WO2011058345A2

WO2011058345A2 - Root canal therapy

Info

Publication number: WO2011058345A2
Application number: PCT/GB2010/051857
Authority: WO
Inventors: Peter Gowers; David Simpkins; Jack Blass
Original assignee: Landmark Innovations Ltd.
Priority date: 2009-11-10
Filing date: 2010-11-09
Publication date: 2011-05-19
Also published as: GB2470088B; GB2470088A; GB0919647D0; WO2011058345A3

Abstract

The present invention provides a shaped filling body (dental point) for filling a dental root canal, wherein the shaped filling body comprises a water-soluble, anti-microbial glass compound. Root canal filler compositions are also provided along with a kit of parts and methods for filling a root canal. Such products may be used to prevent infection of the root canal and to promote recalcification of the tooth.

Description

ROOT CANAL THERAPY

Field of the Invention

This invention relates to the area of dental treatment known as root canal therapy and has improved (properties) benefits (to both the patient and the dentist) over those known in the prior art. More particularly this invention deals with the requirement during the root canal treatment procedure to eliminate the infection processes and ensure the non-recurrence of a requirement for retreatment.

Description of Prior Art

A tooth is anatomically made of four elements; enamel, dentine, cementum and pulp. All the elements are hard structures with varying degrees of hardness and permeability except the pu!p which fills a hollow space within the dentine of the tooth and is made up of the arteries, veins and nerves which keep a healthy tooth alive.

There are several types of clinical treatments carried out in dentistry. The most common treatments are filling a tooth, which comes under the clinical title of "restorative dentistry" and root canal filling, which is falls within the title of "endodontics", and there is a significant difference between the two treatments.

Filling a tooth is required when part of its hard structure (i.e. enamel, dentine or cementum) has been damaged by any one of many causes, the most frequent of which is dental decay (caries) or tooth fracture due to a blow or similar event. The purpose of the filling is to restore the tooth to as near its original shape and function as possible. In order to do this, the dentist has a variety of filling materials to choose from. Based on the location of the defect on the tooth and the forces to which it will be exposed, the dentist can choose either white fillings for aesthetic reasons or gold, silver and even white material with suitable strength. The purpose of the tooth filling is to restore the tooth to its functional shape which is necessary for many reasons such as, chewing, maintaining the teeth in their proper position in the arch and appearance. Such treatments are disclosed in US 2007/0122356 and WO 03/074009. Root canal filling on t e other hand, involves filling the hollow space within the body of the tooth which was occupied by the pulp of the tooth before it became infected. It may be that the tooth has been infected and pain free for some time and has been discovered as a dead tooth on a routine visit to the dentist or as a result of a painful experience. In the event that the root canal infection has migrated through the apical foramen into the surrounding periapical tissue, this may be the cause of bone loss around the apex of the tooth root, and loss of a portion of the root itself, evidence of which will be seen on x-ray. In these circumstances the tooth is generally treated by apicoectomy, as discussed further below. The function of the root canal filling for apicoectomy is to fill a space to stop reinfection reaching the apex. In this respect, the materials used for root filling do not have the same properties of strength, colour and polymerisation and the like, as used in restorative dentistry.

The root canal treatment procedure currently used is to drill through the enamel and dentine of the crown to gain access to the pulp chamber. Using special instruments the infected or damaged pulp is removed. The root canal is then cleaned to remove any remaining debris and disinfected. The filling of prepared root canals has traditionally been accomplished through the use of solid, shaped filling bodies or "points." Thus, tapered cones or "points" of gutta percha or other material of the correct size for the canal to be filled is selected, coated with a cement, and placed in the prepared canal. Frequently antimicrobial dressings are used. This form of treatment can sometimes be done in one appointment but more generally it takes two or more depending on the severity of the infection. The antimicrobial dressings used contain antibiotics or other compounds which are not necessarily effective against all organisms, particularly anaerobic organism which are often implicated, and do not remain in place for an extended period. This process is therefore not only time consuming, since the treatment involves a minimum of two steps but also more proned to reinfection occurring. Moreover, this multi-step process is usually painful and inconvenient to a patient.

In some teeth the roots are curved especially towards the apex and in others the canals are very thin. In both instances it may be impossible to clean to the apex using instrumentation. In such cases an operation called an apicoectomy is undertaken. This is an invasive operation which involves lifting a gum flap, gaining access to the apical area by removal of the overlying bone, removing a few millimetres of the root at the apex and then sealing the tooth at the apex with an appropriate filling material.

A major disadvantage of the current method of root canal treatment is that it does not address the causation of why a proportion of the treatments fail and have to be carried out again, nor does it offer an alternative to the need for an apicoectomy. Reinfection can occur as a result of caries under the filling or the crown done to restore the tooth after a root canal treatment. The bacteria can enter the canal under the crown and pass up the side of the canal between the filling and the inner of the root to reach the apex. The invention therefore focuses on these bacteria being killed by the reservoir of metals or metal- containing compounds comprised in the anti-microbial glass compounds long before they got near the apex.

The presence of voids in the filled canal space is believed to foster the growth of bacteria, hence the incomplete filling of the canal space is to be avoided. However, in the prior art, it is stated to be desirable to control carefully the insertion of root canal filling material and cement to avoid overfilling. Excessive tamping or instrumentation of points can cause extrusion of the cement used therewith and sometimes the points themselves through the apical foramen into the periapical space. Such extrusion is generally believed to be harmful, to cause irritation of the tissues located at the apex, and to retard the healing thereof.

