Printable, ester-based resin compound and printing method using the same

专利摘要:
The present invention relates to a resin compound particularly suitable for printing, a set comprising the chemical compounds of the resin compound, a printing process using the resin compound, a polymer obtained by the printing process, an article which the polymer comprises or is formed from the same, and uses thereof. The resin compound can be particularly suitable for printing and has the following: at least one chemical compound C1 which has (i) at least one terminal functional alkyne group and (ii) at least one functional ester group, and at least one chemical compound C2 which has at least two functional thiol groups.
公开号:AT521571A2
申请号:T9419/2016
申请日:2016-10-12
公开日:2020-02-15
发明作者:Österreicher Andreas；Dr Griesser Thomas；edler Matthias；Mostegel Florian；Roth Meinhart
申请人:Montanuniv Leoben；
IPC主号:

专利说明:

Printable, ester-based resin compound and printing method using the same
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a resin compound particularly suitable for printing, a kit comprising the constituents of the resin compound, a printing method using the resin compound, a polymer obtained by the printing method, an article which Includes or is formed from polymer and uses thereof.
BACKGROUND
Printing processes can serve a wide variety of purposes. In addition to conventional two-dimensional printing methods that are still widely used, three-dimensional printing methods have gained increasing interest in recent years. While they were originally developed for the production of prototypes, for example for design purposes, three-dimensional (3D) printing methods are now being used more and more for the production of highly complicated and complex geometric structures that are brought onto the market, for example in the automotive industry Manufacture of ornaments (or ornaments) and in end-user applications (Wendel et al., Macromol. Mater. Eng. 293 (2008) 799-809).
Among the well-known 3D printing processes is the so-called solid-free molding technology or rapid prototyping, such as fused deposition modeling (FDM), selective laser sintering (SLS) and 3D printing technology (3DP), especially stereolithography (SLA) very promising technology with regard to its high resolution, which is hardly possible with AD: SK: sc
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- 2 other techniques can be achieved (Gross et al., Anal. Chem. 86 (2014) 3240-3253; Liska et al., J. Coat. Technol. Res. 4 (2007) 505-510). This technique, based on photopolymerization, is particularly suitable for displaying biomedical products, such as artificial, biodegradable bone structures, which require pore sizes between 100 μm and 500 μm (Lipowiecki et al., J. Biomed. Mater. Res. Part A (2014) , accepted; Bose et al., Materials Today 16 (2013) 496-504). Previous bone substitute materials made by FDM, SLS or 3DP are mainly based on ceramic materials such as calcium phosphate or hydroxyapatite, but they suffer from a low mechanical load capacity with increasing porosity.
Typical biodegradable polymers that are used as surgical sutures, especially for surgical wound suturing, are based on polyester polymers, for example polycaprolactones (e.g. poly (e-caprolactone)) and poly (a-hydroxy acids) (e.g. polyglycolic acid, polylactic acid and copolymers thereof). . However, due to their rapid hydrolytic degradation, which leads to a loss of their mechanical properties, these materials cannot be used as a replacement for hard tissue.
Among the photo-reactive, biodegradable polymers, poly (propylene fumarate) and poly (trimethylene carbonate-co-caprolactone) coumarin have proven to be suitable for producing porous structures using SLA (Melchels et al., Biomaterials 31 (2010) 6121-6130 ; Cooke et al., J. Biomed. Mater. Res. Part B: Appl. Biomater. 64B (2003) 65-69; Lee et al., Biomacromolecules 8 (2007) 1077-1084; Matsuda et al., Macromolecules 33 (2000) 795-800). Microneedles prepared from SLA of acrylated poly (trimethylene carbonate-co-caprolactone) were implanted subcutaneously in rats for one month and showed regular degradation by surface erosion, similar to that of alkaline hydrolysis (Matsuda et al., J. Biomed Mater Res. 62 (2002) 395-403). Liska et al. have evaluated a variety of photo-reactive polymers as resins used for stereolithography and two-photon absorption (TPA) photopolymerization, respectively, for manufacturing cellular structures. The monomers mainly based on acrylates, methacrylates and acrylamides
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- 3, have been shown to be non-cytotoxic and could be structured with stereolithographic methods using digital light processing (DLP) or UV laser micro stereolithography with a resolution of 5 to 10 μm (Liska et al., J. Coat. Technol. Res. 4 (2007) 505-510; Schuster et al, Proceedings LPM 2007 - The 8 ^lh Symposium on Laser Precision Microfabrication).
Despite these efforts, the choice of conventionally available printing resins is still limited, so there is a need for the development of new materials and compositions.
Thiol-en reactions represent an established photopolymerization process that is used for a variety of applications, particularly in the optical, biomedical, bioorganic and dental fields (Hoyle et al., Angew. Chem. Int. Ed. 49 (2010) 5301- 5338). Advantages of thiolene reactions are high reactivity, insensitivity to oxygen, high chemical stability, low shrinkage of the polymers obtained and high polymerization yields (Hoyle et al., J. Polym. Sci. Part A: Polym. Chem. 42 (2004) 5301-5338). WO 2013/052328 A1 discloses resorbable, biocompatible polymers which have been formed by thiol-ene polymerization of vinyl esters and vinyl carbonates, it being possible for these polymers to be used as a biodegradable, resorbable implant.
Thiol-yn photopolymerizations operate with a mechanism similar to that of thiol-ene reactions, and consequently they have the same advantages. However, polymers obtained by thiol-yn reactions have a degree of crosslinking six times higher and consequently a significantly higher glass transition temperature than corresponding thiol-ene-based polymers (Fairbanks et al., Macromolecules 42 (2009) 211-217). Because of the ability of an alkyne residue to react with two thiol monomers, monofunctional monomers, such as chemical compounds that have only one alkyne residue, can be used in thiol-yn reactions without stopping the polymerization reaction. Thiol-yn-based polymers have high biocompatibility and are therefore suitable for the biomedical field. WHERE
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- 4 2012/103445 A2 discloses the representation of biodegradable hydrogels based on a thiol-yn reaction, which hydrogels are described as being suitable for biomedicine, in particular as a substance for the growth of different cell types. US 2011/0144227 A1 discloses biomedical devices which contain thiol-en or thiol-yn shape memory polymers.
OBJECT OF THE INVENTION
In view of the foregoing, the present invention aims to overcome the above described problems and disadvantages of previously available printing resins, particularly their limitations when used for medical or biomedical applications. Thus, it is an object of the present invention to provide a new resin compound which is particularly suitable for printing and which benefits from the advantages of thiolyn polymerization reactions. Another object is to provide a polymer and an article comprising or formed from the polymer, the polymer being highly biocompatible and biodegradable, having a very low residual monomer content and showing little shrinkage.
DISCLOSURE OF THE INVENTION
The present inventors have conducted careful studies to solve these objects, and have found that if the alkyne functional component in a resin compound further has at least one ester functional group, not only a printing ink having highly biocompatible monomers and excellent can be provided is suitable for 3D printing, such as stereolithography, which has a high curing speed of the resin and very high monomer conversion (thereby essentially avoiding any migration of monomers from the final product) and is insensitive to oxygen during the polymerization, but also the biological one Degradability of the resulting polymers, as well as an article comprising or made from the polymer, are suitable to that
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- 5 desired requirements of a specific medical or biomedical application can be set and the shrinkage of the resulting polymers is low due to the formation of a homogeneous network, as well as that the mechanical properties, such as the elastic modulus, are excellent due to the high degree of crosslinking, whereby these Properties are particularly advantageous in medical or biomedical applications, such as implantation, bone insertion or replacement, tissue insertion or replacement and / or dental applications. Furthermore, the compound and a printing process using the compound can be solvent-free, which further improves the biocompatibility of the resulting products due to the absence of any solvent. Furthermore, the compound can contain additives which can provide additional specific, tailored, advantageous properties of the resulting products, as may be desired.
Accordingly, the present invention relates to a resin compound comprising:
at least one chemical compound CI, comprising (i) at least one terminal (or terminal) functional alkyne (or acetylene or etine) group and (ii) at least one functional ester group, and at least one chemical compound C2 which has at least two functional thiols Groups.
The resin compound according to the present invention is particularly suitable for printing.
Accordingly, the present invention further relates to the use of the resin compound according to the present invention as or in an ink.
The chemical compounds CI and C2 of the resin compound according to the present invention can in particular be in a spatially separate manner
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- 6 are provided, for example in a set (k / t), in particular in a kit of parts.
Accordingly, the present invention also relates to a set comprising:
at least one chemical compound, comprising (i) at least one terminal (or terminal) functional alkyne (or acetylene or etine) group and (ii) at least one functional ester group, and at least one chemical compound C2 which has at least two functional thiols Has groups.
Furthermore, the present invention relates to the use of the kit according to the present invention for producing a resin compound for use as or in an ink.
The present invention further relates to a printing method comprising the following steps:
Providing the resin compound according to the present invention, the resin compound further comprising at least one initiator, and
Directing an energy source to at least a portion of the resin compound so that polymerization is effected from the at least a portion of the resin compound and so that a polymer is obtained.
In addition, the present invention relates to a polymer obtainable (or can be obtained) by the printing method according to the present invention.
uuS vvciiciuii ucxicrii i uic vunicyciiuc Liiiiiuuiiy dui cn ιυι i ru uisci, υυι uab polymer according to the present invention comprises or is formed therefrom.
The polymer and article obtained according to the present invention can be used for various applications.
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Accordingly, the present invention further relates to a use of the polymer or article according to the present invention in a medical or biomedical application.
Other objects and many of the associated advantages and embodiments of the present invention will be readily appreciated and better understood by reference to the following detailed description of embodiments and the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 is a graphical representation of the test results of Example 1 and shows the reaction rates of the alkyne monomers tested and the comparative (meth) acrylic monomers, and also shows their chemical structural formulas.
