Patent Description:
People with missing teeth use dentures to aid in chewing, improve their appearance, and enhance their speaking ability. Full dentures are used when all teeth are missing, and partial dentures are used when some teeth remain. While it is generally necessary for full dentures to be rigid, partial dentures can be either rigid or flexible, and flexible partial dentures have become more popular because they may flex around the remaining teeth and do not always require invasive procedures. In addition, flexible partial dentures can in some cases be provided to a patient on a same-day basis.

With the demand for flexible partial dentures increasing, there is a need for new approaches to for the prompt manufacture of such dentures in a cost-effective manner.

For example document <CIT> discloses a method of additive manufacturing mouth guards, occlusal splints or denture bases. In some cases a post-curing step by light irradiation or by heat is performed.

Provided herein is a method of making a flexible partial denture, which may include: (a) producing a partial denture base by additive manufacturing (e.g., bottom-up or top-down stereolithography) from a dual cure resin, with the dual cure resin comprising a light polymerizable component and a heat polymerizable component, with the denture base including at least one tooth socket comprising the dual cure resin in uncured or partially cured form; (b) inserting an acrylic artificial tooth into each at least one tooth socket to produce an assembled intermediate product; and then (c) baking said assembled intermediate product for a time sufficient to cure said heat polymerizable component in said denture base and the dual cure resin in uncured or partially cured form in said at least one tooth socket, bond said tooth into each at least one socket with said cure, and produce said flexible partial denture.

In some embodiments, the resin comprises or consists essentially of a mixture of (i) a reactive blocked prepolymer comprising a compound of the formula A-X-A, where X is a hydrocarbyl group and each A is an independently selected substituent of Formula X:
<CHM>
where R is a hydrocarbyl group, R' is O or NH, and Z is a blocking group, said blocking group having a reactive epoxy, alkene, alkyne, or thiol terminal group, (ii) a chain extender (e.g., a polyamine and/or polyol chain extender), (iii) a photoinitiator, (iv) a reactive diluent, (v) a reactive blocked diisocyanate, (vi) optionally, but in some embodiments preferably, a reactive crosslinker; (vii) optionally, but in some embodiments preferably, at least one pigment or dye; and (viii) optionally, but in some embodiments preferably, an ultraviolet light absorber.

Also provided is a flexible partial denture produced by the process described herein.

Further provided is a resin composition comprising or consisting essentially of a mixture of (i) a reactive blocked prepolymer comprising a compound of the formula A-X-A, where X is a hydrocarbyl group and each A is an independently selected substituent of Formula X:
<CHM>
where R is a hydrocarbyl group, R' is O or NH, and Z is a blocking group, said blocking group having a reactive epoxy, alkene, alkyne, or thiol terminal group, (ii) a chain extender (e.g. MACM), (iii) a photoinitiator, (iv) a reactive diluent, (v) a reactive blocked diisocyanate, (vi) optionally, but in some embodiments preferably, a reactive crosslinker; (vii) optionally, but in some embodiments preferably, at least one pigment or dye; and (viii) optionally, but in some embodiments preferably, an ultraviolet light absorber.

The present invention is now described more fully hereinafter with reference to the accompanying drawings, in which embodiments of the invention are shown. This invention may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather the scope of the invention is defined by the claims.

As used herein, the term "and/or" includes any and all possible combinations of one or more of the associated listed items, as well as the lack of combinations when interpreted in the alternative ("or").

While the denture bases described herein can be made with any suitable resin, dual cure resins are currently preferred for carrying out the present invention. Such resins are known and described in, for example, <CIT>, <CIT> and <CIT>.

In general, such resins comprise a light polymerizable component and a heat polymerizable component. The heat polymerizable component preferably comprises precursors to a polyurethane, polyurea, or copolymer thereof. Examples of suitable dual cure resins include, but are not limited to, Carbon Inc. flexible polyurethane dual cure resins, available from Carbon, Inc. , <NUM> Mills Way, Redwood City, California <NUM> USA.

