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
  • A61L27/02—Inorganic materials
  • A61L27/12—Phosphorus-containing materials, e.g. apatite
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
  • A61L27/28—Materials for coating prostheses
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
  • A61C5/00—Filling or capping teeth
  • A61C5/70—Tooth crowns; Making thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
  • A61C8/00—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools
  • A61C8/0012—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools characterised by the material or composition, e.g. ceramics, surface layer, metal alloy
  • A61C8/0013—Means to be fixed to the jaw-bone for consolidating natural teeth or for fixing dental prostheses thereon; Dental implants; Implanting tools characterised by the material or composition, e.g. ceramics, surface layer, metal alloy with a surface layer, coating
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K6/00—Preparations for dentistry
  • A61K6/80—Preparations for artificial teeth, for filling teeth or for capping teeth
  • A61K6/831—Preparations for artificial teeth, for filling teeth or for capping teeth comprising non-metallic elements or compounds thereof, e.g. carbon
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
  • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
  • A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
  • A61L27/54—Biologically active materials, e.g. therapeutic substances
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • 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
  • A61L2300/412—Tissue-regenerating or healing or proliferative agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
  • A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
  • A61L2300/606—Coatings
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L2420/00—Materials or methods for coatings medical devices
  • A61L2420/06—Coatings containing a mixture of two or more compounds
• • 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 invention generally relates to implant technology and, preferably to dental implant technology. More specifically, the present invention relates to a particular agent for use in improving or promoting osseointegration or soft tissue sealing of a ceramic or metallic implant, to the use of the particular agent for producing a coating on a metallic or ceramic implant, to a metallic or ceramic implant provided with a coating of said particular agent, and to a kit for use in a method of installing a ceramic or metallic implant.
• metallic or ceramic implants are used, for example, in the orthopedic, spine, maxillofacial and dental area .
• cement fixation In the early stages of implant technology a stable and long lasting fixation of an implant in bone was tried to be achieved by cementation.
• the cement forms an interface between bone and metal, and there was no direct bone contact to the metal surface.
• cement fixation has several disadvantages, such as an insufficient life time and
• the dental implant process is carried out in two stages. At first the implant is inserted into the jaw bone. The gums are then closed up to allow healing to take place. Usually, it takes about 3 to 6 months for the implant to firmly integrate in the bone. After this healing period the artificial tooth crown can be attached to the implant thereby finalizing the implant procedure.
• WO 00/44305 describes an osteophilic implant provided with a roughened, hydroxylated and hydrophilic surface which is at least sealed in a gas-tight and liquid- tight covering.
• the interior of said covering is provided with an inert atmosphere, preferably consisting of nitrogen, oxygen and/or inert gas and/or at least partially filled with purified water which optionally contains additives.
• an inert atmosphere preferably consisting of nitrogen, oxygen and/or inert gas and/or at least partially filled with purified water which optionally contains additives.
• the object to be solved by the present invention is the provision of an agent having the ability of improving or promoting osseointegration of an implant, such as a dental implant, as well as the provision of an implant having excellent osseointegration properties.
• the present inventor has surprisingly found that the presence of citrate, citric acid, phosphate, dextrose and adenine on an implant' s surface induces blood protein coating on an implant's surface, platelet activation and a tight fibrin fiber connection to the implant surface.
• These effects i.e. an improved blood protein coating, an improved platelet activation and a tight fibrin fiber connection, are basic requirements for an excellent osseointegration and soft tissue sealing of an implant.
• the present invention relates to an agent for use in improving or promoting osseointegration or soft tissue sealing of a ceramic or metallic implant, wherein the agent comprises trisodium citrate, citric acid, monobasic sodium phosphate, dextrose, and adenine.
