Patent Grant
11471566
The present invention relates to an implant comprising composite powder containing calcium salt obtained by selective laser sintering, especially to implants for use in the field of neuro, oral, maxillary, facial, ear, nose and throat surgery as well as hand, foot, thorax, costal and shoulder surgery.
The invention does not relate to the preparation of the starting material for the implant, nor to the use for purposes other than the production of an implant, especially one that is prepared for use in the field of neuro, oral, maxillary, facial, ear, nose and throat surgery as well as hand, foot, thorax, costal and shoulder surgery.
Calcium carbonate, CaCO3, is a calcium salt of the carbonic acid which today is in use in various fields of daily life. It is used especially as an additive or modifier in paper, dyes, plastics, inks, adhesives and pharmaceuticals. In plastics, calcium carbonate preferentially serves as filler to replace the comparatively expensive polymer.
Also, composite materials are known already and denote a material consisting of two or more bonded materials which has material properties other than its individual components. Concerning the properties of the composite materials, the material properties and the geometry of the components are important. In particular, effects of size frequently play a role. The bonding is usually made by adhesion or form closure or by a combination of both.
Further, also microstructured composite particles containing calcium salts, especially calcium carbonate, are known per se already.
For example, WO 2012/126600 A2 discloses microstructured composite particles obtainable by a method in which large particles are bonded to small particles, wherein
Further, WO 2012/126600 A2 describes microstructured composite particles obtainable by a method in which large particles are connected to small particles, wherein
The composite particles shown in WO 2012/126600 A2 are intended to be suited mainly as an additive, especially as a polymer additive, as an admixture or starting material for the production of components, for use in medical engineering and/or in microtechnology and/or for the production of foamed objects. The method of selective laser sintering (SLM method) is mentioned inter alia in the document.
However, for selective laser sintering more properly suited materials are desired. One drawback of the composite particles of WO 2012/126600 A2 especially is the poor flowability thereof which can only partially be reduced even when flowing aids are used. Additions of said flowing aids are not beneficial, above all, to the production of implants, as they usually have a detrimental effect on the properties of the resulting implant, especially on its biocompatibility and biodegradability. Further, transportation to the laser sintering plant is impeded by the poor flowability.
When producing components by laser sintering making use of the materials of WO 2012/126600 A2, the following additional problems will arise. Although ground composite particles can be sintered, the surface quality and surface finish as well as the component density of the resulting components are not fully satisfactory. Especially better shrinking behavior and better dimensional stability of the resulting components as well as better heat conductivity outside the laser-treated area would be desirable. Moreover, a more efficient production process of components would be desirable. In particular, an enhancement for implants, especially for the field of neuro, oral, maxillary, facial, ear, nose and throat surgery as well as of hand, foot, thorax, costal and shoulder surgery would be desirable.
Against this background, it is the object of the present invention to make available a better implant than before. Especially a material exhibiting improved laser sintering properties which has especially an improved flowability, during laser sintering enables components of improved surface quality and surface finish as well as improved component density to be produced and shows especially better shrinking behavior and improved dimensional stability of the resulting components as well as better heat conductivity outside the laser-treated area should be used for an implant. In addition, a more efficient production process of such implants is requested.
The present disclosure is illustrated by way of example, and not by way of limitation, in the figures of the accompanying drawings and in which like reference numerals refer to similar elements and in which:
This object as well as further objects which are not concretized but can be directly derived from the foregoing context are achieved by providing an implant made from a composite powder including all features of the present claim 1. The subclaims related back to claim 1 describe especially expedient variants. The use claim relates to an especially expedient application of the composite powder according to the invention for producing an implant, especially for the field of neuro, oral, maxillary, facial, ear, nose and throat surgery as well as of hand, foot, thorax, costal and shoulder surgery. Furthermore, an especially advantageous implant is protected which is obtained by selective laser sintering of a composition containing said composite powder and which is especially configured as an implant for applications in the field of neuro, oral, maxillary, facial, ear, nose and throat surgery as well as of hand, foot, thorax, costal and shoulder surgery.
Providing a composite powder comprising microstructured particles obtainable by a process in which large particles are bonded to small particles, wherein
Moreover, said composite powder allows for more efficient production of implants, especially according to the laser sintering method. The melt flow of the melt obtainable using the composite powder according to the invention is significantly increased (enhanced). The composite powder according to the invention can be better processed especially according to the SLM method, compared to conventional materials, and enables a significantly better layer structure in the SLM method. The components obtainable according to the SLM method using the composite powder according to the invention excel by extremely high quality and, compared to components produced according to the SLM method using conventional materials, show definitely fewer defects, increased component density, preferably higher than 95%, especially higher than 97%, as well as less porosity. At the same time, the content of degradation products in the resulting components is significantly lower and the cell compatibility of the components is extremely high.
The other properties of the implants obtainable in this way are excellent, too. The implants show very good mechanical properties as well as excellent pH stability. At the same time, the biocompatibility of the products is significantly enhanced. Comparable products are not obtainable when using the pure polymers, in particular as respective polymer powders which might be processed according to the SLM method are not known.
It is another advantage of the present invention that the properties of said composite powder, especially the flow properties of the composite powder, can be specifically controlled and adjusted by the input and the properties of the large particles and the small particles, especially by the properties of the calcium salt, above all by the particle size of the calcium salt particles, as well as by the quantity of the calcium salt particles. Moreover, by sizing the composite powder especially the calcium salt content, above all the calcium carbonate content, of the composite powder and the flow properties of the composite powder can be varied and specifically adapted to the respective application.
Especially in combination with polylactide as polymer the following advantages are resulting in accordance with the invention.
Using the said composite powder, degradable implants, having controllable absorption kinetics and adjustable mechanical properties can be produced. Polylactides which are preferably contained in the composite powder are biodegradable polymers on the basis of lactic acid. In the organism polylactides are degraded by hydrolysis. Calcium salts, especially calcium phosphate and calcium carbonate, are mineral materials based on calcium and are degraded in the body by the natural regeneration process of the bone. Calcium carbonate has the particularly advantageous property to buffer the acidic milieu which may be toxic to bone cells when the polylactides are degraded. As compared to calcium phosphate (pH 4), calcium carbonate buffers already at a pH value of about 7, i.e. close to the physiological value of 7.4. The time until complete degradation can be adapted via the length of molecular chains and the chemical composition of the polymer, especially of the polylactide. This is similarly possible for the mechanical properties of the polymer.