It is an object of this invention to provide a novel method of eliminating the infection processes that require a tooth to be root treated and at the same time to remove the possibilities of the root treatment having to be redone or requiring an apicoectomy. More particularly it is considered that this can be done without going through the procedure of completely cleaning the root canal by instrumentation. This means that the present method does not require filling the root canal with gutta percha as is done in currently accepted methods, since the anti-microbial glass compounds line the inner surface of the canal and remains there to kill all the bacteria. With the present invention, the bacteria would be killed by the metals, such as silver, in the dentine of the root canal. Furthermore, this immediate release of anti-microbial material is supported by the reservoir of anti-microbial material which is leached out of the shaped filling body of the invention. Thus, the invention provides both immediate and controlled release of anti-microbial material which allows the root canal to be filled in a single step. Furthermore, the leaching of the anti-microbial glass allows for remineralisation of the root canal, the apex of the tooth and any bone beyond the apex which has become infected and eroded.

Summary of the Invention

According to a first aspect of the present invention, there is provided a shaped filling body for filling a dental root canal, wherein the shaped filling body comprises a water-soluble, anti-microbial glass compound which comprises one or more metals or metal-containing compounds, wherein the metal is selected from the group consisting of silver, copper, zinc, boron and antimony.

According to a second aspect of the present invention, there is provided a root canal filler composition comprising a water-soluble, anti-microbial, sodium calcium phosphate glass compound which further comprises one or more metals or metal-containing compounds, wherein the metal is selected from the group consisting of silver, copper, zinc, boron and antimony.

According to a third aspect of the present invention, there is provided a kit of parts comprising a shaped filling body for filling a dental root canal, and a dental cement composition, wherein at least one of the shaped filling body or the dental cement composition comprises a water-soluble, anti-microbial glass compound which comprises one or more metals or metal-containing compounds, wherein the metal is selected from the group consisting of silver, copper, zinc, boron and antimony.

According to a fourth aspect of the invention, there is provided the use of a shaped filling body or composition according to any of the previous aspects of the invention, for simultaneously providing anti-microbial activity and promoting recalcification in a dental root canal.

According to a fifth aspect of the present invention, there is provided a shaped filling body for filling a dental root canal, wherein the shaped filling body comprises one or more metals or metal-containing compounds in the form of particles, wherein said particles have an average particle size in the range of 0.1 nm to 500 L m, and wherein the metal is selected from the group consisting of silver, copper, zinc, boron and antimony.

Brief Description of the Drawings

Figure 1 is a representation of tooth anatomy insofar as it is relevant to an understanding of the present invention. Those skilled in the art will recognize that root canal therapy is generally indicated for teeth having sound external structures but having diseased, dead or dying pulp tissues. Accordingly, such teeth will generally possess intact enamel 1 and dentin 2, and be satisfactorily engaged with the bony tissue 6, by, inter alia, healthy periodontal ligaments 5. In such teeth, the pulp tissue 3, and excised portions of the root 4, should be replaced by a biocompatible substitute. Notice should be taken of the apical foramen 7, the orifice through which blood and nerves pass to support the pulp tissues.

Detailed Description of the Invention

Shaped filling bodies

The shaped filling bodies of the present invention are otherwise known as "points" in the dental art. Such shaped filling bodies are solid and may be rigid or flexible. Such shaped filling bodies are preferably manufactured from a polymeric material (e.g., acrylic polymers, polyethylene glycol polymers, synthetic rubbers, etc.), paper, gutta percha or a metal.

The shaped filling body may be made from a single material, or a mixture of materials. In a particularly preferred embodiment, the shaped filling body comprises a polymeric material. The polymeric material is preferably a hydrophilic polymeric material.

In one embodiment of the invention, there is provided a coating composition for the shaped filling body which comprises a hydrophobic polymer and a swellable hydrophilic polymer. In this embodiment, the ratio of the hydrophobic polymer to swellable hydrophilic polymer is in the range of 5:95-95:5, more preferably 40:60-80:20, more preferably 60:40-90:10, based on combined weight of the hydrophobic polymer and swellable hydrophilic polymer. As used herein, the term "hydrophilic" is characterized by the fact that water will spread on the surface. A hydrophilic material is a material upon which water will form a contact angle of less than 45°, preferably less than 20°. The above mentioned contact angle is measured at 30 seconds after wetting and at 25°C, and is carried out on a flat, smooth, horizontal surface of the material.

By contrast, "hydrophobic" means surfaces on which water will form separated drops having a contact angle of greater than 75°, preferably greater than 80°, more preferably greater than 90°, for example, greater than 100°, 110°, 120°, 130°, 140° or 150°. In short, hydrophobic materials are non-wettable or poorly wettable. The above mentioned contact angle is measured at 30 seconds after wetting and at 25°C, and is carried out on a flat, smooth, horizontal surface of the material.

Preferably, the shaped filling body has dimensions selected to fit the size of the cavity in the root canal. The shaped filling body including the coating, where present, can be approximately circular in section and extended cone- shaped, tapering along its length to a point. By "approximately circular", it is meant that, at any point along its length, the ratio of the greatest diameter of the shaped filling body to the smallest diameter thereof is in the range of 1.5:1-1 :1 , preferably 1.4:1-1.05:1 , preferably 1.3:1 -1.1 :1 , for example 1.2:1 -1.1 :1. It is normally presented in a greater length than the root canal into which it is placed and cut to length when inserted. As the shaped filling body is normally swellable, shorter length bodies may be used so as to fit within the length of the canal and do not require to be cut to fit. The shaped filling body may be blunt- ended so that it will not project through the apical foramen due it contacting the sides of the canal before it projects through the foramen. In an alternative embodiment, the cross-section of the shaped filling body may be square or rectangular, since once swollen it will fill the root canal space. For similar reasons a parallel sided shaped filling body may also be used.

The generally preferred range of dimensional sizes of shaped filling bodies are as follows: Length = 10-35mm; Tip diameter (or diagonal if not circular) = 0.05-1.6mm; Crown end diameter (or diagonal) = 0.25-2.5mm; Taper = 0-15%. The shaped filling body preferably comprises a material selected from the group consisting of polyolefinic polymers, polyurethane polymers, acrylic polymers, acrylamide polymers, amide polymers, mixtures thereof, and copolymers thereof.