Figure 2 is a graphical representation of the conversion of the alkyne and alkene content respectively obtained during the photopolymerization of 1,4-butanediol dimethacrylate, 1,4-butanediol diacrylate, succinic acid dibut-1-ynyl ester and succinic acid dipropargyl ester using real-time FTIR measurements according to Example 2.
FIG. 3 shows representations of the concentration-dependent cytotoxicity after incubation for 48 hours of 1,4-butanediol diacrylate.
FIG. 4 shows representations of the concentration-dependent cytotoxicity after incubation for 48 hours of 1,4-butanediol dimethacrylate.
c! H! ! TR 7Pint inrinn dör '7 / ίτ> <- ηγί · 7ίί · ϋΙ · narh t lyui □ Zk-iyc LyMiJcc.uunyc.il jcn (XUI I ^ unci u cimi I jMUMMuy <yun xy cvcvÄil.icml nucn of an incubation for 48 hours of succinic acid dipropargylester.
FIG. 6 shows representations of the concentration-dependent cytotoxicity after incubation for 48 hours of succinic acid-dibut-1-ynylester.
DETAILED DESCRIPTION OF THE INVENTION
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- 8 The following describes details of the present invention and other features and advantages thereof. However, the present invention is not limited to the specific descriptions that follow, but these are for illustrative purposes only.
It should be noted that features described in connection with an exemplary embodiment or an exemplary aspect may be combined with all other exemplary embodiments or exemplary aspects, in particular features described by any exemplary embodiment of the resin compound may be combined are included with any exemplary embodiment of a kit, printing process, polymer or article, or with any exemplary embodiment of uses thereof and vice versa, unless specifically stated otherwise.
Where an indefinite or particular article is used, where a singular expression is referred to, such as an "a," one or "the, a majority of that expression is also included and vice versa, except where specifically is represented differently, whereas the word "one or the number" 1 as used herein typically means "only one or" exactly one.
The term "comprising or" comprising, as used herein, not only includes the meaning of "comprising," including or "containing, but also includes" consisting essentially of and "consisting of.
Except where specifically stated otherwise, the terms "at least partially," at least partially, or "at least a portion of, as used herein, mean: at least 5% thereof, particularly at least 10% thereof, particularly at least 15 % thereof, in particular at least 20% thereof, in particular at least 25% thereof, in particular at least 30% thereof, in particular at least 35% thereof, in particular at least 40% thereof, in particular at least 45% thereof,
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9 in particular at least 50% thereof, in particular at least 55% thereof, in particular at least 60% thereof, in particular at least 65% thereof, in particular at least 70% thereof, in particular at least 75% thereof, in particular at least 80% thereof, in particular at least 85% thereof, in particular at least 90% thereof, in particular at least 95% thereof, in particular at least 98% thereof, and can also mean 100% thereof.
In a first aspect, the present invention relates to a resin compound comprising:
at least one chemical compound CI, comprising (i) at least one terminal functional alkyne group and (ii) at least one functional ester group, and at least one chemical compound C2 which has at least two functional thiol groups.
The term "chemical compound, as used herein," may in particular mean that the constituents of the chemical compound are close to (and in close proximity to) one another and / or that the components are (intensively) mixed with one another, for example using a mixer, a stirrer and / or by shaking to thereby form the chemical compound. In particular, the constituents of the chemical compound can be uniformly distributed or dispersed within the composition (or chemical compound). The chemical compound can in particular be solid, semi-solid (mushy) or liquid, in particular a liquid solution or a semi-solid or liquid suspension.
The resin compound can in particular be a photo-reactive and / or a thermo-reactive resin compound. The term “photo-reactive” as used herein may mean in particular that the resin compound, in particular some or all of its components, undergo a (chemical) reaction when irradiated with an energy-carrying activation beam, in particular with electromagnetic radiation. The term “thermo-reactive, as used herein, may in particular mean that the resin compound, especially some or all of its components, undergo a (chemical) reaction
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10 when adding thermal energy to the resin compound, such as by heating and / or by irradiation with electromagnetic radiation in the infrared or microwave wavelength ranges.
The resin compound may be particularly suitable for printing, for example in a printing process according to the present invention. Accordingly, the resin compound can be used particularly as an ink (a printing ink), i.e. the resin compound itself can be used directly as an ink. Similarly, the resin compound can be used especially as an ink (a printing ink), i.e. as a constituent or ingredient of an ink along with one or more other suitable constituents or ingredients typically used as an ink.
The resin compound comprises at least two components (or chemical compound or ingredients: at least one chemical compound CI (also referred to as “yn component or“ yn monomer) and at least one chemical compound C2 (also referred to as “thiol component or thiol monomer As is evident, the resin compound may contain more than one chemical compound CI (such as a mixture of different chemical compounds CI) and / or more than one chemical compound C2 (such as mixtures of different chemical components C2) as well such as other ingredients or chemical compounds, which are described below.
The chemical compound Cl has (i) at least one terminal (or terminal) functional alkyne group, and (ii) at least one functional ester group.
The term "final alkyne functional group, as used herein and generally understood by one of ordinary skill in the art, represents a portion (or residue) having a carbon-carbon triple bond with one of the carbon atoms binding to a hydrogen atom. In other words, a final functional alkyne group can be represented by the general formula ,, - ChC-H. The final functional alkyne11 / 66
The group can also be present in a protected form, for example as a silyl (such as trimethylsilyl (TMS)) protected alkyne group and / or as a complex of the carbon-carbon triple bond with, for example, dicobalt octacarbonyl. Appropriate deprotection (or removal of the protecting group) should then be carried out, as is known to those skilled in the art, prior to use of the resin compound, for example in a printing process or in any other intended use in which it is intended that the final functional Alkyne group takes part in a thiol-yn reaction.
The term ester, as used herein, corresponds to its generally accepted meanings. An ester can be represented by the general formula “- (CO) O- or ,, - O (CO) -.
The functional ester group enables decomposition (or degeneration) of a product (such as a polymer or an article comprising or formed from the polymer) that is obtained after the thiol-yn reaction, for example by a printing process a human or animal body, such as when used as a medical or biomedical device. In addition to the functional ester group, the chemical compound CI may in particular further comprise: a carbonate, a carbamate and / or a functional ether group, which also have specific desired physiological properties of the product (such as its degree and rate (rate) of biological) Degradation under a physiological environment) can provide. Other functional groups that are more or less hydrolyzable / cleavable under physiological conditions can be found in the chemical compound CI, but also in the chemical compound
Compound C2 may be included. It could also be advantageous that the product is biodegradable and at least partially non-biodegradable, for example if certain persistent mechanical assistance is desired, or that part of the product biodegrades relatively quickly, whereas part of the product decomposes relatively slowly biodegrades, which could be particularly advantageous if the product is used as an implant, a bone replacement and / or a tissue replacement. Such
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- 12 products can in particular be derived from a resin compound, which comprise combinations of the chemical components CI and C2, which contain non-decomposable thiols.
The final functional alkyne group of the chemical compound CI can in particular be one which is selected from the group consisting of: propargyl, butynyl and pentynyl. Propargyl can be represented by the general formula -CH ₂ -CsC-H, butynyl can be represented by the general formula -CH ₂ -CH ₂ -ChC-H or -C (CH ₃ ) H-CsC-H, and pentynyl can are represented by the general formulas -CH ₂ -CH2-CH ₂ -C = CH, -C (CH ₃ ) H-CH ₂ -C = CH, -CH ₂ -C (CH ₃ ) HC = CH or -C ( CH ₃ ) ₂ -C = CH. The linear (unbranched) groups thereof, ie -CHj-CsC-H, -CH2-CH ₂ -C ^ CH and -CH ₂ -CH:> - CH ₂ -CsC-H can be preferred.
The present inventors had the (or the) unexpected realization (or result) that the larger the carbon atom chain of the terminal functional alkyne group, the higher the reactivity between the terminal functional alkyne group and a thiol group in a thiolyn- Reaction, and consequently the faster the resulting cross-linking takes place, which is advantageous for a printing process, in particular a three-dimensional printing process, where typically the object to be printed is formed layer by layer, which requires the preceding layer to be essentially cured or dried (solidified) is before the subsequent layer is formed. Thus, the printing time can be shortened with an increasing number of carbon atoms in the final functional alkyne group. On the other hand, the present inventors have found that the larger the carbon atom chain of the final functional alkyne group, the more flexible the shaped _Ä u ,. ~ I> U ΙζληηΑΗ Hir »morh Onicrhon Pinoncrh ^ f + on dor vei I ICLZ-Uliyei l ÖIIIU, UI1U lUiyilVIl ^ lincu Ulk. ΐί «κ_κ_> IUI icn I u« - · .V4. vv. The resulting (polymer) crosslinking, in particular its mechanical strength and hardness, are impaired, which is not desirable if a certain shape and mechanical integrity of the corresponding product or article is an important point, for example if it is used as an implant, a bone substitute and / or a dental product, such as a dental product
Prosthesis is used.
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13 A final functional alkyne group of the chemical compound CI of any one selected from the group consisting of propargyl, butynyl and pentynyl has been found to be very suitable for the purposes of the present invention. In particular, a terminating functional alkyne group of the chemical compound CI of butynyl and / or pentynyl may be preferred with regard to a rate of polymerization. In particular, a butynyl group as the at least one final functional alkyne group is particularly advantageous with regard to the rate of polymerization and the mechanical properties of the polymer network formed.
In one embodiment, the at least one chemical compound CI can comprise a chemical compound that has a functional group that is selected from the group consisting of a propargyl ester, a butynyl ester and a pentynyl ester. In particular, the at least one chemical compound CI can comprise a chemical compound that has a functional group that is selected from the group consisting of a butynyl ester and a pentynyl ester.
In one embodiment, the at least one chemical compound CI can be represented by one of the following general formulas (I) to (III):