Said composite powder may be processed to form implant structures with the aid of the generative production method of Selective Laser Melting (SLM). Here a specific adaptation of the material and the production method to each other and to the medical requirements is possible. The use of the generative production and the accompanying freedom of geometry offers the option to provide the implant with an internal and open pore structure corresponding to the surgeon's requests which ensures continuous supply of the implant. Moreover, generatively individually adapted implants as required for supplying large-area bone defects in the craniofacial area can be quickly and economically manufactured. The advantage of said composition for processing by means of SLM especially resides in the fact that the polymer can be melted by laser radiation at relatively low temperatures, preferably less than 300° C., and the inhibiting calcium carbonate particles remain thermally stable at said temperatures. By customized synthesis of said composite powder, the calcium salt particles, especially the calcium carbonate particles, thus can be homogeneously embedded within the entire volume of the implant in a matrix of polylactide without thermal damage by the laser radiation. The strength of the implant is determined, on the one hand, by the polylactide matrix and, on the other hand, by the morphology of the calcium salt particles, especially the calcium carbonate particles, as well as, of preference, also by the mixing ratio of the components used. The implants furthermore are bioactive, as they actively stimulate the surrounding bone tissue to osteogenesis and replacement of the skeleton structure (implant) via the selection of material and the subsequent coating with a growth-stimulating protein (rhBMP-2).
The substantial benefits of the implants made of said composite powder, generatively produced by means of SLM especially are as follows:
Accordingly, the subject matter of the present invention is a composite powder comprising microstructured particles (composite powder) in an implant, the composite powder being obtainable by a method in which large particles are bonded to small particles.
In the present invention, microstructure refers to the microscopic properties of a material. They include, inter alia, the resolvable fine structure and the structure. In liquids as well as in gases, the latter are not provided. Here the individual atoms or molecules are in a disordered state. Amorphous solids mostly have a structural short-range order in the area of the neighboring atoms but no long-range order. Crystalline solids, on the other hand, have an ordered grid structure not only in the short-range area but also in the long-range area.
Within the scope of the present invention, the large particles comprise at least one polymer which basically is not subject to any further restrictions. However, preferably it is a thermoplastic polymer, appropriately a biopolymer, a rubber, especially natural rubber or synthetic rubber, and/or a polyurethane.
The term “thermoplastic polymer” in this context refers to a plastic which can be (thermoplastically) deformed within a specific temperature range, preferably within the range from 25° C. to 350° C. This operation is reversible, i.e. it can be repeated any time by cooling and reheating to the molten state, unless the so-called thermal decomposition of the material starts by overheating. By this feature, thermoplastic polymers differ from the thermosetting plastics and elastomers.
The term “biopolymer” denotes a material consisting of biogenic raw materials (renewable raw materials) and/or being biodegradable (biogenic and/or biodegradable polymer). This term thus covers bio-based biopolymers which are or are not biodegradable as well as petroleum-based polymers which are biodegradable. Thus, a delimitation is made against the conventional petroleum-based materials and, resp., plastics which are not biodegradable such as e.g. polyethylene (PE), polypropylene (PP) and polyvinylchloride (PVC).
The term “rubber” denotes high-molecular non-crosslinked polymeric material having rubber-elastic properties at room temperature (25° C.). At higher temperatures or under the influence of deforming forces, rubber shows increasingly viscous flow and thus enables to be reformed under appropriate conditions.
Rubber-elastic behavior is characterized by a relatively low shear modulus of rather little temperature dependency. It is caused by changes of entropy. By stretching the rubber-elastic material is forced to adopt a more ordered configuration resulting in a decrease of entropy. After removing force, the polymers therefore return to their original position and the entropy increases again.
The term “polyurethane” (PU, DIN abbreviation: PUR) denotes a plastic or synthetic resin which is formed by the polyaddition reaction of diols or polyols with poly-isocyanates. The urethane group is characteristic of a polyurethane.
Within the scope of the present invention, it is especially preferred to use thermoplastic polymers. Especially suited polymers include the following polymers: acrylonitrile-ethylene-propylene-(diene)-styrene copolymer, acrylonitrile-methacrylate copolymer, acrylonitrile-methyl methacrylate copolymer, acrylonitrile-chlorinated polyethylene-styrene copolymer, acrylonitrile-butadiene-styrene copolymer, acrylonitrile-ethylene-propylene-styrene copolymer, aromatic polyesters, acrylonitrile-styrene-acrylic ester copolymer, butadiene-styrene copolymer, cellulose acetate, cellulose aceto butyrate, cellulose aceto propionate, hydrated cellulose, carboxymethyl cellulose, cellulose nitrate, cellulose propionate, cellulose triacetate, polyvinyl chloride, ethylene-acrylic acid copolymer, ethylene-butyl acrylate copolymer, ethylene-chlorotrifluoroethylene copolymer, ethylene-ethyl acrylate copolymer, ethylene-methacrylate copolymer, ethylene-methacrylic acid copolymer, ethylene-tetrafluoroethylene copolymer, ethylene-vinyl alcohol copolymer, ethylene-butene copolymer, ethyl cellulose, polystyrene, poly fluoroethylene propylene, methyl methacrylate-acrylonitrile-butadiene-styrene copolymer, methyl methacrylate-butadiene-styrene copolymer, methyl cellulose, polyamide 11, polyamide 12, polyamide 46, polyamide 6, polyamide 6-3-T, polyamide 6-terephthalic acid copolymer, polyamide 66, polyamide 69, polyamide 610, polyamide 612, polyamide 6I, polyamide MXD 6, polyamide PDA-T, polyamide, polyaryl ether, polyaryl ether ketone, polyamide imide, polyaryl amide, polyamine bismaleimide, polyarylates, polybutene-1, polybutyl acrylate, polybenzimidazole, polybismaleimide, polyoxadiazo benzimidazole, polybutylene terephthalate, polycarbonate, polychlorotrifluoroethylene, polyethylene, polyester carbonate, polyaryl ether ketone, polyetherether ketone, polyether imide, polyether ketone, polyethylene oxide, polyaryl ether sulfone, polyethylene terephthalate, polyimide, polyisobutylene, polyisocyanurate, polyimide sulfone, polymethacryl imide, polymethacrylate, poly-4-methylpentene-1, polyacetal, polypropylene, polyphenylene oxide, polypropylene oxide, polyphenylene sulfide, polyphenylene sulfone, polystyrene, polysulfone, polytetrafluoroethylene, polyurethane, polyvinyl acetate, polyvinyl alcohol, polyvinyl butyral, polyvinyl chloride, polyvinylidene chloride, polyvinylidene fluoride, polyvinyl fluoride, polyvinyl methyl ether, polyvinyl pyrrolidone, styrene-butadiene copolymer, styrene-isoprene copolymer, styrene-maleic acid anhydride copolymer, styrene-maleic acid anhydride-butadiene copolymer, styrene-methyl methacrylate copolymer, styrene methyl styrene copolymer, styrene-acrylonitrile copolymer, vinyl chloride-ethylene copolymer, vinyl chloride-methacrylate copolymer, vinyl chloride-maleic acid anhydride copolymer, vinyl chloride-maleimide copolymer, vinyl chloride-methyl methacrylate copolymer, vinyl chloride-octyl acrylate copolymer, vinyl chloride-vinyl acetate copolymer, vinyl chloride-vinylidene chloride copolymer and vinyl chloride-vinylidene chloride-acrylonitrile copolymer.