Light-polymerizable monomers and/or prepolymers. Sometimes also referred to as "Part A" of the resin, these are monomers and/or prepolymers that can be polymerized by exposure to actinic radiation or light. This resin can have a functionality of <NUM> or higher (though a resin with a functionality of <NUM> can also be used when the polymer does not dissolve in its monomer). A purpose of Part A is to "lock" the shape of the object being formed or create a scaffold for the one or more additional components (e.g., Part B). Importantly, Part A is present at or above the minimum quantity needed to maintain the shape of the object being formed after the initial solidification during photolithography.

Examples of suitable reactive end groups suitable for Part A constituents, monomers, or prepolymers include, but are not limited to: acrylates, methacrylates, α-olefins, N-vinyls, acrylamides, methacrylamides, styrenics, epoxides, thiols, <NUM>,<NUM>-dienes, vinyl halides, acrylonitriles, vinyl esters, maleimides, and vinyl ethers.

An aspect of the solidification of Part A is that it provides a scaffold in which a second reactive resin component, termed "Part B," can solidify during a second step, as discussed further below.

Heat-polymerizable monomers and/or prepolymers. Sometimes also referred to as "Part B", these constituents may comprise, consist of or consist essentially of a mix of monomers and/or prepolymers that possess reactive end groups that participate in a second solidification reaction during or after the Part A solidification reaction, preferably a heat cure (e.g., by baking). In some embodiments, the second component of the dual cure resin comprises precursors to a polyurethane, polyurea, or copolymer thereof (e.g., poly(urethane-urea)).

Examples of dual cure photopolymerizable reactive prepolymers include isocyanate or blocked isocyanate-containing prepolymers. A blocked isocyanate is a group that can be deblocked or is otherwise available for reaction as an isocyanate upon heating, such as by a urethane reaction of an isocyanate with alcohol. See, e.g., <CIT>; <CIT>; <NPL>).

"Isocyanate" as used herein includes diisocyanate, polyisocyanate, and branched isocyanate. "Diisocyanate" and "polyisocyanate" are used interchangeably herein and refer to aliphatic, cycloaliphatic, and aromatic isocyanates that have at least <NUM>, or in some embodiments more than <NUM>, isocyanate (NCO) groups per molecule, on average. In some embodiments, the isocyanates have, on average, <NUM>, <NUM>, <NUM>, <NUM>, or <NUM> isocyanate groups per molecule, up to <NUM>, <NUM> or <NUM> or more isocyanate groups per molecule, on average. In some embodiments, the isocyanates may be a hyperbranched or dendrimeric isocyanate (e.g., containing more than <NUM> isocyanate groups per molecule, on average, up to <NUM> or <NUM> more more isocyanate groups per molecule, on average). Common examples of suitable isocyanates include, but are not limited to, methylene diphenyl diisocyanate (MDI), toluene diisocyanate (TDI)), para-phenyl diisocyanate (PPDI), <NUM>,<NUM>'-dicyclohexylmethane- diisocyanate (HMDI), hexamethylene diisocyanate (HDI), isophorone diisocyanate (IPDI), triphenylmethane-<NUM>,<NUM>'<NUM>"-triisocyanate, tolune-<NUM>,<NUM>,<NUM>- triyl triisocyanate, <NUM>,<NUM>,<NUM>-triazine-<NUM>,<NUM>,<NUM>-triisocyanate, ethyl ester L-lysine triisocyanate, etc., including combinations thereof. Numerous additional examples are known and are described in, for example, <CIT>; <CIT>; <CIT>; <CIT>, <CIT>, and in US Patent Application Publication Nos. <CIT> and <CIT>: <CIT>.

The blocking group may optionally have a reactive terminal group (e.g., a polymerizable end group such as an epoxy, alkene, alkyne, or thiol end group, for example an ethylenically unsaturated end group such as a vinyl ether).

In some embodiments, the dual cure resin includes a UV-curable (meth)acrylate blocked polyurethane/polyurea (ABPU). Such resins are described in, for example, <CIT>, <CIT>, and<CIT>.