(JXf) where n, m and o represent an integer from 1 to 1000, and
R ¹ , R ² and R ³ independently represent one of the following: a linear or branched, saturated or unsaturated, substituted or unsubstituted alkyl group, a linear or branched, saturated or unsaturated, substituted or unsubstituted heteroalkyl group, a saturated or unsaturated, substituted or unsubstituted cycloalkyl group, a saturated or unsaturated, substituted or unsubstituted heterocycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a linear or
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14 branched, substituted or unsubstituted aralkyl group, or a linear or branched, substituted or unsubstituted alkaryl group.
In the general formulas (I) to (III), n, m and o can in particular represent an integer from 1 to 1000, with a lower range limit of, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25 and / or with an upper range limit of, for example, 1000, 900, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 275, 250, 225, 200, 190, 180, 170, 160, 150, 140, 130, 125, 120, 115, 110, 105, 100, 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 38, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, 2, including any simple combination of the lower and upper range limit values.
The meanings of the terms "linear," branched, "saturated," unsaturated and "unsubstituted," as used herein, correspond to their respective established meanings as known to those skilled in the art. The term “substituted, as used herein, means that one or more, in particular 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, hydrogen atoms of the corresponding groups are substituted by a substituent. Examples of suitable substituents include halogen atoms such as -F, -CI, -Br, -I; -OH, hydroxyalkyl groups (ether), SH, thioalkyl groups (thioether), -O, carboxyl groups (-COOH) and salts, esters and amides thereof, -NHz, secondary amine groups, tertiary amine groups, nitrile - Groups and nitro groups. When two or more substituents are present, they can be the same or different and they can be linked together to form a ring. The terms “heteroalkyl group,“ heterocycloalkyl group ”or“ heteroaryl group, respectively, represent an alkyl group, a cycloalkyl group or an aryl group, respectively, wherein one or more, in particular 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10, carbon atoms are replaced by a hetero atom, such as Ο, N or S, in particular O and / or N. If more than one hetero atom is contained in a group, these hetero atoms can be the same or different.
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Suitable examples of the alkyl group include Ci to C ₂₀ alkyl groups, in particular C ₂ to Cw alkyl groups, in particular C ₂ to Cs alkyl groups, in particular Cs to C ₆ alkyl groups.
Suitable examples of the cycloalkyl group include C ₃ to C ₂₀ cycloalkyl groups, in particular Cs to Cjs cycloalkyl groups, in particular Cs to Cio cycloalkyl groups, in particular Ce to C ₈ cycloalkyl groups.
Suitable examples of the aryl group include Ce to C ₂ o aryl groups, especially C _& Cis aryl groups, especially Ce to Cis aryl groups, especially Cs to Cw aryl groups. In particular, the aryl group can be a phenyl group.
An “aralkyl group, as used herein, means a group having an aliphatic and an aromatic part, the aliphatic part being attached to a functional ester group of the corresponding chemical compounds represented by the general formulas (I) to (III) are shown, binds, and wherein the aromatic part and / or the aliphatic part may optionally comprise a heteroatom. In other words, an “aralkyl group” represents an alkyl or cycloalkyl group (or a heteroalkyl or heterocycloalkyl group) that has an aryl group (or a heteroaryl group) as a substituent. Suitable aliphatic and aromatic parts of the aralkyl group correspond to the alkyl, cycloalkyl and aryl groups (or heteroalkyl, heterocycloalkyl and heteroaryl groups, respectively) as defined above.
An “alkaryl group, as used herein, means a group having an aliphatic and an aromatic part, the aromatic part being bonded to a functional ester group of the corresponding chemical compounds represented by the general formulas (I) to (III) , and wherein the aliphatic part and / or the aromatic part may optionally comprise a hetero atom. In other words, an "alkyl group represents an aryl group (or a heteroaryl group) having an alkyl or cycloalkyl group (or a heteroalkyl or heterocycloalkyl group) as a substituent. Suitable aliphatic and aromatic parts of the alkaryl group
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- 16 correspond to the alkyl, cycloalkyl and aryl groups (or heteroalkyl, heterocycloalkyl and heteroaryl groups, respectively) as defined above.
In one embodiment, the at least one chemical compound CI has a terminal functional alkyne group, where, for example, n, m and o in the above general formulas (I) to (III) are equal to 1. It should be noted that due to the presence of a carbon-carbon triple bond in the yn monomer, a monofunctional alkyne monomer with two functional thiol groups can react in a thiol-yn reaction, so that the polymerization reaction can continue (not end) even if only one functional alkyne group is present in the yn monomer.
In one embodiment, the at least one chemical compound CI has at least two terminal functional alkyne groups, such as 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16 , 17, 18, 19, 20 or more terminal functional alkyne groups. Such chemical compounds CI can be particularly advantageous if a low viscosity of the resin compound is not required and / or where a particularly strong polymer network with a large variety of cross-links is desired.
Suitable examples of the at least one chemical compound CI include, for example, the following chemical compounds:
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The chemical compounds CI, as defined herein, can be prepared by established organic synthetic methods using commercially available starting materials.
For example, a chemical compound that has at least one terminating alkyne functional group and at least one ester functional group can be represented, as more specifically below
Examples is shown. It should be noted that these specific examples are for illustrative purposes only and should not be construed as limiting in any way. An approach to synthesizing chemical compounds that have at least one terminating functional alkyne group and at least one functional ester
Group, according to a Schotten-Baumann esterification synthesis is illustrated below:
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- 18 As an alternative approach to the above process, the following process for synthesizing chemical compounds that have at least one terminating functional alkyne group and at least one functional ester group using a Steglich esterification synthesis is shown below:
As a further example, a chemical compound which has at least one terminating functional alkyne group and at least one functional ester group can be represented by means of a Fischer-Speier esterification synthesis, as shown below:

TiOpoclv Dean-Stark catcher
Xylene, carbon black
The chemical compound C2 has at least two functional thiol groups.
The term "functional thiol group, as used herein and generally understood by one of ordinary skill in the art, represents a functional group represented by the general formula" -SH, which may also be present in a protected form, which is represented, for example, by the general formula “-SZ, where“ Z represents a protective group for “-SH, ie a thiol protecting group.
In one embodiment, at least one of the functional thiol groups comprises a thiol protecting group. In other words, at least one of the functional thiol groups may be in protected form or at least one of the functional thiol groups may be represented by the general formula "-SZ," Z representing a protecting group for "-SH, i.e. a thiol protection group. The thiol protective group can in particular be selected from
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- 19 of the group consisting of: an acyl group, a silyl group and a siloxyl group. In the case of an acyl-thiol protective group, the functional thiol group is in particular a thioester. In the case of a silyl protective group, the functional thiol group is in particular a silylthioether. In the case of a siloxyl thio protective group, the functional thiol is Group is in particular a silyl thioester.
Suitable examples of an acyl thiol protecting group include formyl and acetyl. Suitable examples of a silyl thiol protecting group include trimethylsilyl, triethylsilyl, tert-butyldimethylsilyl, tert-hexylsilyl, trihexylsilyl and tripropylsilyl. Suitable examples of a siloxyl thiol protecting group include trimethylsiloxyl, triethylsiloxyl, t-butyldimethylsiloxyl, tert-hexylsiloxyl, trihexylsiloxyl and tripropylsiloxyl.
Appropriate deprotection (ie deprotection) should then be carried out, as is known to those skilled in the art, prior to use of the resin compound, for example in a printing process or in any other intended use thereof in which it is intended that the functional thiol Group participates in a thiol-yn reaction. For example, in the case of a silyl thiol protecting group (a silyl thioether) deprotection can be carried out by reaction with a photo acid, i.e. a chemical compound that produces an acid when irradiated with electromagnetic radiation. Likewise, in the case of an acyl or a silyl thiol protecting group (a thioester or a silyl thioester), deprotection by reaction with a photobase, i.e. a chemical compound that generates a base under irradiation with electromagnetic radiation.
______ j ______ G-jri'- 'i-J-mwörhinHi mn fornor minHpQtpnc; ΡΙΠΡ PhotOSäUTP ueniei iibpi eci ici iu καΠίι uic i .............. * · ”..........
and / or comprise at least one photobase. In particular, in the case of a silyl thiol protecting group (a silyl thioether) the resin compound may further comprise at least one photo acid, and in the case of an acyl or a silyl thiol protecting group (a thioester or a silyl thioester) the resin compound further comprise at least one photo base.
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- 20 Suitable examples of a photo acid (photo acid generator, PAG) include:
Ionic photo acid generators, in particular: onium salts, such as onium salts of aryldiazonium, diaryliodonium (e.g. Cyracure UVI-6976 available from The Dow Chemical Company, Esacure 1064 available from Lamberti SpA, QL Cure 211 available from CHANGZHOU TRONLY NEW ELECTRONIC MATERIALS CO. , LTD), triarylsulfonium (e.g. Omnicat 440 available from IGM Resins BV, Irgacure 250 available from BASF SE, Rhodorsil 207 available from Rhodia), triarylselenonium or triarylphosphonium salts which contain complex halides, such as BF /, SbFö ', AsF ₆ ', B (C6Fs) 4' or PF _Ö as counterions, Eisenaren complexes (eg Irgacure 261 available from BASF SE) which contain complex halides, such as BF /, SbF ₆ , AsF ₆ ', B (C ₆ F ₅ ) 4' or PFö as counterions; Dialkylphenacylsulfonium salts containing complex halides such as BFf, SbF ₆ ', AsF _b , B (C ₆ F ₅ ) 4' or PF &'as counterions
- Non-ionic photo acid generators, in particular o 2-nitrobenzyl esters of carboxylic acids c 2-nitrobenzyl esters of sulfonic acids: sulfone compounds that generate sulfinic acid under UV radiation:> triaryl phosphates o N-hydroxyimide sulfonates (e.g. N-hydroxy-5-norbornen- 2,3-dicarboximide-perfluoro-l-butanesulfonate) c, sulfonic acid ester of phenol Diazonaphthoquinones o iminosulfonates o trichloromethyl-l, 3,5-triazines (e.g. 2- (4-methoxystyryl) -4,6bis (trichloromethyl) -l, 3,5-triazine) and / or mixtures of any of the foregoing.
Suitable examples of a photobase (photobase generator, PBG) include
- Carbamates (e.g. m-nitrophenyl, 3,5-dimethoxybenzyl, l-methyl-l- (3,5dimethoxyphenyl) ethyl, α-methylnitropiperonyl, o-nitrobenzyl, 3,4-dimethoxy-6-nitrobenzyl, phenyl (o-nitrophenyl) methyl , 2- (2-
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- 21 nitrophenyl) ethyl, 6-nitroveratryl, 4-methoxyphenacyl, 3'5'Dimethoxybenzoincarbamate)
o-acyl oximes
- ammonium salts
- sulfonamides
- formamides
- Nifedipine
- aminimides
a-aminoketones
o-carbamoyloximes and / or mixtures of any of the foregoing.
In one embodiment, the at least one chemical compound C2 can be represented by the following general formula (XIII):
X-fL-SZ] ₂ (XIII) where z represents an integer from 2 to 1000,
Z - independently of each other at each occurrence - represents hydrogen or a thiol protective group,
L - independently at each occurrence - represents a single bond or represents a divalent group selected from the group consisting of: a linear or branched, saturated or unsaturated, substituted or unsubstituted alkylene group, a linear or branched, saturated or unsaturated, substituted or unsubstituted heteroalkylene group, a saturated or unsaturated, substituted or unsubstituted cycloalkylene group, a saturated or unsaturated, substituted or unsubstituted heterocycloalkylene group, a substituted or unsubstituted arylene group, a substituted or unsubstituted heteroarylene group a linear or branched, substituted or unsubstituted aralkylene group, a linear or branched, substituted or unsubstituted alkarylene group, or a silicon-containing divalent group, and
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22 X represents a z-valent group selected from the group consisting of: a linear or branched, saturated or unsaturated, substituted or unsubstituted alkyl group, a linear or branched, saturated or unsaturated, substituted or unsubstituted heteroalkyl Group, a saturated or unsaturated, substituted or unsubstituted cycloalkyl group, a saturated or unsaturated, substituted or unsubstituted heterocycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a linear or branched, substituted or unsubstituted aralkyl group, a linear or branched, substituted or unsubstituted alkaryl group, or a silicon-containing z-valent group.
In the general formula (XIII), z can in particular represent an integer from 2 to 1000, with a lower range limit of, for example, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50 and / or with an upper range limit of, for example, 1000, 900, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 275, 250, 225, 200, 190, 180, 170, 160, 150, 140, 130, 125, 120, 115, 110, 105, 100, 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 38, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3, including any combination of the lower and upper range limits.
The definitions of the terms "linear," branched, "saturated," unsaturated, "unsubstituted and" substituted can in particular correspond to the definitions given above. Similarly, the definitions and / or suitable examples of the terms "alkylene group," heteroalkylene group, rwrinaiizv / lon-Ciri mnp Hpfprnrvrlnalkylpn-Grt innp. ..Arvlen-Gruooe.
"Heteroarylene group," aralkylene group and "alkarylene group, respectively, in particular the definitions given above and / or suitable examples of the terms" alkyl group, "heteroalkyl group," cycloalkyl group "," heterocycloalkyl group "," Aryl group, "heteroaryl group," aralkyl group and "alkaryl group, respectively, respectively, except that the groups represented by L are divalent (bivalent) groups, so
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- 23 as indicated by their ending (or suffix) "-en". Likewise, the definitions and / or suitable examples of the terms "alkyl group," heteroalkyl group, "cycloalkyl group," heterocycloalkyl group, "aryl group," heteroaryl group, "aralkyl group and" alkaryl group, may be the are represented by X, in particular correspond to the definitions given above, except that the groups represented by X are z-valued groups.
The “silicon-containing divalent group and / or the“ silicon-containing z-valent group ”can in particular comprise groups which contain one or more silicon (Si) atoms and optionally furthermore one or more of, for example, C-, 0-, N, P and / or H atoms. Suitable examples thereof include an Si atom, - [(Si-alkyl),] - (such as - [(Si-CH ₂ ),]), - [(Si-O),] - and - [(Si N), ·] -.
In one embodiment, Z may independently represent hydrogen on each occurrence or may represent a thiol protecting group selected from the group consisting of: an acyl group, a silyl group, and a siloxal group.
In one embodiment, independently of each occurrence, L may represent a single bond or a divalent group selected from the group consisting of: a linear or branched, saturated or unsaturated alkylene group having from 1 to 18 carbon atoms and is optionally substituted with one or more hydroxyl groups, - (CO) O-, -O (CO) -, a linear or branched, saturated or unsaturated, divalent alkyl ester group which has from 1 to 18 carbon atoms, a linear or branched, saturated or unsaturated, substituted or unsubstituted acylene group which has from 1 to 20 carbon atoms, a linear or branched, substituted or unsubstituted alkoxylene group which has from 1 to 8 carbon atoms, a saturated or unsaturated, substituted or unsubstituted cycloalkylene Group having from 3 to 12 carbon atoms r substituted or unsubstituted arylene group having from 6 to 16 carbon atoms, or a linear or branched, saturated
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24 or unsaturated alkylene group which has from 2 to 20 carbon atoms and is interspersed (or inserted at intervals) by one or more of oxygen, sulfur, a substituted or unsubstituted imine group, - (CO) -, -O (CO) -, - (CO) O-, -O (CO) O-, - (NR ₁₀ ) (CO) O5 and / or -0 (CO) (NRio) -, whereby Rio - independently of each other with each occurrence
represents one of the following: a hydrogen atom, a linear or branched, saturated or unsaturated, substituted or unsubstituted alkyl group, a linear or branched, saturated or unsaturated, substituted or unsubstituted heteroalkyl group, a saturated or unsaturated, substituted or unsubstituted cycloalkyl group , a saturated or unsaturated, substituted or unsubstituted heterocycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a linear or branched, substituted or unsubstituted aralkyl group, or a linear or branched, substituted or unsubstituted Alkaryl group.
In one embodiment, X may represent a z-valent group selected from the group consisting of: a linear or branched, saturated or unsaturated alkyl group having from 1 to 18 carbon atoms 20 and optionally substituted with one or a plurality of hydroxyl groups, a linear or branched, saturated or unsaturated, z-valent alkyl ester group which has from 1 to 18 carbon atoms, a linear or branched, saturated or unsaturated, substituted or unsubstituted acyl group, from 1 to 20 Having carbon atoms, a linear or branched, substituted or unsubstituted alkoxy group having from 1 to 8 carbon atoms, a saturated or unsaturated, substituted or unsubstituted cycloalkyl group having from 3 to 12 carbon atoms, a substituted or unsubstituted arylene Group having from 6 to 16 carbon atoms the linear or branched or cyclic group of any of the following: a Si atom, - [(Si-alkyl) z] - (such as - [(Si-CH ₂ ) ₂ ] -), - [(Si-O) _z ] ~ or - [(Si-N) J-, where the group is substituted z times by -L-SH, or a linear or branched, saturated or unsaturated alkyl group which has from 2 to 20 carbon atoms and is interspersed with one or more of the following: oxygen, 35 sulfur, a substituted or unsubstituted imine group, - (CO) -, -O (CO) 25/66
- 25, - (CO) O-, -O (CO) O-, - (NRio) (CO) 0- and / or -O (CO) (NRi ₀ ) -, where Rio is as defined above.
In one embodiment, the at least one chemical compound C2 can have the following: at least two functional thiol groups and at least one, in particular at least two, functional groups which are selected from the group consisting of: a silane (an Si atom), a siloxane (-Si-O-), a carbonate, a carbamate, an ether and an ester. In particular, the number of functional thiol groups and the number of functional groups selected from the group consisting of a carbonate, a carbamate, an ether and an ester may be the same or different in the at least one chemical compound C2 . For example, the number of functional thiol groups and / or the number of functional groups selected from the group consisting of a carbonate, a carbamate, an ether and an ester can be as follows: 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 25, 30, 35, 40, 45, 50 or more and / or 1000, 900, 800, 750, 700, 650, 600, 550, 500, 450, 400, 350, 300, 275, 250, 225, 200, 190, 180, 170, 160, 150, 140, 130, 125, 120, 115, 110, 105, 100, 95, 90, 85, 80, 75, 70, 65, 60, 55, 50, 45, 40, 38, 36, 35, 34, 33, 32, 31, 30, 29, 28, 27, 26, 25, 24, 23, 22, 21, 20, 19, 18, 17, 16, 15, 14, 13, 12, 11, 10, 9, 8, 7, 6, 5, 4, 3 or less.
Suitable examples of the at least one chemical compound C2 include, for example, the following compounds:
HS
HS
SH / 66
- 26 trimethylpropane tri (3-mercaptopropionate) (TMPMP)
i
THIO-1
THIO-2
THIO-3
THIO-4