• the present invention relates to the use of an agent for producing a coating on a ceramic or metallic implant, wherein the agent comprises trisodium citrate, citric acid, monobasic sodium phosphate, dextrose, and adenine .
• the present invention relates to a ceramic or metallic implant characterized in that the ceramic or metallic implant is provided with at least one coating, wherein the coating is obtainable by immersing the ceramic or metallic implant in an aqueous solution comprising trisodium citrate, citric acid, monobasic sodium phosphate, dextrose, and adenine.
• the present invention relates to a kit for use in a method of installing a ceramic or metallic implant wherein the kit comprises a ceramic or metallic implant, trisodium citrate, citric acid, monobasic sodium phosphate, dextrose and adenine.
• an agent according to the invention promotes osseointegration since its primary use is as an anticoagulant when mixed with blood.
• the dental implant is a bone level implant by the company "Institut Straumann AG" and has a sand-blasted and acid etched surface.
• the dental implant is a bone level implant by the company "Institut Straumann AG" and has a sand-blasted and acid etched surface.
• the abutment is a zirconium oxide-type abutment and has a rather polished, machined surface.
• the abutment is a zirconium oxide-type abutment and has a rather polished, machined surface .
• the dental implant has a porous and, thus, rather rough surface texture as compared with the machined surface of the abutment shown in Figs. 2a and 2b.
• the dental implant has a porous and, thus, rather rough surface texture.
• the dental implant has a porous and smooth surface texture as compared with the machined surface of the abutment shown in Figs. 2a and 2b.
• the dental implant has a porous and, thus, rather rough surface texture .
• Fig. 5 shows a dental implant in a side view.
• Fig. 6 shows an abutment in a side view.
• the present invention provides an agent for use in a method of improving or promoting osseointegration or soft tissue sealing of a ceramic or metallic implant 1, wherein the agent comprises trisodium citrate, citric acid, monobasic sodium phosphate, dextrose and adenine.
• the agent is dissolved in water forming an aqueous solution.
• this aqueous solution for use in improving or promoting osseointegration or soft tissue sealing of a ceramic or metallic implant comprises:
• Such an aqueous solution (in the following also referred to as “the coating solution”) as defined above is preferred because an aqueous solution containing 26.3 g/1 of trisodium citrate, 3.27 g/1 of citric acid, 2.22 g/1 monobasic sodium phosphate, 31.9 g/1 dextrose and 0.275 g/1 adenine is a solution already approved by the FDA and the European authorities.
• a solution so-called CPDA-1 solution, is established as an anticoagulant-preservative and adjuvant for blood bags to enable storage for 35 days without substantial loss of blood cell vitality.
• the solution for use according to the present invention is a 5 to 40 vol.-% solution of the above-mentioned CPDA-1 solution. According to the most preferred embodiment it is used a 10 to 20 vol.-% solution of the above-mentioned CPDA-1 solution.
• an aqueous solution consisting of 2.63 to 5.26 g/1 of trisodium citrate, 0.327 to 0.654 g/1 of citric acid, 0.222 to 0.444 g/1 of monobasic sodium phosphate, 3.19 to 6.38 g/1 of dextrose, and 0.0275 to 0.055 g/1 of adenine, and the rest is water.
• the "implant” according to the present invention can be any ceramic or metallic implant known in the art which would benefit from improved osseointegration or heal-in to body tissue.
• the term "implant” specifically includes or is adapted to carry any dental support component, such as a dental implant, e.g. a load-bearing dental implant, dental bridges, PIBs (implant support bridges), overdenture bars, abutments, and cover screws.
• Ceramic or metallic implants are usually made of titanium, titanium alloys, zirconium alloys, titanium ceramic bodies or zirconium ceramic bodies.
• the preferably used dental support component is usually made of titanium, cobalt chromium although other materials may be used, such as zirconium oxide, aluminium oxide etc.
• the outer surface of the implant, including the dental support is usually made of titanium, cobalt chromium although other materials may be used, such as zirconium oxide, aluminium oxide etc.
• the surface area of the outer surface of the dental support component may be increased by roughening the implant body in several different manners, such as, e.g. by acid-etching, grit blasting, spark- anodization and/or machining.
• the outer surface can comprise macroscopic structures, such as, for example, threads, micro-threads, indentations, and/or grooves that are configured to promote osseointegration and can be used alone or combined with the roughening.
• the outer surface may comprise a microstructure surface, such as, a highly crystalline and phosphate enriched titanium oxide microstructures surface with open pores in the low micrometer range.