In some embodiments, the isocyanate may be blocked with an amine methacrylate blocking agent (e.g., tertiary-butylaminoethyl methacrylate (TBAEMA), tertiary pentylaminoethyl methacrylate (TPAEMA), tertiary hexylaminoethyl methacrylate (THAEMA), tertiary-butylaminopropyl methacrylate (TBAPMA), maleimide, and mixtures thereof (see, e.g., <CIT>)). Note that these could be used as diluents, as well.

Chain extenders. Chain extenders are generally linear compounds having di- or polyfunctional ends that can react with a monomer/prepolymer or crosslinked photopolymerized polymer intermediate as taught herein. Examples include, but are not limited to, diol or amine chain extenders, which can react with isocyanates of a de-blocked diisocynate-containing polymer.

Examples of diol or polyol chain extenders include, but are not limited to, ethylene glycol, diethylene glycol, triethylene glycol, tetraethylene glycol, propylene glycol, dipropylene glycol, tripropylene glycol, <NUM>,<NUM>-propanediol, <NUM>,<NUM>-butanediol, <NUM>,<NUM>-butanediol, neopentyl glycol, <NUM>,<NUM>-hexanediol, <NUM>,<NUM>-cyclohexanedimethanol, hydroquinone bis(<NUM>-hydroxyethyl) ether (HQEE), glycerol, trimethylolpropane, <NUM>,<NUM>,<NUM>-hexanetriol, and pentaerythritol. Natural oil polyols (biopolyols) may also be used. Such polyols may be derived, e.g., from vegetable oils (triglycerides), such as soybean oil, by known techniques. See, e.g., <CIT>.

Examples of diamine or polyamine chain extenders include, but are not limited to, aliphatic, aromatic, and mixed aliphatic and aromatic, polyamines, such as diamines (for example, <NUM>,<NUM>'-methylenedicyclohexanamine (PACM), <NUM>,<NUM>'-methylenebis(<NUM>-methylcyclohexylamine) (MACM), ethylene diamine, isophorone diamine, diethyltoluenediamine), and polyetheramines (for example JEFFAMINE® from Huntsman Corporation).

Diluents as known in the art are compounds used to reduce viscosity in a resin composition. Reactive diluents undergo reaction to become part of the polymeric network. In some embodiments, the reactive diluent may react at approximately the same rate as other reactive monomers and/or prepolymers in the composition. Reactive diluents may include aliphatic reactive diluents, aromatic reactive diluents, and cycloaliphatic reactive diluents. Examples include, but are not limited to, isobomyl acrylate, isobomyl methacrylate, lauryl acrylate, lauryl methacrylate, <NUM>-ethyl hexyl methacarylate, <NUM>-ethyl hexyl acrylate, di(ethylene glycol) methyl ether methacrylate, phenoxyethyl methacrylate, hydroxyethyl acrylate, hydroxyethyl methacrylate, dimethyl(aminoethyl) methacrylate, butyl acrylate, butyl methacrylate, cyclohexyl methacrylate, tetrahydrofurfuryl methacrylate, ethylene glycol dimethacrylate, hexanediol dimethacrylate, and tert-butylaminoethyl methacrylate.

In some embodiments, crosslinking diluents (i.e., having a functionality of <NUM> or more) may be used. Examples of such crosslinking diluents include but are not limited to a dimethacrylate such as neopentyl glycol dimethacrylate (NPGDMA), ethylene glycol dimethacrylate (EGDMA), etc..

In some embodiments, crosslinking agents may be included in the resin, which agent may be a crosslinking diluent (as noted above), or an agent that increases the resin viscosity. Examples of such crosslinking agents include but are not limited to a urethane dimethacrylate such as isophorone urethane dimethacrylate (UDMA), available from Esstech Inc. , Essington, Pennsylvania, USA as their product X-<NUM>-<NUM>.