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- 27 10

Further suitable examples of the at least one chemical compound C2 are shown on pages 23 and 24 of WO 2013/052328 A1, the disclosure of which is incorporated herein by reference.
In one embodiment, the ratio of the number of terminating alkyne functional groups to the number of thiol functional groups in the resin compound can be from 1: 1.8 to 1: 2.25, in particular from 1: 1.85 to 1: 2.2 , in particular from 1: 1.88 to 1: 2.15, in particular from 1: 1.9 to 1: 2.1, in particular from 1: 1.95 to 1: 2.05, in particular approximately 1: 2. If the ratio of the number of the terminal functional alkyne groups to the number of the functional thiol groups in the resin compound is within the above ranges, the number of the residual ones (after completion
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- 28 of the thiol-yn reaction) reactive groups and the number of residual (after completion of the thiol-yn reaction) monomers in the polymer formed, which can be advantageous, especially if the polymer (or an article that Includes polymer or is formed from this) is used in medical or biomedical applications.
In one embodiment, the number of final functional alkyne groups to the number of functional thiol groups can be less than 1: 2, for example from 1: 2.01 to 1: 2.3, in particular from 1: 2.05 to 1: 2 , 25, in particular from 1: 2.1 to 1: 2.2. If the ratio of the number of terminal alkyne functional groups to the number of thiol functional groups in the resin compound is within the above ranges, then some thiol functional groups may remain in the polymer formed after completion of the thiol-yn reaction, particularly upon the surface of the polymer or article comprising or being formed from the polymer. Thereby, a surface-modified polymer or a surface-modified article can be obtained. In particular, such residual or residual functional thiol groups can serve as an anchor or coupling site (binding site) capable of coupling the polymer or article with an additive such as an organic filler (e.g. heparin) and / or an inorganic one Filler. Binding (coupling) of the remaining or residual functional thiol group with an additive can be carried out, for example, by means of a thiol-ene reaction, such as a thiol-Michael addition, which are typically catalyzed under basic conditions. Binding (coupling) the remaining or residual functional thiol groups with an additive can also involve the formation of disulfide bonds (disulfide bridges), particularly in the event that a protein or a peptide is coupled to the polymer or article should. As a result, the polymer or article can be given additional advantageous physiological properties, for example anticoagulant (or (blood) anticoagulant) properties in the case of heparin.
The at least one chemical compound CI can be contained in the resin compound in an amount of 10 to 90% by weight, in particular 15 to 85% by weight, in particular 20 to 80% by weight, in particular 25 to 75% by weight .
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29%, in particular of, for example, from 20 to 70% by weight, from 25 to 65% by weight, from 30 to 60% by weight, from 35 to 55% by weight, from 38 to 52% by weight .-% or from 40 to 50 wt .-%.
The at least one chemical compound C2 can be contained in the resin compound in an amount of 10 to 90% by weight, in particular 15 to 85% by weight, in particular 20 to 80% by weight, in particular 25 to 75% by weight . ° / o, in particular of, such as from 20 to 70% by weight, from 25 to 65% by weight, from 30 to 60% by weight, from 35 to 55% by weight, from 38 to 52 % By weight or from 40 to 50% by weight.
In one embodiment, the resin compound may further comprise at least one initiator selected from the group consisting of a photoinitiator and a thermal initiator. The presence of at least one initiator in the resin compound can help initiate the reaction between the yn compound and the thiol compound in a thiol-yn reaction. Thus, the presence of the at least one initiator can increase the rate of polymerization (rapidity) and / or reduce the curing (or drying out) time. As a result, the presence of the at least one initiator is particularly advantageous when the resin compound is used as or in an ink for a printing process, particularly in a three-dimensional printing process, where typically the object to be printed is formed layer by layer, which requires that the previous one Layer is substantially hardened or cured before the subsequent layer is formed. In addition, by using a photoinitiator and / or a thermal initiator, the thiol-yn reaction can be selectively controlled, particularly with respect to a particular location or area from or within the resin compound where the polymerization is to be initiated / promoted, as desired, for example by pointing an appropriate energy source at the particular location or area, thereby enabling the formation of certain high resolution structures as a result of the printing process.
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The term “photoinitiator” as used herein refers in particular to a compound that can be activated by an energy-carrying activation beam (such as electromagnetic radiation), for example by irradiation with the same. When activated by an energy-carrying beam, the photoinitiator can in particular be converted into a radical thereof. Consequently, the photoinitiator can in particular be a radical-generating photoinitiator.
The photoinitiator can in particular be a type I photoinitiator or a type II photoinitiator.
The photoinitiator can in particular be an ultraviolet-active photoinitiator and / or a photoinitiator active in visible light. In other words, the photoinitiator can in particular be a compound which is activated by electromagnetic radiation in the ultraviolet wavelength range (such as the wavelength range from 10 to 380 nm, in particular from 200 to 380 nm), and / or by electromagnetic radiation in the wavelength range from visible light (such as the wavelength range from 380 to 780 nm).
The term "thermal initiator" (or thermal initiator), as used herein, refers in particular to a compound that can be activated by thermal energy, for example by directing thermal energy onto the compound, such as by heating and / or by exposure to electromagnetic radiation in the infrared Wavelength range (such as the wavelength range from 780 nm to 1 mm) and / or in the microwave wavelength range (such as the wavelength range from 1 mm to 300 mm). When activated by thermal energy, the thermal initiator can in particular be converted into a radical of the same. The thermal initiator can thus in particular be a radical-generating thermal initiator.
The photoinitiator and / or the thermal initiator is not particularly limited as long as it can be activated by electromagnetic radiation and / or thermal energy, to thereby initiate the thiol-yn reaction between the yn component and the thiol component in the resin compound.
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In one embodiment, the initiator can be at least one chemical compound which is selected from the group consisting of: a quinone compound, a camphorquinone compound, an azide compound, an azo compound, in particular azobisisobutyronitrile (AIBN) , a peroxide compound, in particular benzoyl peroxide, a disulfide compound, a bisimidazole compound, an alkyl halide, an alkylthiocyanate, a phosphine oxide compound, a substituted or unsubstituted thioxanthone, a substituted or unsubstituted benzophenone, or mixtures thereof. The term "substituted" can in particular correspond to what has been defined above, as long as the substituent does not significantly reduce the reactivity of the initiator. As is well known to those skilled in the art, these chemical compounds can contain radicals and / or residues that have undivided (or not shared) valence electrons or at least one undivided pair of electrons when activated by an energy source, such as irradiation with an energy-carrying activation beam and / or Thermal energy.
A particularly suitable example of an initiator, in particular a photoinitiator, is a mixture of 2-hydroxy-2-methyl-lphenylpropanone and diphenyl-2,4,6-trimethylbenzoylphosphine oxide, in particular a 50% by weight / 50% by weight Mixture thereof. In particular, camphorquinone can be particularly advantageous with regard to its high biocompatibility.
Further suitable examples of initiators, both photoinitiators and thermal initiators, are given on pages 17 to 20 of WO 2013/052328 A1, the disclosure of which is incorporated herein by reference.
The content of the at least one initiator can be in particular from 0.1 to 20% by weight, such as from 0.2 to 15% by weight, in particular from 0.5 to 12.5% by weight, in particular from 1 to 10% by weight, especially 2 to 8% by weight, in terms of the total weight of the resin compound.
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In one embodiment, the resin compound may further comprise at least one additive selected from the group consisting of a pigment, an inorganic filler, an organic filler and a stabilizer. By the presence of an additive such as a pigment, an inorganic filler and / or an organic filler, the products obtained by the thiolyn reaction, for example the products of a printing process using the resin compound, can be customized with additional specific ones advantageous properties, as may be desired. The presence of a stabilizer in the resin compound can be helpful to avoid premature initiation of the thiol-yn reaction between the yn component and the thiol component. Accordingly, the presence of the at least one stabilizer can improve the storage (or bearing) properties of the resin compound.
The pigment can be an organic or an inorganic pigment. The pigment is not particularly limited, and any pigment usually used for printing, for example, can be used as long as it does not significantly interfere with the thiol-yn reaction between the yn component and the thiol component in the resin compound.
Suitable examples of pigments are disclosed, for example, in paragraphs [0128] to [0138] of WO 2008/074548, column 14, line 39 to column 15, line 46 of US 6,045,607, pages 12 to 16 of WO 2005/049744, the provides additional references, the disclosures of all of which are incorporated herein by reference. The pigment can be surface treated to improve its dispersibility in the resin compound.
The inorganic filler is not particularly limited as long as it controls the thiol-yn reaction between the yn component and the thiol component in the
Resin compound not significantly affected. In particular, the inorganic filler can be any of a calcium carbonate, a calcium phosphate and / or a hydroxyapatite, which are particularly suitable when the product obtained after the thiol-yn reaction is used, for example by a printing process, as an implant, a bone substitute and / or a dental product, such as a denture.
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- 33 Further suitable examples of inorganic fillers are disclosed on pages 24 to 27 of WO 2013/052328 A1, the disclosure of which is incorporated herein by reference.
The organic filler is not particularly limited as long as it does not significantly affect the thiol-yn reaction between the yn component and the thiol component in the resin compound. In particular, the organic filler can be a heparin, a collagen and / or a gel (or gelatin), which are particularly suitable when the product obtained after the thiol-yn reaction is used as an implant, for example by a printing process Bone replacement and / or a dental product, such as a denture. In addition, the organic filler may include physiologically active compounds such as proteins, peptides, antibodies, drugs and the like.
Further suitable examples of organic fillers are disclosed on pages 24 to 27 of WO 2013/052328 A1 and the paragraph bridging pages 7 and 8 of WO 2012/103445 A2, the disclosures of which are incorporated herein by reference.
The stabilizer can in particular be a polymerization inhibitor and can in particular be helpful in order to prevent premature initiation and / or spreading of the thiol-yn reaction between the yn component and the thiol component. In particular, the stabilizer may comprise any one or more selected from the group consisting of: a phenolic antioxidant, a phosphorus-containing compound, a hydroquinone such as hydroquinone monomethyl ether (HQME), a hydroxylamine and a sterically hindered amine. In particular, the stabilizer can be a hydroquinone, t-butyl catechol, pyrogallol or an ether thereof, butyl hydroxytoluene (BHT, 2,6-di-tert-butyl-4-methylphenol) and / or butylated hydroxyanisole (BHA, 2-tert-butyl- 4-hydroxyanisole and / or 3-tert-butyl-4-hydroxyanisole).
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Suitable commercial stabilizers are, for example, Sumilizer ™ GA-80, Sumilizer ™ GM and Sumilizer ^rN GS available from Sumitomo Chemical Co. Ltd., Genorad ™ 16, Genorad ™ 18 and Genorad ™ 20 available from Rahn AG, Irgastab ™ UV22 available from BASF SE, Additol ™ S (S100, S110, S120 and S130) available from Cytec Surface Specialties.
Because excessive addition of these stabilizers or polymerization inhibitors can slow down the curing rate, it is preferred that the amount capable of preventing polymerization be determined before mixing. The amount of a polymerization inhibitor is preferably less than 5% by weight, more preferably less than 3% by weight of the total resin compound.
The content of the at least one additive selected from the group consisting of a pigment, an inorganic filler, an organic filler and a stabilizer, in particular its total content, can be in particular from 0.1 to 60% by weight, such as about from 0.2 to 50% by weight, in particular from 0.5 to 40% by weight, in particular from 1 to 30% by weight, in particular from 2 to 20% by weight, based on the total weight of the Resin compound.
Further chemical compounds or constituents can be contained in the resin compound.
For example, other monomers different from the yn and thiol monomers described above, for example vinyl-functionalized monomers, can be contained in the resin compound, which in particular can copolymerize with the yn and / or thiol monomer and which can thereby impart further specific properties the (co) polymer obtained by polymerizing some or all of the components of the resin compound. Suitable examples of vinyl-functionalized monomers are disclosed, for example, in paragraphs [0025] to [0037] of WO 2013/052328 A1, the disclosure of which is incorporated herein by reference.
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- 35 Furthermore, dispersants, wetting agents and / or sequestering agents (or complexing agents) (chelating agents) can be contained in the resin compound.
In particular, the resin compound may further contain surfactants which are suitable as dispersing agents and / or wetting agents, such as anionic surfactants, cationic surfactants, nonionic surfactants and / or ampholytic surfactants.
Suitable examples of anionic surfactants include surfactants which include the following: carboxylate, sulfate, phosphate and / or sulfonate groups, e.g. amino acid derivatives, fatty alcohol ether sulfates, fatty alcohol sulfates, soaps (such as sodium soaps and / or potassium soaps), alkylphenol ethoxylates , fatty alcohol ethoxylates, alkyl sulfates, olefin sulfates and / or alkyl phosphates.
Suitable examples of cationic surfactants include quaternary ammonium or quaternary phosphonium compounds, for example tetraalkylammonium salts, N, N-dialkylimidazoline compounds, dimethyldistearylammonium compounds, N-alkylpyridine compounds, and / or ammonium chlorides.