Further, also the use of the following rubbers is especially advantageous: naturally occurring polyisoprene, especially cis-1,4-polyisoprene (natural rubber; NR) and trans-1,4-polyisoprene (gutta-percha), primarily natural rubber; nitrile rubber (copolymer of butadiene and acrylonitrile); poly(acrylonitrile-co-1,3-butadiene; NBR; so-called Buna N-rubber); butadiene rubber (polybutadiene; BR); acrylic rubber (polyacrylic rubber; ACM, ABR); fluorine rubber (FPM); styrene-butadiene rubber (copolymer of styrene and butadiene; SBR); styrene-isoprene-butadiene rubber (copolymer of styrene, isoprene and butadiene; SIBR); polybutadiene; synthetic isoprene rubber (polyisoprene; IR), ethylene-propylene rubber (copolymer of ethylene and propylene; EPM); ethylene-propylene-diene rubber (terpolymer of ethylene, propylene and a diene component; EPDM); butyl rubber (copolymer of isobutylene and isoprene; IIR); ethylene-vinyl acetate rubber (copolymer of ethylene and vinyl acetate; EVM); ethylene-methacrylate rubber (copolymer of ethylene and methacrylate; AEM); epoxy rubber such as polychloromethyl oxirane (epichlorohydrin polymer; CO), ethylene oxide (oxirane)-chloromethyl oxirane (epichlorohydrin polymer; ECO), epichlorohydrin-ethylene oxide-allyl glycidyl ether terpolymer (GECO), epichlorohydrin-allyl glycidyl ether copolymer (GCO) and propylene oxide-allyl glycidyl ether copolymer (GPO); polynorbornene rubber (polymer of bicyclo[2.2.1]hept-2-en (2-norbornene); PNR); polyalkenylene (polymer of cycloolefins); silicone rubber (Q) such as silicone rubber but with methyl substituents at the polymer chain (MQ; e.g. dimethyl polysiloxane), silicone rubber with methyl vinyl and vinyl substituent groups at the polymer chain (VMQ), silicone rubber with phenyl and methyl substituents at the polymer chain (PMQ), silicone rubber with fluorine and methyl groups at the polymer chain (FMQ), silicone rubber with fluorine, methyl and vinyl substituents at the polymer chain (FVMQ); polyurethane rubber; polysulfide rubber; halogen butyl rubber such as bromine butyl rubber (BIIR) and chlorine butyl rubber (CIIR); chlorine polyethylene (CM); chlorine sulfonyl polyethylene (CSM); hydrated nitrile rubber (HNBR); and polyphosphazene.
Especially preferred nitrile rubbers include statistic terpolymers of acrylonitrile, butadiene and a carboxylic acid such as methacrylic acid. In this context, the nitrile rubber preferably comprises the following main components, based on the total weight of the polymer: 15.0 wt.-% to 42.0 wt.-% of acrylonitrile polymer; 1.0 wt.-% to 10.0 wt.-% of carboxylic acid and the remainder is mostly butadiene (e.g. 38.0 wt.-% to 75.0 wt.-%). Typically, the composition is: 20.0 wt.-% to 40.0 wt.-% of acrylonitrile polymer, 3.0 wt.-% to 8.0 wt.-% of carboxylic acid and 40.0 wt.-% to 65.0 wt.-% or 67.0 wt.-% are butadiene. Especially preferred nitrile rubbers include a terpolymer of acrylonitrile, butadiene and a carboxylic acid in which the content of acrylonitrile is less than 35.0 wt.-% and the content of carboxylic acid is less than 10.0 wt.-%, with the content of butadiene corresponding to the remainder. Even more preferred nitrile rubbers may comprise the following quantities: 20.0 wt.-% to 30.0 wt.-% of acrylonitrile polymer, 4.0 wt.-% to 6.0 wt.-% of carboxylic acid and most of the remainder is butadiene.
The use of nitrogenous polymers, especially of polyamides, is especially favorable within the scope of the present invention. Especially preferred are polyamide 11, polyamide 12, polyamide 46, polyamide 6, polyamide 6-3-T, polyamide 6-terephthalic acid copolymer, polyamide 66, polyamide 69, polyamide 610, polyamide 612, polyamide 6I, polyamide MXD 6 and/or polyamide PDA-T, especially polyamide 12.
Moreover, also ultrahigh-molecular polyethylenes (UHMWPE) are especially beneficial to the purposes of the present invention, especially those having an average molar mass of more than 1000 kg/mol, preferably more than 2000 kg/mol, especially preferred more than 3000 kg/mol, especially more than 5000 kg/mol. The average molecular weight favorably is no more than 10000 kg/mol. The density of especially suited ultrahigh-molecular polyethylenes is within the range from 0.94-0.99 g/cm3. The crystallinity of especially suited ultrahigh-molecular polyethylenes is within the range from 50% to 90%. The tensile strength of especially suited ultrahigh-molecular polyethylenes is within the range from 30N/mm2 to 50N/mm2. The tensile E modulus of especially suited ultrahigh-molecular polyethylenes is within the range from 800N/mm2 to 2700N/mm2. The melting range of especially suited ultrahigh-molecular polyethylenes is within the range from 135° C. to 155° C.