Preferred polymers include homo- and co-polymers selected from the group consisting of polyethylene glycol, polylactic acid, polyethyleneoxide/cross-linked urethane, polybutyrene succinate, cellulose ethers, polyacrylamides, and maleic anhydride polymers, and mixtures thereof.

In a preferred embodiment, the shaped filling bodies of the present invention are swellable. This may be effected by making the entire shaped filling body from a swellable material or coating a shaped filling body with one or more swellable materials. Preferably, this is achieved by including at least one hydrophilic polymer in the shaped filling body or in a coating thereon.

Preferably, at least a portion of the shaped filling body is coated with a polymeric material, preferably a swellable hydrophilic polymer. Preferably 10- 100% of the surface of the shaped filling body is coated with such a polymer, for example 25-100%, preferably greater than 50%, preferably greater than 75%.

Particularly preferred shaped filling body materials include hydrophilic polyurethane polymers having free hydroxyl and free carboxyl groups in the polymer backbone obtained by hydrolysis of polyurethane polymers having lactone groups in the polymer backbone. Preferred hydrophilic polyurethane polymers are soluble in aqueous solutions, preferably alkaline solutions.

Such polymers can provide a leachable substrate where the leaching agent is the water-soluble, anti-microbial glass referred to above. Such a polymer preferably provides a hydrophilic polyurethane resin having free hydroxyl groups and free carboxylate groups in the polymer backbone obtained by hydrolysis of a polyurethane resin having lactone groups in the polymer backbone.

In a preferred embodiment, the polyurethane resin having lactone groups in the polymer backbone is the reaction product of: (1) one or more diols selected from (a) diethylene glycol, (b) long chain polyoxyalkylene diols having a molecular weight of at least 200, (c) linear polyester diols derived from the condensation of one or more diols with one or more dibasic acids, and (d) the reaction product of one or more alkylene diols or polyoxyalkylene diols with a difunctional linear polyester derived from the condensation of one or more diols with one or more dibasic acids; (2) a polyfunctional lactone having the formula:

wherein R is -H, -CH₂NH₂, -S0₂CH₃, -CHOHCOOH, or -(CHOH)_nCH₂OH; n is 0 or an integer from 1 to 5; and R₂ is a divalent radical -(CHOH)_m-; m being an integer from 2 to 10; and ethers derived from said lactones, and (3) a urethane precursor selected from organic polyisocyanates and nitrile carbonates.

The polyurethane resins according used in the invention can be obtained by hydrolysis of polyether urethane resins having active and available lactone groups in the polymer backbone that readily open and dissolve in alkaline solutions to produce carboxylates which can be converted to free carboxyl groups. Typically they are low-melting, solids, generally having flow points in the range of 90°C to 250°C which can be fabricated by conventional polymer procedures.

GB 1 ,605,079 also discloses suitable polymeric materials for use in the present invention.

In a preferred embodiment, the shaped filling body contains at least one type of water-soluble, anti-microbial glass, as defined herein. In this embodiment, the glass material may be leached or dissolved out of the shaped filling body once the shaped filling body is in situ, i.e., when placed in the dental root canal. This is capable of providing a two-fold benefit. Firstly, this provides an amount of anti-microbial material which sterilises the root canal and/or provides a reservoir of anti-microbial material which prevents any further infection of the root canal. Secondly, the glass material is capable of providing a reservoir of material which contains material which causes recalcification of the root canal, preferably of the area surrounding the apical foramen. This can, eventually, lead to closure of the apical foramen, thereby sealing the root canal against any further infection. Furthermore, should material pass through the apical foramen, it will remove any source of infection in this area and be absorbed.

Such shaped bodies may be inserted into prepared root canals and allowed to swell through absorption of aqueous media. This preferably leads to a substantially complete filling of the canal space. Such swelling also accomplishes the substantial filling of naturally and artificially created lateral spaces, thus to promote the benefits resulting from such substantially complete filling.

Another object of the present invention is to eliminate all the remaining infection sources. This may be effected by using a swellable shaped filling body in conjunction with an anti-microbial compound. It is desired that the swellable polymer should be non-toxic and can be non-biodegradable or biodegradable. It is also desired that the antimicrobial compounds should have a range of solubility from rapidly soluble to nearly insoluble and that they should be non-toxic if deposited or implanted within living human tissues. In particular, some rapidly soluble antimicrobial components are known to kill all bacteria involved in root canal infection within minutes. The nearly insoluble antimicrobial components will act as a depot for maintaining sterility (thereby preventing re-infection) in and around the root.

Where the shaped filling body is coated with a hydrophilic polymeric coating (which is a different material from the rest of the shaped filling body material), preferably it is coated with a substantially uniform coating thereof, in an amount of from 5-85% by weight, preferably 10-75%, for example 20-50% by weight of the final shaped filling body. By "uniform" it is meant that the maximum coating thickness is no greater than 30% thicker than the minimum coating thickness, preferably no greater than 20% thicker, more preferably no greater than 10% thicker.

Glasses may be incorporated with solubilities ranging from greater than zero to 25mg per hour at 38°C. Preferably, the dissolution rate is within the range 0.0001-10000 micrograms per hour at 38°C. Preferably, it is advantageous to use both a slow dissolving glass in the range 0.001-0.1 micrograms per hour at 38°C, and a more rapidly dissolving glass in the range 500-1000 micrograms per hour at 38 'C, so as to obtain a rapid kill of microorganisms and a depot effect.

The anti-microbial glass is preferably incorporated in the shaped filling body in an amount of 0.01 % to 10%, preferably 0.02 to 5%, preferably 0.05 to 3%, preferably 0.1 to 2% by weight based on the weight of the shaped filling body.