Photoinitiators useful in the present invention include, but are not limited to, diphenyl(<NUM>,<NUM>,<NUM>-trimethylbenzoyl)phosphine oxide (TPO), Phenylbis(<NUM>,<NUM>,<NUM>-trimethylbenzoyl)phosphine oxide (PPO), <NUM>-isopropylthioxanthone and/or <NUM>-isopropylthioxanthone (ITX), etc..

The liquid resin can have additional ingredients solubilized therein, including pigments, dyes, active compounds or pharmaceutical compounds, detectable compounds (e.g., fluorescent, phosphorescent, radioactive), etc..

Ultraviolet light absorbers that can be used in the present invention include polysubstituted linear polyacenes such as described in <CIT>).

Denture bases can be produced in a "green" form from resins described above by additive manufacturing techniques.

Techniques for producing an intermediate object, or "green" intermediate, from such resins by additive manufacturing are known. Suitable techniques include bottom-up and top-down additive manufacturing, generally known as stereolithography. Such methods are known and described in, for example, <CIT>, <CIT> and <CIT>, <CIT>, <CIT>, <CIT>, <CIT>, and <CIT>.

In some embodiments, the additive manufacturing step is carried out by one of the family of methods sometimes referred to as continuous liquid interface production (CLIP). CLIP is known and described in, for example, <CIT>; <CIT>; <CIT>; and others; in <NPL>); and in <NPL>). Other examples of methods and apparatus for carrying out particular embodiments of suitable methods of making include, but are not limited to: <CIT>;<CIT>;<CIT>; <CIT>; <CIT>; <CIT> (see also <CIT> and <CIT>);<CIT> (see also US Pat. <CIT>); <CIT>); <CIT>); and<CIT>).

Once the denture base has been produced in a "green" form as described above, it may be optionally cleaned (e.g., by wiping, blowing, spinning, washing, etc.), and used to assemble a denture as discussed further below. If cleaned, in some embodiments it may be cleaned under conditions in which uncured or partially-cured resin is retained in the denture base sockets (or added back to denture base sockets) to bond the artificial teeth to the finished object as discussed below.

The same dual cure resin as used to form the denture base can advantageously be used to bond acrylic artificial teeth into that base. Partial dentures as used herein can include a plurality of teeth, for example <NUM>, <NUM>, or <NUM> or more teeth, but not an entire set of teeth.

As noted above, in some embodiments the denture base in green form may be cleaned under conditions in which uncured or partially-cured resin is retained in the denture base sockets (or added back to denture base sockets) to bond the artificial teeth to the finished object as discussed below. Additional uncured resin may be added to the sockets, if desired. Alternatively, the denture base may be cleaned to remove most or all of the residual resin, followed by addition of uncured resin to the sockets before or during insertion of the artificial teeth.

As shown in <FIG>, acrylic artificial teeth <NUM> are inserted into the sockets <NUM> of a denture base <NUM>, while the base is in a "green" form, to produce an assembled intermediate. That intermediate can then optionally be cleaned (in like manner as described above), and then heated or baked in accordance with known techniques to both further cure the base (and achieve the desired tensile properties therein) and bond the artificial teeth to the base.

In some embodiments, the denture base with inserted artificial teeth and uncured resin in the sockets is subjected to a "flood" UV cure to polymerize the resin, optionally prior to the baking step.

Additional processing steps such as removal of supports, grinding or polishing of edges or surfaces and the like, can be performed before or after assembly of the complete denture, in accordance with known techniques.