Furthermore, also the use of absorbable polymers is especially expedient. The term “resorption/absorption” (lat. resorbere=“to suck”) is understood to be the absorption of matter in biological systems, especially into the human organism. Of current interest are especially those materials which can be used to produce absorbable implants.
Absorbable polymers especially preferred according to the invention comprise repeated units of the lactic acid, the hydroxybutyric acid and/or the glycolic acid, of preference of the lactic acid and/or the glycolic acid, especially of the lactic acid. Polylactic acids are especially preferred.
By “polylactic acid” (polylactides) polymers are understood which are structured of lactic acid units. Said polylactic acids are usually prepared by condensation of lactic acids but are also obtained during ring-opening polymerization of lactides under suitable conditions.
Absorbable polymers especially suited according to the invention include poly(glycolide-co-L-lactide), poly(L-lactide), poly(L-lactide-co-ε-caprolactone), poly(L-lactide-co-glycolide), poly(L-lactide-co-D,L-lactide), poly(D,L-lactide-co-glycolide) as well as poly(dioxanone), wherein lactic acid polymers, especially poly-D-, poly-L- or poly-D,L-lactic acids, above all poly-L-lactic acids (PLLA) and poly-D,L-lactic acids, are especially preferred according to the invention, wherein especially the use of poly-L-lactic acids (PLLA) is extraordinarily advantageous.
In accordance with the invention, poly-L-lactic acid (PLLA) preferably has the following structure
wherein n is an integer, preferably larger than 10.
Poly-D,L-lactic acid preferably has the following structure
wherein n is an integer, preferably larger than 10.
Lactic acid polymers suited for the purpose of the present invention are, for example, commercially available by Evonik Nutrition & Care GmbH under the brand names Resomer® GL 903, Resomer® L 206 S, Resomer® L 207 S, Resomer® R 208 G, Resomer® L 209 S, Resomer® L 210, Resomer® L 210 S, Resomer® LC 703 S, Resomer® LG 824 S, Resomer® LG 855 S, Resomer® LG 857 S, Resomer® LR 704 S, Resomer® LR 706 S, Resomer® LR 708, Resomer® LR 927 S, Resomer® RG 509 S and Resomer® X 206 S.
Absorbable polymers especially beneficial to the purposes of the present invention, which preferably are absorbable polyesters, preferably lactic acid polymers, especially preferred poly-D-, poly-L- or poly-D,L-lactic acids, especially poly-L-lactic acids, have a number average molecular weight (Mn), preferably determined by gel permeation chromatography against narrowly distributed polystyrene standards or by final group titration, of more than 500 g/mol, preferably more than 1,000 g/mol, especially preferred more than 5,000 g/mol, appropriately more than 10,000 g/mol, especially more than 25,000 g/mol. On the other hand, the number average of preferred absorbable polymers is less than 1,000,000 g/mol, appropriately less than 500,000 g/mol, favorably less than 100,000 g/mol, especially not exceeding 50,000 g/mol. A number average molecular weight within the range from 500 g/mol to 50,000 g/mol has particularly proven within the scope of the present invention.
The weight average molecular weight (Mw) of preferred absorbable polymers, which preferably are absorbable polyesters, favorably lactic acid polymers, especially preferred poly-D-, poly-L- or poly-D,L-lactic acids, especially poly-L-lactic acids, preferably determined by gel permeation chromatography against narrowly distributed polystyrene standards, of preference ranges from 750 g/mol to 5,000,000 g/mol, preferably from 750 g/mol to 1,000,000 g/mol, especially preferred from 750 g/mol to 500,000 g/mol, especially from 750 g/mol to 250,000 g/mol, and the polydispersity of said polymers favorably ranges from 1.5 to 5.
The inherent viscosity of especially suited absorbable polymers, which preferably are lactic acid polymers, especially preferred poly-D-, poly-L- or poly-D,L-lactic acids, especially poly-L-lactic acids, measured in chloroform at 25° C., 0.1% of polymer concentration, ranges from 0.3 dl/g to 8.0 dl/g, of preference from 0.5 dl/g to 7.0 dl/g, especially preferred from 0.8 dl/g to 2.0 dl/g, especially from 0.8 dl/g to 1.2 dl/g.
Further, the inherent viscosity of especially suited absorbable polymers, which preferably are lactic acid polymers, especially preferred poly-D-, poly-L- or poly-D,L-lactic acids, especially poly-L-lactic acids, measured in hexafluoro-2-propanol at 30° C., 0.1% polymer concentration, ranges from 1.0 dl/g to 2.6 dl/g, especially from 1.3 dl/g to 2.3 dl/g.
Within the scope of the present invention, moreover polymers, favorably thermoplastic polymers, of preference lactic acid polymers, especially preferred poly-D-, poly-L- or poly-D,L-lactic acids, especially poly-L-lactic acids, having a glass transition temperature of more than 20° C., favorably more than 25° C., preferably more than 30° C., especially preferred more than 35° C., especially more than 40° C., are extremely advantageous. Within the scope of an extraordinarily preferred embodiment of the present invention, the glass transition temperature of the polymer is within the range from 35° C. to 70° C., favorably within the range from 55° C. to 65° C., especially within the range from 60° C. to 65° C.
Furthermore, polymers, favorably thermoplastic polymers, of preference lactic acid polymers, especially preferred poly-D-, poly-L- or poly-D,L-lactic acids, especially poly-L-lactic acids, which exhibit a melting temperature of more than 50° C., favorably of at least 60° C., preferably of more than 150° C., especially preferred within the range from 130° C. to 210° C., especially within the range from 175° C. to 195° C., are especially suited.
The glass temperature and the melting temperature of the polymer are preferably established by means of differential scanning calorimetry, abbreviated to DSC. In this context, the following procedure has especially proven itself:
Carrying out DSC measurement under nitrogen on a Mettler-Toledo DSC 30S. Calibration is preferably carried out with indium. The measurements are preferably carried out under dry oxygen-free nitrogen (flow rate: preferably 40 ml/min). The sample weight is preferably selected to be between 15 mg/g and 20 mg/g. The samples are initially heated from 0° C. to preferably a temperature above the melting temperature of the polymer to be tested, then cooled to 0° C. and a second time heated from 0° C. to said temperature at a heating rate of 10° C./min.