Where the shaped filling body comprises polymeric coating, for example, a hydrophilic coating, the anti-microbial glass is preferably incorporated in the coating in an amount of 0.01% to 10%, preferably 0.02 to 5%, preferably 0,05 to 3%, preferably 0.1 to 2% by weight based on the weight of the coating.

The anti-microbial glass may be incorporated in variable loadings in the shaped filling body and/or its coating. For example, a high proportion of the anti-microbial glass may be incorporated closer to the surface of the shaped filling body (or its coating) whereas a smaller proportion may be incorporated further away from the surface of the shaped filling body (or its coating). This would allow for an initially high leaching rate, and a low, but sustained release of the anti-microbial glass. Other loadings which provide different anti-microbial material release rates will be evident to the skilled person.

The anti-microbial glass may be incorporated into the shaped filling body by incorporating it in the manufacture thereof, for example, by mixing prior to forming of the shaped filling body.

Where the shaped filling body comprises polymeric coating or surface, for example, a hydrophilic coating, the anti-microbial glass is preferably incorporated in the coating by loading the coating with the anti-microbial glass. This can be effected by making a solution and/or a suspension ("treatment solution/suspension") of the anti-microbial glass and treating the coating with the solution/suspension or including the solution or suspension in the material used to coat the shaped filling body. The coating may then be dried to retain the anti-microbial glass in the coating.

The time the coating or shaped filling body is treated with the treatment solution/suspension containing the anti-microbial glass may be used to variably load the shaped filling body with anti-microbial glass. Thus, the longer the coating or shaped filling body is treated with the solution/suspension, the greater the loading concentrations are that can be achieved. The treatment solution/suspension may comprise water and/or an organic solvent. In this embodiment of the invention, it is preferred to apply the treatment solution/suspension to a shaped filling body having a substantially dry surface/coating (i.e., containing water levels of less than 10%, preferably less than 5% by weight of any material capable of absorbing water). In this way, the treatment solution/suspension may be used to swell the coating/surface of the shaped filling body, thereby ensuring good penetration thereof, hence the anti- microbial glass, into the polymeric coating/surface of the shaped filling body.

A treatment solution/suspension preferably contains the water-soluble, anti-microbial glass compound in an amount from 2-75 % by weight of the solution/ suspension, preferably 5-50 %, for example, 10-40% or 20-30% by weight of the solution/suspension. It may be possible to achieve higher loadings of the water-soluble, anti-microbial glass compound if more concentrated treatment solution/suspensions are used.

Alternatively or additionally, the coating of the shaped filling body or the shaped filling body itself may be made from a composition which incorporates the anti-microbial glass. This may be effected by polymerising a composition comprising the materials used to produce the coating of the shaped filling body or the shaped filling body itself, and a solution or suspension of the water soluble glass.

Where the shaped filling body comprises a coating of a polymeric material, the coating is preferably in the range of 1-750 μηη thick on average, preferably from 5-250 Mm thick on average, for example 10-200 μιη, 25-150 μιη or 50-100 Mm thick on average.

The shaped filling body may be coated by conventional coating techniques such as immersion, spray coating and the like. The coating composition may be polymerised prior to coating or after coating.

The shaped filling body may be made using conventional techniques.

For example, where the shaped filling body is made from a polymeric material, it may be injection moulded, cast or machined. The shaped filling body of the present invention may comprise any of the component parts of a recalcification-promoting composition. For example, the shaped filling body may comprise one or more elements and/or compounds including sodium, calcium, phosphorus, oxygen, phosphate and hydroxyapatite (i.e., Ca₅(P0 )₃(OH)).

According to a further aspect of the present invention, there is provided a shaped filling body for filling a dental root canal, wherein the shaped filling body comprises one or more metals or metal-containing compounds in the form of particles, wherein said particles have an average particle size in the range of 0.1 nm to 500 urn, and wherein the metal is selected from the group consisting of silver, copper, zinc, boron and antimony.

According to this aspect of the invention, the shaped filling body is preferably made from a polymeric material which comprises between 0.1 -10% by weight of the metal or metal-containing compound, preferably 0.25-5% by weight, preferably 0.5-2.5% % by weight of the metal or metal-containing compound.

In this aspect of the invention, preferably the particles are of a native metal having the average particle size is in the range of 0.1 -1000nm, preferably 1 -200nm. Alternatively, In this aspect of the invention, preferably the particles are of a metal compound having the average particle size is in the range of 0.1 -

Where the particles are of a soluble metal compound, the particles preferably have the average particle size is in the range of 1 nm-100 μιη.

In this aspect of the present invention, the metal or metal compound is preferably selected from colloidal silver, silver oxide and silver benzoate.

According to this aspect of the invention, the shaped filling body may be impregnated with a particulate metal or metal compound. Alternatively, the metal or metal compound may be precipitated as particles during the production of the shaped filling body.

Root Canal Filler Composition According to the second aspect of the present invention, there is provided a root canal filler composition comprising a water-soluble, antimicrobial, sodium calcium phosphate glass compound which, in addition to the sodium and calcium metals in the glass, comprises one or more metals or metal-containing compounds, wherein the metal is selected from the group consisting of silver, copper, zinc, boron and antimony.

The root canal filler composition may be a solid or a liquid composition. For example, prior to application to the root canal, the composition may be presented as a solid material, such as a powder, which requires solubilising and/or suspending prior to application to the root canal. In this respect, a root canal filler powder composition may be mixed with a solvent in a predetermined amount in order to produce a suitable fluid material which may be readily applied to the root canal. Such solvents are preferably selected from alcohols (such as ethanol or propanol) and water and a mixture thereof.