Suitable examples of non-ionic surfactants include ethoxylates, for example ethoxylated addition products of alcohols such as polyoxyalkylene polyols, amines, fatty acids, alkylphenols, ethanolamides, polysiloxanes and / or fatty acid esters, alkyl or alkylphenylpolyglycol ethers such as fatty acid alcohols or fatty alcohol amides or fatty alcohols. Alkyl glycosides, sugar esters, sorbitan esters, polysorbates and / or trialkylamine oxides, esters and / or amides of poly (meth) acrylic acids with polyalkylene glycols and / or aminopolyalkylene glycols, each of which can be terminated by alkyl groups on one side.
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36 Suitable examples of ampholytic surfactants include amphoteric electrolytes, also called ampholytes, such as aminocarboxylic acids and / or betaines,
Suitable conventional examples include Tego Wet and / or the Glide from Evonik Industries, Byk 016, 348, UV3500, 9151 from Altana AG, Edaplan 710, 711, 910, 915 from Münzing Chemie GmbH.
Further suitable examples of additional compounds or ingredients, in particular dispersing agents and surface-active substances, are disclosed on pages 34 to 37 of WO 2013/087427 A1, the disclosure of which is incorporated herein by reference.
The resin compound can be solid, semi-solid (mushy) or liquid. Because the monomer and / or the thiol monomer are typically liquid, the resin compound can be, in particular, a solution, an emulsion or a dispersion (in particular a solid-liquid dispersion, such as a suspension). In particular, the resin compound does not form a hydrogel or any other gel-like form. In particular, the resin compound is not a hydrogel before the thiol-yn reaction (before the polymerization / curing) nor after the thiol-yn reaction (after the polymerization / curing). Instead, a polymer, in particular a solid or semi-solid (pulpy) polymer, is formed after the thiol-yn reaction (after the polymerization / curing).
In particular, the resin compound can be substantially solvent-free, such as substantially water-free. The expression “essentially solvent-free, as used herein, can particularly mean that the resin compound does not contain more than 15% by weight of a solvent, in particular not more than 10% by weight, in particular not more than 5% by weight, in particular contains not more than 2% by weight, in particular not more than 1% by weight.
Accordingly, the resin compound may contain substantially no solvent such as a polar solvent or a non-polar solvent such as water, an alcoholic solvent (such as methanol,
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- 37 ethanol, glycol, 1-propanol, 2-propanol (IPA), propylene glycol, 1-butanol, 2-butanol, isobutyl alcohol, butylene glycol and the like), an ether solvent (such as dimethyl ether, diethyl ether, tert-butyl methyl ether, 1.4 -Dioxane, tetrahydrofuran (THF) and the like), an ester solvent (such as ethyl acetate and the like), a carbonate solvent (such as dimethyl carbonate, diethyl carbonate and the like), a halogenated alkane solvent (such as dichloromethane, trichloromethane, tetrachloromethane, 1 , 2Dichloroethane and the like), a nitrile solvent (such as acetonitrile and the like), an aldehyde or ketone solvent (such as acetone and the like), an amide solvent (such as dimethylformamide (DMF) and the like), a sulfoxide Solvents (such as dimethyl sulfoxide (DMSO) and the like), an acid solvent (such as formic acid, acetic acid and the like), hydrocarbon solvents (such as pentane, cyclopent an, hexane, cyclohexane, heptane, octane and the like), or an aromatic solvent (such as benzene, toluene and the like).
In one embodiment, the at least one chemical compound CI and the at least one chemical compound C2 can form a (single) chemical compound. In other words, the resin compound can comprise (or consist of) at least one chemical compound C3, which has (i) at least one terminal functional alkyne group, (ii) at least one functional ester group and (iii) at least two functional thiol groups. Groups.
The at least one final functional alkyne group, the at least one functional ester group and / or the at least two functional thiol groups of the chemical compound C3 can in particular be those which have been illustrated above. In addition, the resin compound comprising at least one chemical compound C3 may further comprise further ingredients or compounds as described in detail above, in particular the at least one initiator selected from the group consisting of a photoinitiator and a Thermal initiator, the photo acid, the photobase, the at least one additive selected from the group consisting of a pigment,
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38 an inorganic filler, an organic filler and a stabilizer, the other monomers different from the yn and the thiol monomer, surface-active substances, dispersants, wetting agents and / or sequestering agents.
By comprising at least one chemical compound C3, the resin compound can exhibit particularly advantageous properties such as a high reaction (polymerization) speed (high curing speed), a particularly low content of residual monomers, a particularly small shrinkage of the resulting polymer, excellent mechanical properties Properties (such as modulus of elasticity) of the resulting polymer, and the like.
In a second aspect, the present invention relates to the use of the resin compound according to the present invention as or in an ink which is suitable, for example, in a printing process, as will be described in more detail below. In particular, the resin compound can be used as an ink (a printing ink), i.e. the resin compound itself can be used directly as an ink. Alternatively, the resin compound can be used in an ink (printing ink), i.e. as a component or an ingredient of an ink together with suitable one or more further components or ingredients typically used in an ink.
In a third aspect, the invention relates to a set (kit) comprising:
at least one chemical compound CI, comprising (i) at least one terminal functional alkyne group and (ii) at least one functional ester group, and at least one chemical compound C2 which has at least two functional thiol groups.
The at least one chemical compound CI as well as the at least one chemical compound C2 can in particular be those described above in
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39 details have been described regarding the resin compound according to the present invention.
The chemical compounds CI and C2 can be provided in a spatially separate manner in particular in the set, in particular an equipment of parts (kit-of-parts). In particular, the chemical compounds CI and C2 can be provided in separate chambers of the set. This could be advantageous if the at least one chemical compound CI and / or the at least one chemical compound C2 are reactive to such an extent that both tend to react (prematurely) with the other chemical compound / with one another, themselves when stored in the dark (such as when packaged using a translucent material) and / or at low temperatures (such as a temperature of no more than 10 ° C, especially no more than 5 ° C, such as about no more than 0 ° C).
In particular, any of the chemical compound CI and / or chemical compound C2 chambers, as well as any additional chamber of the set, may contain ingredients or constituents independently, as described above in detail regarding the resin compound of the present invention , in particular the at least one initiator which is selected from the group consisting of a photoinitiator and a thermal initiator, the photo acid, the photobase, the at least one additive which is selected from the group consisting of a pigment, an inorganic filler , an organic filler and a stabilizer, the other monomers different from the yn and the thiol monomer, surfactants, dispersants, wetting agents and / or sequestering agents.
In particular, the set can be a two, three, four or more component system, such as a 2K system, a 3K system, a 4K system and the like.
Before use, for example in a printing process, the components contained in separate chambers of the set are mixed.
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- 40 Mixing can be carried out manually or (semi) automatically by a suitable device or a dispenser. The components contained in the separate chambers of the set can in particular not more than 48 hours, not more than 24 hours, not more than 12 hours, not more than 6 hours, not more than 4 hours, not more than 3 hours, not more than 2 hours, no more than 90 minutes, no more than 60 minutes, no more than 45 minutes, no more than 30 minutes, no more than 25 minutes, no more than 20 minutes, no more than 15 minutes, no more than 10 minutes , no more than 7.5 minutes, no more than 5 minutes, no more than 4 minutes, no more than 3 minutes, no more than 2 minutes, no more than 90 seconds, no more than 60 seconds, no more than 45 seconds , no more than 30 seconds, no more than 25 seconds, no more than 20 seconds, no more than 15 seconds, no more than 10 seconds, no more than 7.5 seconds, no more than 5 seconds, no more than 4 seconds , no more than 3 seconds, no more than 2 seconds, no more than 1 second ande mixed before use, for example in a printing process.
In a fourth aspect, the present invention relates to the use of the kit (k / 't) according to the present invention for preparing a resin compound, in particular the resin compound according to the present invention, suitable for use as or in an ink which for example, in a printing process as described in further detail below. The components contained in the separate chambers of the set can be mixed to prepare the resin compound. Mixing can be done manually or (semi) automatically by a suitable device or dispenser.
In a fifth aspect, the present invention relates to a printing method comprising the following steps:
Providing the resin compound according to the present invention, the resin compound further containing at least one initiator, and
Directing an energy source to at least a portion of the resin compound so that polymerization is effected from the at least a portion of the resin compound and so that a polymer is obtained.
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- 41 In one embodiment, the printing process can be a two-dimensional printing process and the resin compound can be provided on a substrate.
The term “two-dimensional printing process, as used herein, in particular means that the product of the printing process extends in two directions (for example length and width), but not in a third direction (for example height). As a result, the product of a two-dimensional printing process can be substantially flat or sheet-like.
The two-dimensional printing process can in particular be an ink jet printing process or a laser printing process.
The substrate can be flexible, but it can also have a certain stiffness or be stiff as desired. The material of the substrate is not particularly limited and various suitable materials are known to the person skilled in the art. In particular, the substrate can be paper or another cellulose-based material that is suitable for printing. Other suitable substrate materials include polyesters, polysulfones, polyarylates, polyacrylates, polycyclic olefins, polyimides, glass, or combinations or compositions thereof. By way of example only, further substrate materials include polyesters, such as polyethylene terephthalate (PET), polyethylene naphthalates (PEN), polycarbonates (PC), polysulfones, such as polyethersulfone (PES), polyarylates (PAR), polycyclic olefins (PCO), polyimides (PI ), Polyolefins, such as polyethylene (PE), polypropylene (PP), vinyl polymers, such as polystyrene (PS), polyvinyl chloride (PVC), polymethyl methacrylate (PMMA), polyamides, polyethers, polyketones, such as aromatic polyether ketones (e.g. PEEK), Polysulfides (e.g. PPS), fluoropolymers such as polyvinylidene fluoride (PVDF), polytetrafluoroethylene (such as PTFE), fluorinated ethylene propylene (FEP), liquid crystal polymers, polyepoxides, polyurethanes, polysiloxanes (e.g. PDMS), biopolymers or combinations, copolymers, compositions and / or Mixtures thereof, especially compositions or laminates thereof, with paper or any cellulose-based material suitable for printing.
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- 42 In one embodiment, the printing process can be a three-dimensional printing process.
The term “three-dimensional printing process, as used herein, means in particular that the product of the printing process extends in three directions (for example length, width and height). Consequently, the product of a three-dimensional printing method can in particular be a three-dimensional object.
The three-dimensional printing process can in particular be one selected from the group consisting of: stereolithography (SLA), two-photon absorption (TPA) polymerization, digital light processing (DLP, digital light processing), solid ground curing (SGC) and Multi-jet modeling (MJM). Stereolithography (SLA) may be preferred for its high resolution.
In the step of providing the resin compound, the resin compound further comprises an initiator, in particular a photoinitiator and / or a thermal initiator. The initiator can be, in particular, what has been defined above in detail with respect to the resin compound according to the present invention.
In the step of directing an energy source to at least a part of the resin compound (curing step), a thiol-yn reaction can be effected in the at least part of the resin compound to which the energy source has been directed, with the result that the yn component and the thiol component undergoes a crosslinking (polymerization) reaction in this part, and thus a polymer is formed in that part of the resin compound to which the energy source has been directed.
In particular, the energy source can be directed to the at least a portion of the resin compound in a controlled manner, particularly controlled by a computer system, to form a desired pattern or structure of the resulting polymer.
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- 43 The expression "at least a part of the resin compound" can in particular mean that not 100% of the resin compound are exposed to the energy source. In particular, the expression “at least part of the resin compound can mean that at least 5%, in particular at least 10%, in particular at least 15%, in particular at least 20%, in particular at least 25%, in particular at least 30%, in particular at least 35%, in particular at least 40 %, in particular at least 45%, in particular at least 50%, in particular at least 55%, in particular at least 60%, in particular at least 65%, in particular at least 70%, in particular at least 75%, in particular at least 80% of the resin compound are exposed to the energy source, and he can mean that in particular not more than 95%, in particular not more than 90%, in particular not more than 85%, in particular not more than 80%, in particular not more than 75%, in particular not more than 70%, in particular not more than 65%, especially not more than 60%, especially not more than 55%, especially not more than 50%, especially not more than 45%, especially not more a When 40%, in particular not more than 35%, in particular not more than 30%, in particular not more than 25%, in particular not more than 20%, the resin compound is exposed to the energy source.
It may be advantageous to perform the step of directing an energy source at least a portion of the resin compound under an inert gas (or inert gas) atmosphere (such as under a N , CO Or a rare gas, especially Ar, atmosphere), wherein it it is also possible to carry out this step under an ambient gas atmosphere, such as air, or even under (essentially) pure oxygen with regard to the intensity of the thiol-yn reaction to oxygen.