Polyamides, UHMWPE as well as absorbable polymers, above all absorbable polyesters such as poly butyric acid, polyglycolic acid (PGA), lactic acid polymers (PLA) and lactic acid copolymers are especially preferred as thermoplastic polymers, with lactic acid polymers and lactic acid copolymers, especially poly-L-lactide, poly-D,L-lactide, copolymers of D,L-PLA and PGA, have particularly proven themselves according to the invention.
For the objectives of the present invention especially the following polymers are particularly suited:
Within the scope of the present invention, the small particles usable for the production of said composite powder comprise at least one calcium salt. Especially suited calcium salts comprise calcium phosphates, especially Ca3(PO4)2, CaHPO4, Ca(H2PO4)2 and/or Ca5(PO4)3(OH), and calcium carbonate, especially precipitated calcium carbonate particles. For the purpose of the present invention, calcium carbonates have turned out to be particularly advantageous.
The form of the calcium salt, preferred of the calcium carbonate, especially of the precipitated calcium carbonate particles, is not subject to any further restrictions and can be adapted to the concrete application. Of preference, scalenohedral, rhombohedral, needle-shaped, plate-shaped or ball-shaped (spherical) particles are used, however.
Within the scope of a very particularly preferred embodiment of the present invention, spherical precipitated calcium carbonate particles are used, as they typically show an isotropic property profile. Accordingly, expediently the particles of the resulting composite powder equally excel by a preferably isotropic property profile.
In accordance with the invention, the term “calcium carbonate particles” also comprises fragments of particles which are obtainable e.g. by grinding the calcium carbonate. The fraction of fragments, especially of ball fragments, is preferably less than 95%, preferred less than 75%, especially preferred less than 50%, especially less than 25%, each related to the total quantity of preferably precipitated calcium carbonate.
The aspect ratio (side ratio) of the calcium salt, preferred of the calcium carbonate, especially of the precipitated calcium carbonate particles, is preferably less than 5, of preference less than 4, especially preferred less than 3, favorably less than 2, even more preferred less than 1.5, particularly preferred in the range from 1.0 to 1.25, preferably less than 1.1, especially less than 1.05.
The aspect ratio (side ratio) of the calcium salt, preferred of the calcium carbonate, especially of the precipitated calcium carbonate particles, in this context denotes the quotient of maximum and minimum particle diameters. It is preferably established by means of electron-microscopic images as means value (number average). In this context, for spherical calcium carbonate particles preferably only particles having a particle size in the range from 0.1 μm to 40.0 μm, especially in the range from 0.1 μm to 30.0 μm are considered. For rhombohedral calcium salt particles, especially for rhombohedral calcium carbonate particles, preferably only particles having a particle size in the range from 0.1 μm to 30.0 μm, especially in the range from 0.1 μm to 20.0 μm are considered. For other calcium salt particles, especially for calcium carbonate particles, preferably only particles having a particle size in the range from 0.1 μm to 2.0 μm are considered.
Moreover, preferably at least 90%, favorably at least 95% of all particles have an aspect ratio (side ratio) of less than 5, preferably less than 4, especially preferred less than 3, favorably less than 2, even more preferred less than 1.5, very particularly preferred ranging from 1.0 to 1.25, preferably less than 1.1, especially less than 1.05.
Further, spherical calcium carbonate particles are extraordinarily appropriate.
In accordance with the invention, the calcium salt particles, especially the preferably spherical calcium carbonate particles, are expediently provided predominantly in single parts. Further, minor deviations from the perfect particle shape, especially from the perfect ball shape, are accepted as long as the properties of the particles are not basically modified. In this way, the surface of the particles may include occasional defects or additional depositions.
Within the scope of an especially preferred variant of the present invention, the calcium salt particles, preferred the calcium carbonate particles, especially the precipitated calcium carbonate particles, are preferably spherical and substantially amorphous. The term “amorphous” in this context refers to such calcium salt modifications in which the atoms at least partly do not form ordered structures but form an irregular pattern and therefore only have a short-range order but not a long-range order. Herefrom crystalline modifications of the calcium salt, such as e.g. calcite, vaterite and aragonite, in which the atoms have both a short-range order and a long-range order have to be distinguished.
Within the scope of this preferred variant of the present invention, the presence of crystalline parts is not categorically ruled out. Preferably the fraction of crystalline calcium salts, especially of crystalline calcium carbonate, is less than 50 wt.-%, especially preferred less than 30 wt.-%, quite particularly preferred less than 15 wt.-%, especially less than 10 wt.-%, however. Within the scope of an especially preferred variant of the present invention, the fraction of crystalline calcium salts, especially of crystalline calcium carbonate, is less than 8.0 wt.-%, preferably less than 6.0 wt.-%, appropriately less than 4.0 wt.-%, especially preferred less than 2.0 wt.-%, quite particularly preferred less than 1.0 wt.-%, especially less than 0.5 wt.-%, each related to the total weight of the calcium salt.
For establishing the amorphous and the crystalline fractions, X-ray diffraction with an internal standard, preferably quartz, in combination with Rietveld refinement has particularly proven itself.
Within the scope of this preferred embodiment of the present invention, the calcium salt particles, preferred the preferably amorphous calcium carbonate particles, are favorably stabilized by at least one substance, especially at least one surface-active substance, which is preferably arranged on the surface of the calcium salt particles, especially on the surface of the preferably spherical calcium carbonate particles. “Surface-active substances” in accordance with the present invention expediently denote organic compounds which strongly enrich themselves from their solution at boundary surfaces (water/calcium salt particles, preferred calcium carbonate particles) and thus reduce the surface tension, preferably measured at 25° C. For further details, reference is made to technical literature, especially to Römpp-Lexikon Chemie/publisher Jürgen Falbe; Manfred Regitz. Revised by Eckard Amelingmeier; Stuttgart, New York; Thieme; Volume 2: Cm-G; 10th Edition (1997); keyword: “surface-active substances”.
Of preference, the substance, especially the surface-active substance, has a molar mass of more than 100 g/mol, preferably more than 125 g/mol, especially more than 150 g/mol, and satisfies the formula R—Xn.
The remainder R stands for a remainder comprising at least 1, preferably at least 2, of preference at least 4, especially preferred at least 6, especially at least 8, carbon atoms, preferably for an aliphatic or cycloaliphatic remainder which may comprise further remainders X, where necessary, and which may have one or more ether links, where necessary.