Alternatively or in addition to a solid root canal filler composition, the present invention includes fluid root canal filler compositions. Such fluids may comprise a neat liquid root canal filler material, or may comprise a suspension and/or solution of a solid root canal filler composition. For example, a fluid root canal filler composition may comprise or consist of the solid root canal filler composition as described above, but with the addition of a solvent, such as water.

The root canal filler composition preferably comprises a cement selected from the group consisting of a zinc phosphate cement, a carboxylate cement, an ionomer cement, and a resin cement, and mixtures thereof. Any such cement material is preferably present in the root canal filler composition of the invention in an amount of from 0-90%, for example, 1-70%, 5-50% or 10-25%, by weight of the root canal filler composition.

Preferably, the canal filler composition comprises an aqueous, poly(carboxylic acid) cement (otherwise known as a carboxylate cement). Such compositions preferably comprise (i) a polymer containing free carboxylic acid groups (typically a homo-or co-polymer of acrylic acid) and (ii) an ion-leachable glass. The canal filler composition preferably comprises a cement powder which will react with the poly(carboxylic acid) in the presence of water to give a plastic mass which rapidly hardens to form a poly(carboxylate) cement.

In the presence of water, the glass leaches metal ions selected from the group consisting of silver, copper, zinc, boron and antimony. Such glasses may also leach ions including one or more ions including sodium, calcium, phosphate and hydroxyapatite. The leaching of the former (i.e., silver, copper, zinc, boron and antimony) contributes to the anti-microbial activity of the glass. The leaching of the latter (i.e., the recited ions) contributes to recalcification of the root canal.

The rate of leaching of the metal or metal compound (silver, copper, zinc, boron or antimony) from a root canal filler composition is preferably in the range of 1 -1000 nanograms of metal or metal compound, per 24 hours, preferably 10-7500, more preferably 30-500, for example 50-400 or 100-250 nanograms of metal or metal compound, per 24 hours.

The root canal filler composition preferably contains the water-soluble, anti-microbial glass in the composition in an amount of 0.01 % to 10%, preferably 0.02 to 5%, preferably 0.05 to 3%, preferably 0.1 to 2% by weight based on the weight of the root canal filler composition.

When the root canal filler composition is mixed with a solvent in order to make is applicable to the root canal, the composition is thoroughly mixed in order to achieve a homogeneous mix of the water-soluble, anti-microbial glass throughout the mixture, but also to ensure that, if any hydrophilic swellable polymers are present, that they are also homogeneously mixed. The mixing of the latter will help to achieve an even swelling of the material in situ. Such mixing may be effected by hand or by using a mechanical mixer.

The water soluble poly (carboxy lie acid) preferably has a relative viscosity as hereinafter defined of from 1.05 to 2.0. This relative viscosity range generally corresponds to an average molecular weight of from 1500 to 150,000 when determined by the method of Sakamoto (Chemical Abstract 58 13160c). In this specification relative viscosity is defined as the viscosity measured with a capillary viscometer of a 1 % by weight to volume solution of the poly(carboxylic acid) in twice molar sodium hydroxide solution at 25°C relative to the viscosity of the twice molar sodium hydroxide solution. The preferred po!y(carboxylic acids) are those prepared by the homo- polymerisation and co-polymerisation of unsaturated aliphatic carboxylic acids, for example acrylic acid, 2-chloroacrylic acid, 3-chloroacrylic acid, 2- bromoacrylic acid, 3-bromoacrylic acid, methacrylic acid, itaconic acid, maleic acid, glutaconic acid, aconitic acid, citraconic acid, mesaconic acid, fumaric acid and tiglicinic acid. Suitable monomers for co-polymerising with the unsaturated aliphatic carboxylic acids include unsaturated aliphatic compounds such as for example acrylamide, acrylonitrile, vinyl chloride, allyl chloride, vinyl acetate, and 2-hydroxyethyl methacrylate. Ter- and higher polymers may be used if desired.

Poly(carboxylate) cement kits in accordance with this invention preferably comprise a poly(carboxylic acid) in the form of an aqueous solution containing from 20 to 65% by weight of the polyfcarboxylic acid). The poly(carboxylate) cement pack may be a two part kit pack in which the weight ratio of powder to liquid in the two parts is preferably from 0.5:1 to 5:1 so that when the entire contents of the kit are mixed together a rapidly hardening cement is obtained. In another embodiment the kit may contain the powder and the liquid in separate capsules, the total amount of powder in the pack and the total amount of liquid in the pack being in the appropriate ratio. In a further embodiment, both components may be encapsulated in the same capsule, in the desired ratio, provided that steps are taken to prevent premature reaction. In a still further embodiment the pack may be a one part pack containing an intimately blended mixture of the cement powder, solid water-soluble poly (carboxylic acid), the ratio of powder to poly (carboxylic acid) preferably being from 1 :1 to 10:1 , the mixture requiring the addition of water to produce the cement. The mixed powder and the water may be contained in the same capsules provided steps are taken to prevent premature reaction, for example by dividing the capsule. This latter procedure generally requires some form of mechanical mixing.

In the above mentioned embodiments the cement powder is preferably from 15 to 85% by weight, the poly(carboxylic acid) is from 3 to 50% by weight, and the water is from 5 to 70% by weight of the total composition. The cement powder may, preferably, comprise a simple metal oxide, preferably one that has been de-activated by heat treatment, for example zinc oxide to which there may be added up to about 10% by weight of other metal oxides such as for example magnesium oxide. Alternatively, the cement powder may comprise a fused oxide, made by heating a mixture of simple oxides to fusion temperature, or an oxide glass, for example one comprising calcium or sodium oxide with alumina, silica and phosphorus pentoxide.