Any type of acrylic artificial tooth can be used in the methods and products described herein, including those formed from a conventional acrylic resin and those formed from a modified acrylic resin. The resin and artificial tooth can incorporate cross-linking agents to enhance mechanical strength, can include copolymers or poly(methyl methacrylate), can include an interpenetrating polymer network, etc. In some embodiments the teeth can be manufactured using multilayered or double cross-linked material. The tooth can include additional constituents such as ultra-high molecular weight polyethylene, inorganic microparticle fillers (such as a microfiller-reinforced polyacrylic), and can include layers with a pearly effect to provide a more natural appearance. See generally <NPL>); see also <CIT>; <CIT>; and <CIT>. Commercial sources for acrylic artificial teeth include: Ivoclar Vivadent Inc. , <NUM> Pineview Drive, Amherst, NY <NUM> USA; Candulor AG, Boulevard Lilienthal <NUM>, <NUM> Glattpark (Opfikon), Switzerland; Kulzer GmbH, <NUM>. Lafayette Blvd. , South Bend, IN <NUM> USA; and others. In some embodiments the artificial tooth itself may be produced by additive manufacturing, such as (for example) a DENTCA™ artificial tooth. Y-J Chung et al. , 3D printing of resin material for denture artificial teeth: Chipping and indirect tensile fracture resistance, Materials (Basel) <NUM>(<NUM>): <NUM> (<NUM>).

In some embodiments, the flexible partial denture base after baking has a tensile modulus of from <NUM> to <NUM> MPa (e.g., with ASTM D638: Tensile Testing) (e.g., <NUM>-<NUM> MPa, or <NUM>-<NUM> MPa), and/or an Izod impact strength of from <NUM> to <NUM> J/m<NUM> (e.g., with ASTM D256: Izod Impact Testing) (e.g., <NUM>-<NUM> J/m<NUM>, or <NUM>-<NUM> J/m<NUM>).

Non-limiting examples are given below, where the following abbreviations are used:.

Resin formulations were mixed by first adding NPGDMA, IBOMA and UDMA to a THINKY™ mixer cup with the TPO and DBA, then mixing at <NUM> RPM until all the solids were dissolved (~<NUM> minutes). Then the ABPU and any pigment components were added and mixed for <NUM> minutes at <NUM> RPM. Finally, the amine components (MACM and, where present, D2000) were added and mixed for <NUM> minutes.

This resin was prepared in the manner described above from the ingredients set forth in Table <NUM> below. The specific ABPU was prepared from the constituent ingredients in the molar ratios indicated in the table in accordance with known techniques such as given in <CIT>.

This resin was prepared in the manner described above from the ingredients set forth in Table <NUM> below. The specific ABPU was prepared from the constituent ingredients in the molar ratios indicated in the table in accordance with known techniques such as given in <CIT>.

The resin formulations described in Examples <NUM>-<NUM> above were placed in the cassette of Carbon Inc. additive manufacturing apparatus and samples were printed. After printing, the samples were cleaned in <NUM>% isopropyl alcohol for <NUM> minutess on an orbital shaker table, then dried at room temperature. They were then cured in a Dreve PCU-LED UV cure box for <NUM> minute at a wavelength of <NUM>, under a nitrogen atmosphere. The samples were then baked at <NUM> for <NUM> hours.

The Modulus of elasticity, and the Notched Izod Impact Resistance, of samples prepared from resin formulations <NUM>-<NUM> were tested in accordance with known techniques. Results are given in <FIG>.

Resin formulation <NUM> is among those currently preferred because of its high modulus of elasticity (though greater impact strength would in some embodiments be preferred).

Resin formulation <NUM> is also among those currently preferred because, although its modulus of elasticity is somewhat lower than that of formulation <NUM>, it was found to be easier to manufacture than resin formulation <NUM>.

Claim 1:
A method of making a flexible partial denture, comprising:
(a) producing a partial denture base (<NUM>) by additive manufacturing from a dual cure resin, with the dual cure resin comprising a light polymerizable component and a heat polymerizable component, with the denture base (<NUM>) including at least one tooth socket (<NUM>) comprising the dual cure resin in uncured or partially cured form;
(b) inserting an acrylic artificial tooth (<NUM>) into each at least one tooth socket (<NUM>) to produce an assembled intermediate product; and then
(c) baking said assembled intermediate product for a time sufficient to cure said heat polymerizable component in said denture base (<NUM>) and the dual cure resin in uncured or partially cured form in said at least one tooth socket (<NUM>), bond said tooth (<NUM>) into each at least one socket (<NUM>) with said cure, and produce said flexible partial denture.