The remainder X stands for a group which comprises at least on oxygen atom as well as at least one carbon atom, sulfur atom, phosphorus atom and/or nitrogen atom, preferred at least one phosphorus atom and/or at least one carbon atom. Especially preferred are the following groups:
The remainders R1, R2 and R3 in this context stand independently of each other for hydrogen or an alkyl group having 1 to 5 carbon atoms. One of the remainders R1, R2 and R3 may also be a remainder R.
Preferred counter-ions for the afore-mentioned anions are metal cations, especially alkaline metal cations, preferred Na+ and K+, as well as ammonium ions.
Preferred counter-ions for the afore-mentioned cations are hydroxy ions, hydrogen carbonate ions, carbonate ions, hydrogen sulfate ions, sulfate ions and halide ions, especially chloride and bromide ions.
n stands for a preferably integer within the range from 1 to 20, preferred within the range from 1 to 10, especially within the range from 1 to 5.
Substances especially suited for the purposes of the present invention comprise alkyl carboxylic acids, alkyl carboxylates, alkyl sulfonic acids, alkyl sulfonates, alkyl sulfates, alkyl ether sulfates having preferably 1 to 4 ethylene glycol ether units, fatty alcohol ethoxylate having preferably 2 to 20 ethylene glycol ether units, alkyl phenol ethoxylate, possibly substituted alkyl phosphonic acids, possibly substituted alkyl phosphonates, sorbitan fatty acid esters, alkyl poly glucosides, N-methyl glucamides, homopolymers and copolymers of the acrylic acid and the corresponding salt forms and block copolymers thereof.
A first group of especially advantageous substances are possibly substituted alkyl phosphonic acids, especially amino-tri-(methylene phosphonic acid), 1-hydroxy ethylene-(1,1-diphosphonic acid), ethylene diamine-tetra-(methylene phosphonic acid), hexamethylene diamine-tetra-(methylene phosphonic acid), diethylene triamine-penta-(methylene phosphonic acid), as well as possibly substituted alkyl phosphonates, especially of the afore-mentioned acids. Said compounds are known as multifunctional sequestration means for metal ions and stone inhibitors.
Furthermore, also homopolymers and copolymers, preferably homopolymers, of the acrylic acid as well as the corresponding salt forms thereof have especially proven themselves, in particular those having a weight average molecular weight within the range from 1,000 g/to 10,000 g/mol.
Further, the use of block copolymers, preferably of double-hydrophilic block copolymers, especially of polyethylene oxide or polypropylene oxide, is especially appropriate.
The fraction of the preferably surface-active substances may basically be freely selected and specifically adjusted for the respective application. However, it is preferred to be within the range from 0.1 wt.-% to 5.0 wt.-%, especially within the range from 0.3 wt.-% to 1.0 wt.-%, based on the calcium salt content, especially the CaCO3 content, of the particles.
The preferably spherical, preferably amorphous calcium salt particles, especially the calcium carbonate particles, may be prepared in a way known per se, e.g. by hydrolysis of dialkyl carbonate or of alkylene carbonate in a solution comprising calcium cations.
The preparation of non-stabilized spherical calcium carbonate particles is described in detail e.g. in the patent application WO 2008/122358 the disclosure of which, especially relating to especially expedient variants of the preparation of said non-stabilized spherical calcium carbonate particles, is explicitly incorporated here by reference.
The hydrolysis of the dialkyl carbonate or the alkylene carbonate is usefully carried out in the presence of a hydroxide.
Substances preferred for the purpose of the present invention which contain Ca2+ ions are calcium halides, preferably CaCl2, CaBr2, especially CaCl2, as well as calcium hydroxide. Within the scope of the first especially preferred embodiment of the present invention CaCl2 is used. In a further especially preferred embodiment of the present invention Ca(OH)2 is used.
Within the scope of a first especially preferred embodiment of the present invention, a dialkyl carbonate is used. Particularly suited dialkyl carbonates comprise 3 to 20, preferably 3 to 9, carbon atoms, especially dimethyl carbonate, diethyl carbonate, di-n-propyl carbonate, di-iso-propyl carbonate, di-n-butyl carbonate, di-sec-butyl carbonate and di-tert-butyl carbonate, with dimethyl carbonate being extraordinarily preferred in this context.
In another especially preferred embodiment of the present invention, an alkylene carbonate is reacted. Especially expedient alkylene carbonates comprise 3 to 20, preferred 3 to 9, especially preferred 3 to 6, carbon atoms and include especially those compounds containing a ring of 3 to 8, preferred 4 to 6, especially 5, atoms having preferably 2 oxygen atoms and otherwise carbon atoms. Propylene carbonate (4-methyl-1,3-dioxolane) has especially proven itself in this context.
Alkaline metal hydroxides, especially NaOH and calcium hydroxide, have turned out to be especially suited hydroxides. Within the scope of a first especially preferred embodiment of the present invention, NaOH is used. Within the scope of another especially preferred embodiment of the present invention Ca(OH)2 is used.
Further, the molar ratio of Ca2+, preferably of calcium chloride, to OH−, preferably alkali metal hydroxide, in the reaction mixture is preferably higher than 0.5:1 and especially preferred within the range of >0.5:1 to 1:1, especially within the range from 0.6:1 to 0.9:1.
The molar ratio of Ca2+, preferably of calcium chloride, to dialkyl carbonate and/or alkylene carbonate in the reaction mixture favorably is within the range from 0.9:1.5 to 1.1:1, especially preferred within the range from 0.95:1 to 1:0.95. Within the scope of a particularly expedient variant of the present invention, dialkyl carbonate and/or alkylene carbonate and Ca2+, especially calcium chloride, are used to be equimolar.
Within a first particularly preferred variant of the present invention, it is not Ca(OH)2 which is used as OH− source. The components for the reaction are favorably used in the following concentrations:
The respective indicated concentrations relate to the concentrations of the given components in the reaction mixture.
Within a further especially preferred variant of the present invention, Ca(OH)2, preferred limewater, especially saturated limewater, is used as OH− source. The components for the reaction are favorably used in the following concentrations:
The respective indicated concentrations relate to the concentrations of said components in the reaction mixture.
The reaction of the components is preferably carried out at a temperature within the range from 15° C. to 30° C.
The concrete size of the calcium salt particles, especially the calcium carbonate particles, can be controlled via oversaturation in a manner known per se.