The duration of the step of directing an energy source to at least a part of the resin compound is not particularly limited, and can be appropriately selected by a person skilled in the art, depending in particular on the type of printing process and the constituents of the resin compound (especially its reactivity). For example, suitable times
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- 44 (time periods) for directing an energy source from 1 ms to 1 h, in particular from 1 s to 1 min.
The intensity of directing an energy source is not particularly limited and can be appropriately selected by a person skilled in the art, depending in particular on the type of printing process, the constituents of the resin compound and the duration of the step. In particular, the intensity can be from 0.01 to 20 W / cm ² , in particular from 0.1 to 5 W / cm ² .
In one embodiment, the step of directing an energy source may include at least a portion of the resin compound or may be followed by a step of post-curing, wherein energy (from an energy source) continues to be supplied to the initially formed polymer. For example, in the case of stereolithography, the (initially) formed polymer can be irradiated further or again with ultraviolet radiation in a post-curing step.
In one embodiment, the at least one initiator may include at least one photoinitiator, and the step of directing an energy source onto at least a portion of the resin compound may include irradiating the at least a portion of the resin compound with an energizing activation beam.
The energy-carrying activation beam can in particular have electromagnetic radiation (in particular actinic (or photochemically active) radiation).
In particular, the energy-carrying activation beam can be at least one selected from the group consisting of: ultraviolet radiation (such as having a wavelength from 10 to 380 nm, in particular from 200 to 380 nm, in particular from 250 to 380 nm), radiation visible light (such as having a wavelength of 380 to 780 nm), infrared radiation (such as having a wavelength of 780 nm to 1 mm, in particular near infrared radiation having a wavelength of 780 nm to 1.4 μm), microwave radiation (such as having a Wavelength from 1 to 300 mm),
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45 gamma radiation (such as having a wavelength of 0.1 to 5 pm), an X-ray (such as having a wavelength of 1 pm to 10 nm) or an electron beam (such as beta radiation).
In one embodiment, the at least one initiator may include at least one thermal initiator, and the step of directing an energy source to at least a portion of the resin compound may include directing thermal energy to the at least a portion of the resin compound.
The thermal energy can be directed to the at least part of the resin compound by specifically heating this part of the resin compound, such as by contact heating. The thermal energy can also be directed directly to the at least part of the resin compound by irradiating the at least part of the resin compound with an energy-carrying activation beam which causes a (local) increase in temperature on and / or in the irradiated part of the resin compound, such as infrared radiation and / or microwave radiation.
In particular, the printing process can be a solvent-free printing process. In particular, those solvents as described in detail above regarding the resin compound according to the present invention are preferably not used in the printing process.
In a sixth aspect, the present invention relates to a polymer obtainable by the printing method according to the present invention. The polymer can not only be defined by the constituents of the resin compound, but it can also be defined by the specific pattern and / or the (three-dimensional) study obtained through the printing process. The chemical structure of the polymer can depend in particular on the constituents of the resin compound, but also on the specific conditions of the printing process, which can influence the degree of (cross) crosslinking within the polymer, whereas the geometric structure of the polymer in particular on the specific conditions of the Printing process may depend, such as the specific pattern and / or the (three-dimensional) structure that the polymer through the printing process
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- 46 has been awarded, but also by the components of the resin compound, particularly with regard to the flexibility / strength of the polymer.
In a seventh aspect, the present invention relates to an article which comprises or is formed from the polymer according to the present invention. The article may be made of the polymer with or without any other modifications, such as reshaping, or the article may comprise the polymer in addition to other ingredients or ingredients as desired for specific purposes. The article can also be formed from the polymer.
In one embodiment, the article can be a medical device or a biomedical device. The medical and / or biomedical device can in particular be selected from the group consisting of: an implant, a bone replacement, a tissue replacement and a dental product.
Because a medical and / or biomedical device is typically exposed to a human or animal body in use, the article should preferably be biocompatible. In particular, the article should not significantly interfere with the physiological functions and properties of the part of a human or animal body that is intended to be in contact with the article. In addition, the article should not release any harmful components or any other harmful components in the part of a human or animal body that is intended to be in contact with the article. Because the polymer and consequently the article is obtained as a result of a thiol-yn reaction, the polymer has a very low residual monomer content and low shrinkage, so that the polymer, like the article, is not only highly biocompatible, but is also particularly suitable as a medical or biomedical device.
In one embodiment, the article (as well as the polymer) can in particular be biodegradable.
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47 The expression “essentially” as used herein denotes in particular at least 50%, in particular at least 60%, in particular at least 70%, in particular at least 75%, in particular at least 80%, in particular at least 85%, in particular at least 90%, in particular at least 92.5%, in particular at least 95%, in particular at least 96%, in particular at least 97%, in particular at least 98%, in particular at least 99%, in particular up to 100%, except where specifically stated otherwise.
As explained above, a functional ester group can be hydrolyzed relatively easily (e.g. enzymatically) under a physiological environment, and consequently a product (such as the polymer and / or the article) obtained from a resin compound is wherein the at least one chemical compound CI comprises a functional ester group, is essentially biodegradable and is therefore particularly suitable as an implant, a bone substitute and / or a tissue substitute, which are often intended to grow over time (or gradually) decompose and be replaced by a natural physiological material. Thus, an essentially biodegradable article (or polymer) can in particular be derived from a resin compound which comprises at least one chemical compound CI which has a functional ester group. In addition, an essentially biodegradable article (or polymer) can be particularly suitable as an implant, a bone replacement and / or a tissue replacement.
It may also be advantageous that the product (such as the polymer and / or the article) is at least partially biodegradable and at least partially non-biodegradable, for example when certain persistent mechanical support is desired, or that part of the product is relative biodegrades rapidly, whereas part of the product biodegrades relatively slowly, which can be particularly advantageous if the product is used as an implant, a bone substitute and / or a tissue substitute. Products of this type can in particular be derived from a resin compound which comprises combinations of the chemical compounds CI and C2 which contain non-degradable thiols.
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In an eighth aspect, the present invention relates to the use of the polymer or article according to the present invention in a medical or biomedical application.
In particular, the medical application includes any one selected from the group consisting of implantation, bone insertion or replacement, tissue insertion or replacement, and dental application.
The present invention is further described by the following examples, which are only for the purpose of illustrating specific embodiments, and which are not to be construed in any way as limiting the scope.
Examples
example 1
The maximum reaction rate of the different types of monomers was evaluated using Photo Differential Scanning Calorimetry (Photo-DSC). 8 mg of the corresponding test mixtures consisting of yn monomer (as shown in Table 1 below) and thiol monomer (trimethylpropane tri (3 mercaptopropionate), TMPMP) as well as 5% by weight of a photoinitiator mixture (2-hydroxy- 2-methyl-1-phenylpropanone / diphenyl-2,4,6-trimethylbenzoylphosphine oxide, 50% by weight / 50% by weight) was provided. Acrylate and methacrylate without thiol monomer, but together with 5% by weight of the same photoinitiator mixture, were provided as comparative test mixtures. The test mixtures were placed in an aluminum crucible and irradiated with an Omnicure 'lamp at an intensity of 1 W / cm ² at 50 ° C under a nitrogen gas atmosphere to thereby cure the test mixtures.
Table 1 shows the results of the evaluation of the maximum reaction rate for the monomers tested. The times (t _ma x) at
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- 49 Reaching the maximum enthalpy of reaction indicates the reactivity of the photoreactive systems. Figure 1 is a graphical representation of the test results (I also showing the chemical structural formulas of the alkyne monomers tested and the comparative (meth) acrylic monomers.
[Table 1]
Tested monomer tmax [S] 1,4-butanediol dimethacrylate (BMA) * 6.72 1,4-butanediol diacrylate (BA) * 1.80 Succinic acid dipropargylester (SAPE) 2.74 Succinic acid dibut-l-ynylester (SABE) 2.64 y _Cyclopentane-l, 2-dibut-l-ynylester (CPBE) 2.68 Cylohexane-l, 3,5-tripropargyl ester (CHPE) 3.02 Tricarballylic acid tripropargyl ester (TPE) 3.24 * Comparative connections
As a result, the reaction rates of the monomers tested according to the present invention were slightly lower than the reaction rate of a comparative acrylate, but significantly higher than the reaction rate of a comparative methacrylate.
Example 2
The reaction kinetics of the monomers listed in Table 1 were also evaluated using real-time FTIR spectroscopy. 2 μΙ of the liquid to be tested (alkyne monomer, TMPMP and 5 wt .-% photoinitiator, acrylate or methacrylate, respectively, and 5 wt .-% photoinitiator) were placed between two discs of CaF ₂ and positioned within the optical path. The samples were irradiated from a distance of 9 cm using an Omnicure “S1000 (at 40% of their maximum output). Two measurements per second were taken. The total duration of the measurement was 120 seconds.
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- Figure 2 is a graphical representation of the conversion of the alkyne and alkene content, respectively, during the photopolymerization of 1,4-butanediol dimethacrylate, 1,4-butanediol diacrylate, succinic acid dibut-1ynyl ester and succinic acid dipropargyl ester obtained by real-time FTIR measurements.
To illustrate the conversion kinetics in more detail, the peak areas of the alkyne band (at 3280 cm ¹ ) and the alkene band (at 1640 cm ¹ ) of the (meth) acrylates were integrated using the OPUS software from Bruker Corporation. The normalized values thus obtained are shown in FIG. 2.
In addition, the content of alkyne and alkene, respectively, was determined after a reaction time of 2 min, which corresponds to the content of residual monomers in%. The results are shown in Table 2 below.
[Table 2]
Residual monomer content [%]! 26
A ----------- - i - ......................—
1 ³ . 2 ⁴
Monomer
1.4- butanediol dimethacrylate * *
1.4-butanediol diacrylate * i succinic acid dipropargyl ester ί succinic acid dibut-l-ynyl ester: cyclopentane-l, 2-dibut-l-ynyl ester (CPBE) i cylohexane-l, 3,5-tripropargyl ester (CHPE) | Tricarballylic acid tripropargylester (TPE) * Comparative compounds
As can be seen from the results shown in Figure 2, substantially complete conversion of the alkynes was observed after the thiol-yn reaction, which is particularly advantageous in that it results in a low residual monomer content of 5% or less leads, as shown in Table 2. In contrast, in the case of 1,4-butanediol diacrylate, a residual monomer content of 21% was observed even after 2 minutes of irradiation, and in the case of 1,4-butanediol dimethacrylate
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- 51 residual monomer content of as much as 26% observed. It has been shown that the step growth mechanism of the thiol-yn reaction, which has a delayed gelation point, is far advantageous over the chain growth mechanism of the (meth) acrylates. Due to the substantially lower residual monomer content of the polymers obtained by the thiolyn reaction, less migration of monomers is likely to occur when used as a medical or biomedical device, which makes these polymers particularly suitable for use as or in a medical or biomedical Device.
Example 3 (biocompatibility)
The cytotoxicity of various monomers was determined by a certified laboratory using L929 fibroblast cells from mice. As a (toxic) positive control, Triton X 100 was added to the L929 cells at a final concentration of 1% (v / v). Cell culture medium (or cell culture medium) was used as a (non-toxic) negative control.
After the incubation was completed, the residual protein content of the cells was determined. A reduction in the protein content of L929 cells by more than 30%, relative to the negative control, was evaluated as cytotoxic (which corresponds to the toxicological concentration limit). From this, the half maximum effective concentration (ECso), at which 50% of the cells are destroyed, can be calculated.
The results obtained for various monomers are shown in Figures 3, 4, 5 and 6.
Table 3 shows the determined concentration limits as well as the EC 50 values of the monomers tested.
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- 52 [Table 3]
Monomer concentration limit ______ [mM]
1.4-butanediol dimethacrylate * * <0.16
1.4-butanediol diacrylate * <0.16
Succinic acid dipropargylester | 0.4 'Succinic acid dibut-l-ynylester! 1.5 * Comparative connections .....
EC ₅ o [mM]
0.5
As can be seen from the results of the cytotoxicological evaluation, all alkyne monomers tested show a significantly lower cytotoxicity than their corresponding (meth) acrylate analogues. 1,4-butanediol diacrylate as well as 1,4-butanediol dimethacrylate has proven to be particularly cytotoxic. An EC 50 value of these chemical compounds could not be calculated because the toxic concentration was below the detection limit of the measurement method. Among the alkyne monomers tested, succinic acid dibut-l-ynylester in particular showed an excellent low cytotoxicity.
While the present invention has been described in detail by way of specific embodiments and examples, the invention is not so limited, and various changes and modifications are possible without departing from the scope of the invention.