• the implant in particular the dental support component, may be made of a zirconium ceramic body that is coated with porous zirconium to provide a microstructure surface. It is also possible to use a dental support component having a surface that is provided with growth factors, preferably transforming growth facors Beta, e.g. bone morphogenetic protein (BMP-2, -4, -7), or in combination with platelet rich plasma (PRP). Growth factors may further include any one selected from the group
• PDGF platelet-derived growth factor
• VEGF vascular endothelial growth factor
• IGF insulin-like growth factor
• FGF fibroblast growth factors
• GDF-5 differentiation factor 5
• Osseointegration is the direct structural and functional connection between living bone and the surface of an implant.
• An intense blood protein coating and an intense fibrin network integration of the implant surface will influence the cascade of cell-interrogation, recruitment, proliferation, differentiation and maturation of matrix.
• Fibrin fibers which form the preliminary matrix are "highways" on which soft tissue and hard tissue forming cells move along to the implant surface. Proteins and growth factors released from activated platelets support and organize cellular
• the platelet-released factors also induce and amplify the migration, proliferation and differentiation of endothelial cells and thereby initiating angiogenesis .
• the invasion and sprouding of blood vessels is a prerequisite for a sufficient nutrition and oxygen supply, demanded by highly active regenerative cells.
• Soft tissue sealing around an implant and, in particular a dental support element such as an abutment is a prerequisite for a long lasting fixation of an inserted implant.
• the dental support element i.e. implant, abutment, crown
• the oral microflora such as bacteria, fungi, viruses.
• Leakage of the soft tissue sealing can induce peri- implantitis which, in the worst case, leads to a loss of the implant .
• the above-defined agent is used for producing a coating on a dental support component.
• the agent is dissolved in water forming an aqueous solution.
• the aqueous solution for producing a coating on the surface of the ceramic or metallic implant is as defined above.
• the method of coating the ceramic or metallic implant with the above-defined agent is not particularly limited and any known method may be employed.
• the ceramic or metallic implant e.g. the dental support component
• the ceramic or metallic implant may be immersed in the aqueous solution, i.e. the above-defined aqueous solution, at ambient temperature (25 °C) for e.g. 10 min.
• a porous dental support component it is recommendable to apply a low vacuum (e.g. 600 mbar) for e.g. about 10 min to ensure that the coating solution penetrates into the pores.
• the implant is removed from the solution and air-dried by e.g. 37°C for 30 min.
• a drying of the coated implant is not essential though.
• the above exemplified method can be suitably modified, if desired.
• Such a pre-treatment is preferred in case of a porous implant because it is beneficial to remove adsorbed water inside the pores before carrying out the coating procedure.
• the so-treated implant is coated with the coating solution by e.g. immersing the implant, e.g. the dental support component, in the coating solution.
• the present invention provides a ceramic or metallic implant that is provided with at least one coating, wherein said coating is obtainable by immersing the ceramic or metallic implant in an aqueous solution comprising trisodium citrate, citric acid, monobasic sodium phosphate, dextrose and adenine.
• aqueous solution comprising trisodium citrate, citric acid, monobasic sodium phosphate, dextrose and adenine.
• the thickness of the coating is not specifically limited and may be between a few micrometers to some millimeters.
• the thickness of the coating depends on the concentration of the coating solution and the coating conditions. In general it can be said that a higher concentrated coating solution increases the thickness of the coating on the implant.
• the surface of the implant coated with the above-defined agent in particular with the above-defined coating solution, comprising trisodium citrate, citric acid, monobasic sodium phosphate, dextrose and adenine, is
• the wettability of the coated implants has been determined by measuring the contact angle according to the Sessile-Drop-Method.
• the water droplet completely spreads on the surface within some seconds, such as below 50 ms, more particular about 5 to 10 ms .
• Such a wetting behavior is typical for hyperhydrophilic surfaces.
• the present invention relates to a kit for use in a method of installing a ceramic or metallic implant, wherein the kit comprises a ceramic or metallic implant, such as a dental support element, trisodium citrate, citric acid, monobasic sodium phosphate, dextrose and adenine .