The calcium salt particles, especially the calcium carbonate particles, precipitate from the reaction mixture under the afore-mentioned conditions.
The preferably amorphous calcium salt particles, especially the preferably amorphous calcium carbonate particles, are expediently stabilized by addition of the preferably surface-active substance to the reaction mixture.
Said addition of the substance should not take place before the start of reaction to form the calcium salt particles, especially the calcium carbonate particles, i.e. not before addition of the educts, preferably no earlier than 1 minute, preferably no earlier than 2 minutes, appropriately no earlier than 3 minutes, especially preferred no earlier than 4 minutes, especially no earlier than 5 minutes, after mixing the educts. Further, the point in time of the addition should be selected so that the preferably surface-active substance is added shortly before the end of precipitation and as shortly as possible before the start of conversion of the preferably amorphous calcium salt, especially the amorphous calcium carbonate, to a crystalline modification, as in this way the yield and the purity of the “stabilized spherical amorphous calcium salt particles” can be maximized. If the preferably surface-active substance is added earlier, usually a bimodal product is obtained which comprises, apart from the desired stabilized spherical amorphous calcium salt particles, ultra-fine amorphous calcium salt particles as a side-product. If the preferably surface-active substance is added later, then the conversion of the desired “stabilized calcium salt particles” to crystalline modifications already starts.
For this reason, the preferably surface-active substance is preferably added at a pH value less than or equal to 11.5, preferably less than or equal to 11.3, especially less than or equal to 11.0. Especially favorable is an addition at a pH value in the range from 11.5 to 10.0, of preference in the range from 11.3 to 10.5, especially in the range from 11.0 to 10.8, each measured at the reaction temperature, preferably at 25° C.
The resulting stabilized preferably spherical amorphous calcium salt particles can be dehydrated and dried in a way known per se, e.g. by centrifugation. Washing with acetone and/or drying in the vacuum drying cabinet is no longer absolutely necessary.
By drying “calcium salt particles having low structural water content”, especially “calcium carbonate particles having low structural water content” are obtainable from the “stabilized calcium salt particles”.
For the purposes of the present invention, the calcium salt particles obtained are preferably dried such that they have the desired residual water content. For this, a procedure in which the calcium salt particles are pre-dried preferably at first at a temperature up to 150° C. and subsequently the calcium salt particles are dried preferably at a temperature ranging from more than 150° C. to 250° C., preferred ranging from 170° C. to 230° C., especially preferred ranging from 180° C. to 220° C., especially ranging from 190° C. to 210° C. Drying is preferably carried out in the circulating air drying cabinet. Accordingly, the calcium salt particles are expediently dried for at least 3 h, especially preferred for at least 6 h, especially for at least 20 h.
Within the scope of another especially preferred variant of the present invention, the calcium salt particles, especially the preferably precipitated calcium carbonate particles, are substantially crystalline, especially substantially calcitic. Within the scope of this preferred variant of the present invention, the presence of other, especially of amorphous parts is not categorically excluded. Preferably the fraction of other non-crystalline calcium salt modifications, especially of non-crystalline calcium carbonate modifications, is less than 50 wt.-%, especially preferred less than 30 wt.-%, particularly preferred less than 15 wt.-%, especially less than 10 wt.-%, however. Moreover, the fraction of non-calcitic calcium carbonate modifications preferably is less than 50 wt.-%, especially preferred less than 30 wt.-%, particularly preferred less than 15 wt.-%, especially less than 10 wt.-%.
For establishing the amorphous and crystalline fractions, the X-ray diffraction with an internal standard, preferably aluminum oxide, in combination with Rietveld refinement has particularly proven itself.
The mean diameter of the small particles is within the range from 0.01 μm to 1.0 mm, preferred within the range from 0.05 μm to 50.0 μm, especially within the range from 2.5 μm to 30.0 μm.
Within the scope of an especially preferred embodiment of the present invention, the mean diameter of the small particles is more than 3.0 μm, preferably more than 4.0 μm, expediently more than 5.0 μm, expediently more than 6.0 μm, preferred more than 7.0 μm, especially preferred more than 8.0 μm, yet more preferred more than 9.0 μm, particularly preferred more than 10.0 μm, yet more preferred more than 11.0 μm, above all more than 12.0 μm, especially more than 13.0 μm.
For small particles comprising scalenohedral calcium salt particles, especially scalenohedral calcium carbonate particles, the mean diameter of the small particles favorably is within the range from 0.05 μm to 5.0 μm, preferred within the range from 0.05 μm to 2.0 μm, preferably less than 1.75 μm, especially preferred less than 1.5 μm, especially less than 1.2 μm. Furthermore, the mean particle diameter in this case is favorably more than 0.1 μm, preferably more than 0.2 μm, especially more than 0.3 μm.
Furthermore, also small particles comprising scalenohedral calcium salt particles, especially scalenohedral calcium carbonate particles, having a mean diameter of the small particles favorably within the range from 1.0 μm to 5.0 μm, preferably less than 4.5 μm, especially preferred less than 4.0 μm, especially less than 3.5 μm, have particularly proven themselves. Furthermore, the mean particle diameter in this case is favorably more than 1.5 μm, preferably more than 2.0 μm, especially more than 3.0 μm.
For small particles comprising rhombohedral calcium salt particles, especially rhombohedral calcium carbonate particles, the mean diameter of the small particles favorably is within the range from 0.05 μm to 30.0 μm, preferred within the range from 0.05 μm to 2.0 μm, preferably less than 1.75 μm, especially preferred less than 1.5 μm, especially less than 1.2 μm. Furthermore, the mean particle diameter in this case is favorably more than 0.1 μm, preferably more than 0.2 μm, especially more than 0.3 μm.
Furthermore, also small particles comprising rhombohedral calcium salt particles, especially rhombohedral calcium carbonate particles, having a mean diameter favorably within the range from 1.0 μm to 30.0 μm, preferred within the range from 1.0 μm to 20.0 μm, preferably less than 18.0 μm, especially preferred less than 16.0 μm, especially less than 14.0 μm, have particularly proven themselves. Furthermore, in this case the mean particle diameter is favorably more than 2.5 μm, preferably more than 4.0 μm, especially more than 6.0 μm.