权利要求:
Claims (46)
[1]
PATENT CLAIMS
1. A resin compound, comprising:
at least one chemical compound CI, comprising (i) at least one terminal functional alkyne group and (ii) at least one functional ester group, and at least one chemical compound C2 which has at least two functional thiol groups.
[2]
2. The resin compound according to claim 1, wherein the at least one terminal functional alkyne group is selected from the group consisting of: propargyl, butynyl and pentynyl.
[3]
3. The resin compound according to claim 1 or 2, wherein the at least one chemical compound CI comprises a chemical compound having a functional group selected from the group consisting of a propargyl ester, a butynyl ester and a pentynyl ester.
[4]
4. The resin compound according to one of the preceding claims, wherein the at least one chemical compound CI is represented by one of the following general formulas (I) to (III):

[5]
5. The resin compound according to any one of the preceding claims, wherein the at least one chemical compound CI has a terminal functional alkyne group.
[6]
6. The resin compound according to any one of the preceding claims, wherein the at least one chemical compound CI has at least two terminal functional alkyne groups.
[7]
7. The resin compound according to any one of the preceding claims, wherein at least one of the functional thiol groups comprises a thiol protecting group.
[8]
8. The resin compound according to claim 7, wherein the thiol protecting group is selected from the group consisting of: an acyl group, a silyl group and a siloxyl group.
[9]
9. The resin compound according to claim 7 or 8, wherein the resin compound further comprises at least one photo acid and / or at least one photobase.
[10]
10. The resin compound according to any one of the preceding claims, wherein the at least one chemical compound C2 is represented by the following general formula (XIII):
X-EL-S-ZL (XIII), where z represents an integer from 2 to 1000,
Z - independently of each other on each occurrence - represents hydrogen or a thiol protective group,
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- 55 L - independently at each occurrence - represents one of the following: a single bond or a divalent group selected from the group consisting of: a linear or branched, saturated or unsaturated, substituted or unsubstituted alkylene group, one
5 linear or branched, saturated or unsaturated, substituted or unsubstituted heteroalkyl group, a saturated or unsaturated, substituted or unsubstituted cycloalkylene group, a saturated or unsaturated, substituted or unsubstituted heterocycloalkyl group, a substituted or unsubstituted arylene group, a substituted
10 or unsubstituted heteroarylene group, a linear or branched, substituted or unsubstituted aralkylene group, a linear or branched, substituted or unsubstituted alkarylene group, or a silicon-containing divalent group, and
X represents a z-valued group which is selected from the group which
15 consists of: a linear or branched, saturated or unsaturated, substituted or unsubstituted alkyl group, a linear or branched, saturated or unsaturated, substituted or unsubstituted heteroalkyl group, a saturated or unsaturated, substituted or unsubstituted cycloalkyl group, a saturated or unsaturated,
20 substituted or unsubstituted heterocycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a linear or branched, substituted or unsubstituted aralkyl group, a linear or branched, substituted or unsubstituted alkaryl group, or one
25 silicon-containing z-valent group.
[11]
11. The resin compound according to claim 10, wherein
Z - independently of each occurrence - hydrogen or a thiol protecting group selected from the group consisting of: one
30 represents acyl group, a silyl group and a siloxal group,
L independently of each occurrence represents one of the following: a single bond or a divalent group selected from the group consisting of: a linear or branched, saturated or unsaturated alkylene group having from 1 to 18 carbon atoms 35 and optionally substituted with one or more hydroxyl groups, - (CO) O
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- 56, -O (CO) -, a linear or branched, saturated or unsaturated, divalent alkyl ester group having from 1 to 18 carbon atoms, a linear or branched, saturated or unsaturated, substituted or unsubstituted acylene group, which by Has 1 to 20 carbon atoms, a linear or branched, substituted or unsubstituted alkoxylene group having from 1 to 8 carbon atoms, a saturated or unsaturated, substituted or unsubstituted cycloalkylene group having from 3 to 12 carbon atoms, a substituted or unsubstituted Arylene group, which has from 6 to 16 carbon atoms, or a linear or branched, saturated or unsaturated alkylene group, which has from 2 to 20 carbon atoms and with one or more of oxygen, sulfur, a substituted or unsubstituted imine group, - ( CO) -, -O (CO) -, - (CO) O-, -O (CO) O-, - (NR ₁₀ ) (CO) O and / or -O (CO ) (N Rio) - is enforced, and
X represents a Z-valent group which is selected from the group consisting of: a linear or branched, saturated or unsaturated alkyl group which has from 1 to 18 carbon atoms and is optionally substituted by one or more hydroxyl groups, a linear or branched, saturated or unsaturated, z-valent alkyl ester group having from 1 to 18 carbon atoms, a linear or branched, saturated or unsaturated, substituted or unsubstituted acyl group having from 1 to 20 carbon atoms, a linear or branched, substituted or unsubstituted alkoxy group having from 1 to 8 carbon atoms, a saturated or unsaturated, substituted or unsubstituted cycloalkyl group having from 3 to 12 carbon atoms, a substituted or unsubstituted arylene group having from 6 to Has 16 carbon atoms, one linear or branched or cyclic en group of one of the following: a Si atom, - [(Si-alkyl) J- (such as - [(Si-CFh) /] -), - [(Si-O) z] - or - [( Si-N) J-, where the group is substituted z times by L-SH, or a linear or branched, saturated or unsaturated alkyl group which has from 2 to 20 carbon atoms and is interspersed with one or more of the following: Oxygen, sulfur, a substituted or unsubstituted imine group, - (CO) -, -O (CO) -, - (CO) O, -O (CO) O-, - (NR ₁₀ ) (CO) O- and / or -0 (CO) (NRio) -,
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- 57 where R _{10 represents} - independently of each other on each occurrence - one of the following: a hydrogen atom, a linear or branched, saturated or unsaturated, substituted or unsubstituted alkyl group, a linear or branched, saturated or unsaturated, substituted or unsubstituted heteroalkyl- Group, a saturated or unsaturated, substituted or unsubstituted cycloalkyl group, a saturated or unsaturated, substituted or unsubstituted heterocycloalkyl group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a linear or branched, substituted or unsubstituted group Aralkyl group, or a linear or branched, substituted or unsubstituted alkaryl group.
[12]
12. The resin compound according to any one of the preceding claims, wherein the at least one chemical compound C2 comprises: at least two functional thiol groups and at least one functional group selected from the group consisting of: a silane, a siloxane, one Carbonate, a carbamate, an ether and an ester.
[13]
13. The resin compound according to any one of the preceding claims, wherein the ratio of the number of terminal functional alkyl groups to the number of functional thiol groups is from 1: 1.8 to 1: 2.25, in particular approximately 1: 2 .
[14]
14. The resin compound according to any one of claims 1 to 12, wherein the ratio of the number of final functional alkyne groups to the number of functional thiol groups is less than 1: 2, in particular from 1: 2.01 to 1: 2 , 3rd
[15]
15. The resin compound according to any one of the preceding claims, wherein the compound comprises from 10 to 90 wt .-% of the at least one chemical compound CI.
[16]
16. The resin compound according to any one of the preceding claims, wherein the compound comprises from 10 to 90% by weight of the at least one chemical compound C2.
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[17]
The resin compound according to any one of the preceding claims, wherein the compound further comprises at least one initiator selected from the group consisting of: a photoinitiator and a thermal initiator.
[18]
18. The resin compound according to claim 17, wherein the photoinitiator is a radical-generating photoinitiator and / or the thermal initiator is a radical-generating thermal initiator.
[19]
19. The resin compound according to claim 17 or 18, wherein the photoinitiator is an ultraviolet-active photoinitiator and / or a photoinitiator active for visible light.
[20]
20. The resin compound according to any one of claims 17 to 19, wherein the compound comprises 0.1 to 20% by weight of the at least one initiator.
[21]
21. The resin compound according to any one of the preceding claims, wherein the compound further comprises at least one additive selected from the group consisting of: a pigment, an inorganic filler, an organic filler and a stabilizer.
[22]
22. The resin compound of claim 21, wherein the compound comprises from 0.1 to 60 percent by weight of the at least one additive.
[23]
23. The resin compound of claim 21 or 22, wherein the at least one additive comprises at least one pigment.
[24]
24. The resin compound according to claim 21 or 22, wherein the at least one additive comprises at least one inorganic filler, in particular a calcium carbonate, calcium phosphate and / or hydroxyapatite.
[25]
25. The resin compound according to claim 21 or 22, wherein the at least one additive comprises at least one organic filler, in particular heparin, collagen and / or gelatin.
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[26]
26. The resin compound according to claim 21 or 22, wherein the at least one additive comprises: at least one stabilizer, in particular a polymerization inhibitor, in particular a phenol antioxidant, a phosphorus-containing compound, a hydroquinone such as a hydroquinone monomethyl ether, a hydroxylamine and / or a sterically hindered amine.
[27]
27. The resin compound according to any one of the preceding claims, wherein the compound does not form a hydrogel.
[28]
28. The resin compound according to one of the preceding claims, wherein the compound is essentially solvent-free, in particular essentially water-free.
[29]
29. The chemical compound according to one of the preceding claims, wherein the at least one chemical compound CI and the at least one chemical compound C2 form a chemical compound C3.
[30]
30. Use of a resin compound according to any one of claims 1 to 29 as one or in an ink.
[31]
31. A set, in particular a kit of components, comprising: at least one chemical compound CI, comprising (i) at least one terminal functional alkyne group and (ii) at least one functional ester group, and at least one chemical compound C2, the has at least two functional thiol groups.
[32]
32. Use of a kit according to claim 31 for preparing a resin compound for use as or in an ink.
[33]
33. A printing process that includes the following steps:
The resin compound of any of claims 1 to 29, wherein the resin compound further comprises at least one initiator, and
60/66
60 directing an energy source to at least a portion of the resin compound to cause polymerization of the at least a portion of the resin compound and to obtain a polymer.
[34]
34. The printing method according to claim 33, wherein the printing method is a two-dimensional printing method and the resin compound is provided on a substrate.
[35]
35. The printing method according to claim 33, wherein the printing method is a three-dimensional printing method.
[36]
36. The printing method according to claim 35, wherein the three-dimensional printing method is one selected from the group consisting of: stereolithography (SLA), two-photon absorption (TPA) polymerization, digital light processing (DLP), solid ground Curing (SGC) and Multi-Jet Modeling (MJM).
[37]
37. The printing method according to any one of claims 33 to 36, wherein the at least one initiator comprises at least one photoinitiator, and the step of directing an energy source onto at least a portion of the resin compound comprises irradiating the at least a portion of the resin compound with an energy-carrying activation beam.
[38]
38. The printing method according to claim 37, wherein the energy-carrying activation beam comprises electromagnetic radiation, which is selected in particular from the group consisting of: ultraviolet radiation, radiation of visible light, infrared radiation and microwave radiation.
[39]
39. The printing method of any one of claims 33 to 38, wherein the at least one initiator comprises at least one thermal initiator, and the step of directing an energy source to at least a portion of the resin compound comprises directing thermal energy to the at least a portion of the resin compound.
61/66
[40]
40. The printing process according to any one of claims 33 to 39, wherein the printing process is a solvent-free printing process.
[41]
41. A polymer obtainable by the printing process according to any one of claims 33 to 40.
[42]
42. An article comprising, or formed from, the polymer of claim 41.
[43]
43. The article of claim 42, wherein the article is a medical device or a biomedical device that is particularly selected from the group consisting of: an implant, a bone replacement, a tissue replacement and a dental product.
[44]
44. The article of claim 42 or 43, wherein the article is substantially biodegradable.
[45]
45. Use of a polymer according to claim 41 or an article according to any one of claims 42 to 44 in a medical or biomedical application.
[46]
46. The use of claim 45, wherein the medical or biomedical application comprises one from the group consisting of: an implantation, a bone insertion or replacement, a tissue insertion or replacement, and a dental application.

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同族专利:

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公开号 | 公开日

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GB201518033D0|2015-11-25|

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WO2017064145A1|2017-04-20|

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法律状态:
2021-05-15| REJ| Rejection|Effective date: 20210515 |

优先权:

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申请号 | 申请日 | 专利标题

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GBGB1518033.4A|GB201518033D0|2015-10-12|2015-10-12|Printable ester based resin compositions and printing method utilizing the same|

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PCT/EP2016/074514|WO2017064145A1|2015-10-12|2016-10-12|Printable ester based resin compositions and printing method utilizing the same|

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