The root canal filler composition of the invention may further contain a water-soluble or water-swellable polymer or copolymer. Preferably, the water- soluble or water-swellable polymer is selected form the group of polyacrylic acid, polyvinylalcohol, polyvinylamine, polyvinylpyrolidone. Preferably, the water-soluble copolymer is obtained by polymerization of at least two different polymerizing monomers in that manner that at least one of the polymerizing monomers contains acidic moieties selected of the group of carboxylic acids, phosphoric acid, phosphonic acid, sulfuric acid, sulfonic acid. In a preferred embodiment, the water-soluble copolymer is obtainable by polymerization of at least two different polymerizing monomers selected of the groups (a) monomers such ethylene, propylene, styrene, methylmethacrylate, methylacrylate, butylmethacrylate, vinylalkylether and (b) acidic monomers such as acrylic acid, methacrylic acid, vinylphosphonic acid, maleic acid, fumaric acid, maleic acid anhydride. The water-soluble or water-swellable polymer or copolymer may be present in the root canal filler composition of the invention in an amount of from 0-70%, for example, 1 -50%, 5-30% or 10-25%, by weight of the root canal filler composition.

The dental composition of the invention may further contain additional inorganic fillers widely used for dental composite resins in combination with the reactive inorganic filler. The additional filler preferably has a mean particle size of 0.02 to 10 μιτι and is incapable of reacting with particles with grafted polyacidic polymer chains by a cement reaction. Examples of the additional filler are colloidal silica, quartz, feldspar, alumina, titania, borosilicate glass, kaolin, talc, calcium carbonate, calcium phosphate, and barium sulfate. Composite fillers obtained by pulverizing inorganic filler-containing polymers may be used as well. These fillers may also be used in admixture. Such fillers may be present in an amount of from 0-90%, for example, 1 -70%, 5-50% or 10- 25%, by weight of the root canal filler composition.

If desired, the root canal filler composition of the invention can contain adjuvants such as pigments, non-vitreous fillers, inhibitors, accelerators, viscosity modifiers, x-ray opaque materials, surfactants, and other ingredients that will be apparent to those skilled in the art.

Root canal filler compositions containing such cements and/or fillers should preferably meet such other desirable criteria as: (a) translucency; (b) long shelf life; (c) strong adhesion to the tooth; (d) suitable working and setting times; (e) adequate strength; and (f) containing an x-ray opaque material.

Such canal filler compositions of the present invention are preferably formulated so as to be capable of injection into the lateral spaces of a prepared root canal through the hydraulic compression thereof by an expanding hydrophilic shaped filling body or conventional point.

When satisfactory access to the pulp chamber is achieved, it may be necessary if the pulp is not entirely dead to remove the remains with an instrument before placing the polymer with its antimicrobial content into the root canal. If the pulp is totally dead then the polymer with its antimicrobial content can be placed immediately.

An objective of the present invention is to get the anti-microbial material

(whether it be in the shaped filling body or the root canal filling composition) in contact with the inner surface of root canal. In order to achieve this, it may be necessary to modify the viscosity of the root canal filler composition.

The viscosity of the root canal filler compositions are (when measured within one minute of mixing, at a temperature of 25°C) of between 0.5 poise and 3000 poise. More viscous solutions can only be worked with difficulty and are difficult to apply to the substantially the whole of inner surface of the root canal. The viscosity at 25°C preferably is between 1 and 600 poise, more preferably from 2 to 200 poise, especially from 5 to 100 poise. The root canal filler may comprise a thixotropic material having a viscosity of greater than about 300 poise. The root canal filler composition of the present invention may comprise any of the component parts of a recalcification-promoting composition. For example, the root canal filler composition may comprise one or more elements and/or compounds including sodium, calcium, phosphorus, oxygen, phosphate and hydroxyapatite (i.e., Ca₅(P0₄)₃(OH)).

Kit of Parts of the Present Invention

According to a third aspect of the present invention, there is provided a kit of parts comprising a shaped filling body for filling a dental root canal, and a dental cement composition, wherein at least one of the shaped filling body or the dental cement composition comprises a water-soluble, anti-microbial glass compound which comprises one or more metals or metal-containing compounds, wherein the metal is selected from the group consisting of silver, copper, zinc, boron and antimony. Preferably, the shaped filling body comprises the water-soluble, anti-microbial glass compound. However, in a preferred embodiment, both the shaped filling body and the dental cement composition comprise a water-soluble, anti-microbial glass compound.

In this aspect of the present invention, either or both of shaped filling body and the dental cement composition comprises a water-soluble, antimicrobial glass compound. Where only one of the shaped filling body and the dental cement composition comprises a water-soluble, anti-microbial glass compound, the one which does not include the water-soluble, anti-microbial glass compound may be a conventional shaped filling body or conventional root canal filler composition.

In this aspect of the invention, the component of the kit which includes water-soluble, anti-microbial glass compound (the shaped filling body and/or the dental cement composition), it may have all of the features as recited herein in respect of the shaped filling body or the dental cement composition according to the first and second aspect of the present invention respectively.

The Anti-Microbial Agent

The preferred anti-microbial agents are the metal-containing glasses, most preferably silver containing glasses. Suitable silver and other metal containing glasses are disclosed in European patents EP0379507, EP 0809506, EP1094992, EP1087914 and US 6,143,318 and are preferably sodium calcium phosphate glasses containing the respective metal, prepared by a pyrotechnic method. Other suitable metal-containing glasses are disclosed in US 6,482,444 and are bioactive calcium phosphate silicate glasses containing the respective metal, prepared by a sol-gel method.