• a ceramic or metallic implant such as a dental support element, trisodium citrate, citric acid, monobasic sodium phosphate, dextrose and adenine .
• the kit according to the fourth aspect contains trisodium citrate, citric acid, monobasic sodium phosphate, dextrose and adenine as dry agents packaged in the form of dry powders .
• Such dry powders may be packaged separately or as a mixture of two or more or all of the dry agents.
• these dry powders can be dissolved in an appropriate amount of water to prepare the above-defined coating solution.
• the kit contains an aqueous solution containing trisodium citrate, citric acid, monobasic sodium phosphate, dextrose and adenine. It is preferred that the kit contains the aqueous solution according to the above described preferred embodiments.
• the aqueous solution to be contained in the kit of the present invention consists of 2.63 to 5.26 g/1 of trisodium citrate, 0.327 to 0.654 g/1 of citric acid, 0.222 to 0.444 g/1 of monobasic sodium phosphate, 3.19 to 6.38 g/1 of dextrose, and 0.0275 to 0.055 g/1 of adenine, and the rest is water.
• a standard dental implant a bone level implant, produced by the company "Institut Straumann AG”.
• This implant has a sand-blasted and acid etched surface. It has been coated with an aqueous coating solution having the following composition:
• the implant has been immersed in the coating solution for 10 min. Then, low vacuum of 600 mbar has been applied. After 10 min, the implant has been removed from the coating solution and dried at 37°C for 20 min.
• the coated implant For determining the coagulation of blood in direct contact with the implant surface the coated implant has been exposed to fresh (i.e. uncoagulated) human blood.
• the coagulation property serves as an indication of beneficial conditions for enabling osseointegration . Therefore, the coated implant was placed in an Eppendorf vial and the blood was added. After 10 min the implant was removed and fixed in a formaldehyde solution. The so-fixed implant was stored over night at 4 °C.
• a zirconium oxide-type abutment having a rather polished, machined surface has been coated in the same way as described in Example 1.
• the coated abutment has been treated with blood in the same way as described in Example 1.
• Figs. 2a and 2b The surfaces of the blood-treated abutments are shown in Figs. 2a and 2b. It is apparent from the comparison of Fig. 2a with Fig. 2b that the blood protein coating, the platelet activation and fibrin fiber connection is greatly improved on the surface of the implant according to the present invention compared to an untreated implant.
• Example 3
• a zirconium oxide dental implant having a porous and, thus, rather rough surface texture has been coated in the same way as described in Example 1.
• the coated dental implant has been treated with blood in the same way as described in Example 1.
• the non-coated dental implant has been treated with blood in the same way.
• Figs. 3a and 3b The surfaces of the blood-treated dental implants are shown in Figs. 3a and 3b. It is apparent from the comparison of Fig. 3a with Fig. 3b that the blood protein coating, the platelet activation and fibrin fiber connection is greatly improved on the surface of the implant according to the present invention compared to an untreated implant.
• TiUniteTM A titanium dental implant having an oxidized -porous surface sold under the trademark TiUniteTM has been coated in the same way as described in Example 1.
• the coated dental implant has been treated with blood in the same way as described in Example 1. Furthermore , for
• the non-coated dental implant has been treated with blood in the same way.
• Figs. 4a and 4b The surfaces of the blood-treated dental implants are shown in Figs. 4a and 4b. It is apparent from the comparison of Fig. 4a with Fig. 4b that the blood protein coating, the platelet activation and fibrin fiber connection is greatly improved on the surface of the implant according to the present invention compared to an untreated implant.

Landscapes

• Health & Medical Sciences (AREA)
• Oral & Maxillofacial Surgery (AREA)
• Life Sciences & Earth Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Epidemiology (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Transplantation (AREA)
• Dermatology (AREA)
• Dentistry (AREA)
• Engineering & Computer Science (AREA)
• Plastic & Reconstructive Surgery (AREA)
• Inorganic Chemistry (AREA)
• Ceramic Engineering (AREA)
• Orthopedic Medicine & Surgery (AREA)
• Biomedical Technology (AREA)
• Molecular Biology (AREA)
• Dental Preparations (AREA)

Priority Applications (1)

Applications Claiming Priority (2)

Related Child Applications (1)

Publications (1)

Family

ID=46799637

Family Applications (1)

Country Status (2)

Cited By (1)

Citations (5)

Family Cites Families (8)

• 2012
  • 2012-07-14 GB GB1212568.8A patent/GB2503949A/en not_active Withdrawn
• 2013
  • 2013-07-05 WO PCT/EP2013/001981 patent/WO2014012630A1/fr not_active Ceased

Patent Citations (5)

Non-Patent Citations (1)

Also Published As

Similar Documents

Legal Events