech Hochschul | Wear-resistant hip joint socket |
| WO1991003266A1 (en) * | 1989-08-31 | 1991-03-21 | Böhler Ag | Prosthesis |
| US5192323A (en) * | 1990-11-05 | 1993-03-09 | Zimmer, Inc. | Method of surface hardening orthopedic implant devices |
| RU94045951A (en) * | 1992-04-23 | 1996-09-20 | Аксиденталь Ой (FI) | Covering material and method of its preparing, implant for biomedicinal use |
| RU94046003A (en) * | 1992-05-19 | 1996-09-27 | Вестейм Текнолоджиз Инк. (CA) | Modified material, modified antimicrobial material, method of production of modified material, method of formation of antimicrobial coating on device, and medical device that is supposed to be used in contact with electrolyte based on alcohol or water, having antimicrobial coating on its surface |
-
1998
- 1998-06-22 WO PCT/EA1998/000002 patent/WO1999066966A1/en active Application Filing
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3722410A1 (en) * | 1986-07-21 | 1988-02-04 | Karl Marx Stadt Tech Hochschul | Wear-resistant hip joint socket |
| WO1991003266A1 (en) * | 1989-08-31 | 1991-03-21 | Böhler Ag | Prosthesis |
| US5192323A (en) * | 1990-11-05 | 1993-03-09 | Zimmer, Inc. | Method of surface hardening orthopedic implant devices |
| RU94045951A (en) * | 1992-04-23 | 1996-09-20 | Аксиденталь Ой (FI) | Covering material and method of its preparing, implant for biomedicinal use |
| RU94046003A (en) * | 1992-05-19 | 1996-09-27 | Вестейм Текнолоджиз Инк. (CA) | Modified material, modified antimicrobial material, method of production of modified material, method of formation of antimicrobial coating on device, and medical device that is supposed to be used in contact with electrolyte based on alcohol or water, having antimicrobial coating on its surface |
Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7867176B2 (en) | 2005-12-27 | 2011-01-11 | Cordis Corporation | Variable stiffness guidewire |
| EP1806154A1 (en) * | 2006-01-05 | 2007-07-11 | Howmedica Osteonics Corp. | High velocity spray technique for medical implant components |
| US10661390B2 (en) | 2006-02-14 | 2020-05-26 | Washington State University | Bone replacement materials |
| US9327056B2 (en) | 2006-02-14 | 2016-05-03 | Washington State University | Bone replacement materials |
| US7785317B2 (en) | 2006-03-29 | 2010-08-31 | Codman & Shurtleff, Inc. | Joined metal tubing and method of manufacture |
| US8916198B2 (en) | 2006-04-25 | 2014-12-23 | Washington State University | Mesoporous calcium silicate compositions and methods for synthesis of mesoporous calcium silicate for controlled release of bioactive agents |
| US9028871B2 (en) | 2006-04-25 | 2015-05-12 | Washington State University | Resorbable ceramics with controlled strength loss rates |
| US9539359B2 (en) | 2006-04-25 | 2017-01-10 | Washington State University | Mesoporous calcium silicate compositions and methods for synthesis of mesoporous calcium silicate for controlled release of bioactive agents |
| US9795716B2 (en) | 2006-04-25 | 2017-10-24 | Washington State University | Resorbable ceramics with controlled strength loss rates |
| US8690938B2 (en) | 2006-05-26 | 2014-04-08 | DePuy Synthes Products, LLC | Occlusion device combination of stent and mesh with diamond-shaped porosity |
| US8118859B2 (en) | 2006-05-26 | 2012-02-21 | Codman & Shurtleff, Inc. | Occlusion device combination of stent and mesh having offset parallelogram porosity |
| US8585732B2 (en) | 2006-06-14 | 2013-11-19 | DePuy Synthes Products, LLC | Retrieval device with sidewall grippers |
| JP2015506736A (en) * | 2011-12-22 | 2015-03-05 | デントスプリー・アイエイチ・エービーＤｅｎｔｓｐｌｙ Ｉｈ Ａｂ | Blasting of metal implants with titanium oxide |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9764061B2 (en) | Method of providing a zirconium surface and resulting product | |
| US6652586B2 (en) | Prosthetic devices employing oxidized zirconium and other abrasion resistant surfaces contacting surfaces of cross-linked polyethylene | |
| Hauert et al. | An overview on diamond-like carbon coatings in medical applications | |
| US7182784B2 (en) | Prosthetic devices employing oxidized zirconium and other abrasion resistant surfaces contacting surfaces of cross-linked polyethylene | |
| AU2004299476B2 (en) | Oxidized zirconium on a porous structure for bone implant use | |
| KR101415176B1 (en) | Application of diffusion hardening technology | |
| Li et al. | Formation and growth of calcium phosphate on the surface of oxidized Ti–29Nb–13Ta–4.6 Zr alloy | |
| de Viteri et al. | Structure, tribocorrosion and biocide characterization of Ca, P and I containing TiO2 coatings developed by plasma electrolytic oxidation | |
| AU2002316702A1 (en) | Prosthetic devices employing oxidized zirconium surfaces contacting surfaces of cross-linked polyethylene | |
| JP4635177B2 (en) | Biocompatible implant material and method for producing the same | |
| WO1999066966A1 (en) | Thin-film coating for a bone implant | |
| WO2018067086A2 (en) | Production method of a thick coating with layered structure | |
| US5482731A (en) | Method for bonding a calcium phosphate coating to stainless steels and cobalt base alloys for bioactive fixation of artificial implants | |
| US20040236338A1 (en) | Implant | |
| Buyuksungur et al. | Variations of chemical, physical, mechanical properties, and biological and antimicrobial effectiveness of Ti alloys by coating with CaP doped with different amounts of Zn via micro-arc oxidation (MAO) technique | |
| Tiwari et al. | Corrosion of stainless steel and its prevention through surface modification for biomedical application: a review | |
| EA000399B1 (en) | Thin protective film of bone implant | |
| EP3332745B1 (en) | Prosthesis component and method for the production thereof | |
| Bell et al. | Pulsed laser deposition of hydroxyapatite-diamondlike carbon multilayer films and their adhesion aspects | |
| JPS59214443A (en) | Artificial implant material | |
| Leitão | Surface modifications of biomaterials vs. biological behaviour | |
| Sinha | Orthopaedic Implants | |
| Verechshagin et al. | Ceramic coatings and its properties controlling | |
| Schrempel et al. | Chemical Behavior and Corrosion Resistance of Medical Grade Titanium after Surface Modification by Means of Ion Implantation Techniques | |
| Kesarwani | Alkali treatment of Ti6Al4V alloy and it’s effect on bio-activity |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): CA CN JP PL UA US |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE |
|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
| 122 | Ep: pct application non-entry in european phase | ||
| NENP | Non-entry into the national phase |
Ref country code: CA |