According to a particularly preferred embodiment of the present invention, the anti-microbial agent is a water-soluble, silver-containing glass material. Typically the soluble glasses used in this invention comprise phosphorus pentoxide (P₂0₅) as the principal glass-former, together with any one or more glass-modifying non-toxic materials such as sodium oxide (Na₂0), potassium oxide (K₂0), magnesium oxide ( gO) and calcium oxide (CaO). The rate at which the silver-release glass dissolves in fluids is determined by the glass composition, generally by the ratio of glass-modifier to glass-former and by the relative proportions of the glass-modifiers in the glass. By suitable adjustment of the glass composition, the dissolution rates in water at 38°C ranging from substantially zero to 25 mg/cm²/hour or more can be produced. The water-soluble glass is preferably a phosphate glass, and the silver may advantageously be introduced during manufacture as silver orthophosphate (Ag₃P0₄). The content of silver and other constituents in the glass can vary in accordance with conditions of use and desired rates of release, the content of silver generally being up to 10% by weight.

The silver may be in the form of native (metallic) silver, or in the form of one or more silver compounds.

An exemplary water-soluble glass composition contains:

P₂0₅: 30 to 60 mole %;

Na₂0: 30 to 60 mole %; and

K₂0: 5 to 15 mole %;

Ag₂0₃: 0 to 5 mole %;

and optionally may contain:

B₂0₃: 0 to 15 mole %; and/or

NaF: 0 to 5 mole %; and/or

Si0₂: 0 to 5 mole %; and/or

total alkaline earth metal compounds: 0 to 5 mole %. A highly preferred water-soluble glass composition contains:

P₂O_s: 40 to 60 mole %;

B₂0₃: 0 to 10 mole %;

Na₂0: 30 to 40 mole %;

K₂0: 5 to 10 mole %;

Ag₂0; 0 to 5 mole %;

Si0₂: 0 to 5 mole %; and

up to 5 mole % of other additive compounds such as CaO, MgO and ZnO.

Other compounds may also be added to the glass to modify its properties, for example Si0₂, Al₂0₃, S0₃, MgO, CaO, ZnO, sulphate ions or transition metal compounds (e.g. first row transition metal compounds), but these will preferably be present in low quantities, for example up to a total amount of 5 mole % or less of the glass composition.

Preferably Si0₂ is added to the glass compositions in up to 5 mole % based on the weight of the glass composition.

Particularly preferred glasses used as the anti-microbial material in all aspects of the present invention are sodium calcium phosphate glasses. Particularly preferred glasses have the CAS references 7440-50-8, 7440-66-6, 7440-22-4. These materials have the brand names Corglaes copper, Corglaes zinc and Corglaes silver respectively.

The most preferred anti-microbial glass is a silver-containing sodium calcium phosphate glass.

The anti-microbial glass may be incorporated in the compositions of the present invention in an amount of 0.01 % to 10%, preferably 0.02 to 5%, preferably 0.05 to 3%, preferably 0.1 to 2% by weight based on the weight of the final product, as used by the dental practitioner.

In the aspects of the present invention, it is highly advantageous to have a reservoir of anti-microbial material present in the root canal. This advantage is further improved by providing a reservoir of materials which are capable of recalcifying the root canal, particularly the apical foramen, using the same reservoir of material (the anti-microbial glass). This allows immediate and ongoing anti-microbial activity to be achieved in the canal, while simultaneously providing the materials with which the root canal may be rebuilt/closed to further infection. The presence of the glass also provides for the possibility that any damaged bone tissue beyond the apical foramen may be repaired using the leached glass components.

Methods of Application

There are several ways in which the water-soluble, anti-microbial glass may be introduced to the root canal. These include:

1 . Insert one or more shaped filling bodies (as described herein) coated with or made substantially from a swellable polymer containing the antimicrobial material. The shaped filling body can be wetted before insertion or after insertion especially if it is water absorbent. The shaped filling body can be left in situ.

2. Insert a root canal filling composition (as described herein) as a paste or liquid and spin it up the root canal using a rotary filler, either hand operated or by dental handpiece.

3. A combination of 1 and 2 immediately above. Insert a root canal filling composition in the canal and then place one or more shaped filling body inside the canal.

4. If the root canal is curved or very narrow then delivering a suspension of the root canal filling composition in water from a syringe type device as far up the canal as possible will allow it to flow by capillary and by absorption by the dentine to reach the apex. This may be followed by the application of methods 1. and/or 2. immediately above.

When the hydrophilic polymer has expanded to coat all the surface of the root canal the canal will be disinfected. If there is periapical infection, with or without bone destruction, then over-filling the root canal so that polymer is extruded though the apex may be desirable. As the polymer and the antimicrobial compound in this instance are both non-toxic and resorbable, this will assist in the healing process and reduce or eliminate the requirement for an apicoectomy. The root canal filling composition and/or shaped filling body may also contain substances which are known to promote bone regrowth and which may seal the root at the apex.

The crown end of the root canal should be sealed and filled using products well known in the art.

As used herein, the term "for filling a dental root canal" does not necessitate that the root canal is wholly filled, but merely that the body or composition referred to is capable of filling the root canal in the manner and to the extent to which the term is commonly used in the art.

Other components

The compositions of the invention can contain a wide variety of adjuvants depending upon the desired end use. Suitable adjuvants include solvents, diluents, plasticizers, pigments, dyes, inorganic or organic fibrous or particulate reinforcing or extending fillers, thixotropic agents, indicators, inhibitors, stabilizers, UV absorbers, leachable fluorides and the like.

General

The term "comprising" encompasses "including" as well as "consisting" e.g. a composition "comprising" X may consist exclusively of X or may include something additional e.g. X + Y.

The term "about" in relation to a numerical value x means, for example, x+10%.

The word "substantially" does not exclude "completely" e.g. a composition which is "substantially free" from Y may be completely free from Y. Where necessary, the word "substantially" may be omitted from the definition of the invention.

Examples

1 . Shaped filling bodies (points) were made by injection moulding a thermoplastic elastomeric (TPE) polymer (a styrene block copolymer, known as ediprene^®, made by the VTCTPE group) which contained 5% of a silver glass and a hydrophilic acrylic polymer. These were placed on tryptone soy agar plates seeded with Streptococcus mutans and incubated for 24 hours at 35°C. A zone of inhibition of growth of the organism of approximately 0.5-1.0mm was observed.

2. Points (shaped filling bodies) were made by injection moulding a thermoplastic elastomeric polymer containing 5% of a silver glass. This was further coated with a hydrophilic acrylic polymer solution containing 5% of the solids content of silver glass and dried. These were microbioiogically tested as in example 1. A zone of inhibition of 2-5mm around the device was observed.

3. Paper points were coated with an acrylic polymer as in example 2 containing 5% of the solids content of silver glass and tested microbioiogically against S. aureus, Ps. aeruginosa, C. albicans and an oral mixed culture from a volunteer. Zones of inhibition were observed in every case.

4. Coated paper points were prepared and tested as in example 3 against the anaerobic organisms Peptostreptococcus anaerobius and Lactobacillus species using appropriate media. Significant zones of inhibition were observed. It should be noted that, in example 1 , the Streptococcus mutans is a facultative anaerobe.

Claims

1 , A shaped filling body for filling a dental root canal, wherein the shaped filling body comprises a water-soluble, anti-microbial glass compound which comprises one or more metals or metal-containing compounds, wherein the metal is selected from the group consisting of silver, copper, zinc, boron and antimony.

2. The shaped filling body of claim 1 , wherein the shaped filling body comprises a polymeric material, paper, gutta percha, a metal or a mixture thereof.

3. The shaped filling body of claim 2, wherein the polymeric material is a swellable hydrophilic polymeric material.

4. The shaped filling body of claim 2 or claim 3, wherein the polymeric material is selected from the group consisting of polyolefinic polymers, polyurethane polymers, acrylic polymers, acrylamide polymers, amide polymers, polyethylene glycol polymers, polylactic acid, mixtures thereof, and copolymers thereof.

5. The shaped filling body of any of claims 2-4, wherein the polymeric material is coated on the surface of the shaped filling body.

6. The shaped filling body of any preceding claim, wherein the coating or the shaped filling body itself contains the water-swellable, anti-microbial glass compound in an amount of 0.01% to 10%, preferably 0.02 to 5%, preferably 0.05 to 3%, preferably 0.1 to 2% by weight based on the weight of the coating or the shaped filling body.

7. The shaped filling body of any preceding claim, wherein the shaped filling body comprises a coating of a polymeric material, the coating having an average thickness of 1 -750 m thick, preferably from 5-250 m thick, for example 10-200 pm, 25- 50 μηη or 50-100 μιτι thick.

8. The shaped filling body of any preceding claim, wherein the glass comprises a sodium calcium phosphate glass.

9. The shaped filling body of any preceding claim, wherein the glass comprises a silver-containing, sodium calcium phosphate glass.

10. A root canal filler composition comprising a water-soluble, anti-microbial, sodium calcium phosphate glass compound which comprises one or more metals or metal-containing compounds, wherein the metal is selected from the group consisting of silver, copper, zinc, boron and antimony.

11. The root canal filler composition according to claim 10, further comprising a water-swellable polymer or copolymer.

12. The root canal filler composition according to claim 10 or claim 11 , further comprising a cement selected from the group consisting of zinc phosphate cement, carboxylate cement, ionomer cement, resin cement, and mixtures thereof.

13. The root canal filler composition according to claim 10 or claim 11 , further comprising an aqueous, poly(carboxylic acid) cement.

14. The root canal filler composition according to any of claims 10-13, wherein the root canal filler composition preferably contains the water-soluble, anti-microbial, sodium calcium phosphate glass in the composition in an amount of 0.01% to 10%, preferably 0.02 to 5%, preferably 0.05 to 3%, preferably 0.1 to 2% by weight based on the weight of the composition.

15. The root canal filler composition according to any of claims 10-14, wherein the viscosity of the root canal filler compositions are between 0.5 poise and 3000 poise, preferably 1 to 600 poise, more preferably from 2 to 200 poise, especially from 5 to 100 poise.

16. The root canal filler composition according to any of claims 10-15, wherein the glass comprises a silver-containing, sodium calcium phosphate glass.

17. A kit of parts comprising a shaped filling body for filling a dental root canal, and a dental cement composition, wherein at least one of the shaped filling body or the dental cement composition comprises a water-soluble, antimicrobial glass compound which comprises one or more metals or metal- containing compounds, wherein the metal is selected from the group consisting of silver, copper, zinc, boron and antimony.

18. The kit of parts according to claim 17, further comprising any of the features of claims 1 -16.

19. A shaped filling body for filling a dental root canal, wherein the shaped filling body comprises one or more metals or metal-containing compounds in the form of particles, wherein said particles have an average particle size in the range of 0.1 nm to 500 urn, and wherein the metal is selected from the group consisting of silver, copper, zinc, boron and antimony.

20. A shaped filling body according to claim 19, wherein the particles are of a native metal having the average particle size is in the range of 0.1-1000nm, preferably 1-200nm.

21. A shaped filling body according to claim 19, wherein the particles are of a metal compound having the average particle size is in the range of 0.1-100 μπι.

22. A shaped filling body according to claim 19, wherein the particles are of a soluble metal compound having the average particle size is in the range of 1 nm-100 μιτι.

23. The shaped filling body according to claim 19, wherein the metal or metal compound is selected from colloidal silver, silver oxide and silver benzoate.

24. Use of a shaped filling body or composition according to any of claims 1- 23, for simultaneously providing anti-microbial activity and promoting recalcification in a dental root canal.

25. A method of root canal treatment, comprising the step of filling the root canal with a shaped filling body or root canal filler composition according to any of claims 1 -16 and 19-23.