For small particles comprising needle-shaped calcium salt particles, especially needle-shaped calcium carbonate particles, the mean diameter of the small particles is favorably within the range from 0.05 μm to 2.0 μm, preferably less than 1.5 μm, especially preferred less than 1.0 μm, especially less than 0.75 μm. Furthermore, the mean particle diameter in this case is favorably more than 0.1 μm, preferably more than 0.2 μm, especially more than 0.3 μm.
For small particles comprising needle-shaped calcium salt particles, especially needle-shaped calcium carbonate particles, the aspect ratio of the particles is preferably more than 2, preferred more than 5, especially preferred more than 10, especially more than 20. Furthermore, the length of the needles preferably is within the range from 0.1 μm to 100.0 μm, preferred within the range from 0.3 μm to 85.0 μm, especially within the range from 0.5 μm to 70.0 μm.
For small particles comprising plate-shaped calcium salt particles, especially plate-shaped calcium carbonate particles, the mean diameter of the small particles is favorably within the range from 0.05 μm to 2.0 μm, preferably less than 1.75 μm, especially preferred less than 1.5 μm, especially less than 1.2 μm. Furthermore, the mean particle diameter in this case is favorably more than 0.1 μm, preferably more than 0.2 μm, especially more than 0.3 μm.
For small particles comprising spherulitic (spherical) calcium carbonate particles the mean diameter of the small particles expediently is more than 2.5 μm, favorably more than 3.0 μm, preferred more than 4.0 μm, especially preferred more than 5.0 μm, especially more than 6.0 μm. Furthermore, the mean particle diameter is expediently less than 30.0 μm, favorably less than 20.0 μm, preferred less than 18.0 μm, especially preferred less than 16.0 μm, especially less than 14.0 μm.
The afore-mentioned mean particles sizes of the small particles are established, within the scope of the present invention, expediently by evaluation of scanning electron microscope images (SEM images), wherein preferably only particles having a minimum size of 0.01 μm are considered and a number average is formed over preferably at least 20, especially preferred at least 40 particles. Furthermore, also sedimentation analysis methods have especially proven themselves, primarily for small particles comprising needle-shaped calcium salt particles, especially needle-shaped calcium carbonate particles, wherein in this context the use of a Sedigraph 5100 (Micromeritics GmbH) is of particular advantage.
In the case of small particles comprising non-spherical calcium salt particles, especially non-spherical calcium carbonate particles, preferably the ball-equivalent particle size is focused.
The size distribution of the small particles comprising calcium salt particles, especially calcium carbonate particles, is comparatively narrow and preferably such that at least 90.0 wt.-% of all small particles have a particle diameter within the range from mean particle diameter −50%, preferably within the range from mean particle diameter −40%, especially within the range from mean particle diameter −30%, to mean particle diameter +70%, preferably mean particle diameter +60%, especially mean particle diameter +50%. Accordingly, the size distribution is preferably established by means of scanning tunneling microscopy.
The form factor of the small particles, currently defined as the quotient of minimum particle diameter and maximum particle diameter, expediently is more than 0.90, especially preferred more than 0.95 expediently for at least 90%, favorably for at least 95% of all particles. In this context, for small particles comprising spherical calcium carbonate particles preferably only particles having a particle size within the range from 0.1 μm to 30.0 μm are considered. For small particles comprising rhombohedral calcium salt particles, especially rhombohedral calcium carbonate particles, preferably only particles having a particle size within the range from 0.1 μm to 20.0 μm are considered. For small particles comprising other calcium salt particles, especially other calcium carbonate particles, preferably only particles having a particle size within the range from 0.1 μm to 2.0 μm are considered.
The calcium salt particles, especially the calcium carbonate particles, favorably further excel by a comparatively low water content. They expediently have a water content (residual moisture at 200° C.), based on their total weight, not exceeding 5.0 wt.-%, preferably not exceeding 2.5 wt.-%, preferably not exceeding 1.0 wt.-%, especially preferred not exceeding 0.5 wt.-%, yet more preferred less than 0.4 wt.-%, expediently less than 0.3 wt.-%, favorably less than 0.2 wt.-%, especially within the range from >0.1 wt.-% to <0.2 wt.-%.
Within the present invention, the water content of the calcium salt particles, especially of the calcium carbonate particles, is established preferably by means of thermal gravimetry or by means of a rapid infrared drier, e.g. MA35 or MA45 by Sartorius or halogen moisture analyzer HB43 by Mettler, wherein the measurement is preferably carried out under nitrogen (nitrogen flow rate of preferably 20 ml/min) and expediently via the temperature range of 40° C. or less to 250° C. or more. Further, the measurement is preferably carried out at a heating rate of 10° C./min.
The specific surface of the calcium salt particles, especially the calcium carbonate particles, is preferably within the range from 0.1 m2/g to 100 m2/g, especially preferred within the range from 0.1 m2/g to 20.0 m2/g, especially within the range from 4.0 m2/g to 12.0 m2/g. For rhombohedral calcium salt particles, especially for rhombohedral calcium carbonate particles, the specific surface within the scope of an especially preferred variant of the present invention is less than 1.0 m2/g, preferred less than 0.75 m2/g, especially less than 0.5 m2/g, wherein the mean diameter of the rhombohedral calcium salt particles, especially the rhombohedral calcium carbonate particles, is favorably more than 2.5 μm, preferably more than 4.0 μm, especially more than 6.0 μm.
For spherical calcium carbonate particles, the specific surface within the scope of an especially preferred variant of the present invention is less than 3.0 m2/g, preferred less than 2.0 m2/g, especially less than 1.5 m2/g. Furthermore, the specific surface in this case favorably is more than 0.25 m2/g, preferably more than 0.5 m2/g, especially more than 0.75 m2/g.
Particularly preferred in this context are calcium salt particles, especially calcium carbonate particles, the specific surface of which remains relatively constant during drying and preferably varies by no more than 200%, preferred by no more than 150%, especially by no more than 100%, each related to the initial value.
The basicity of the calcium salt particles, especially the calcium carbonate particles, is comparatively low. Its pH value, measured according to EN ISO 787-9, is preferably less than 11.5, preferred less than 11.0, especially less than 10.5.
The preferably spherical calcium carbonate particles may be prepared by carbonizing an aqueous calcium hydroxide (Ca(OH)2) suspension. For this, expediently CO2 or a CO2-containing gas mixture is fed into a calcium hydroxide suspension.
A procedure in which
The concentration of the calcium hydroxide suspension is not subject to any particular restrictions. However, a concentration within the range from 1 g CaO/l to 100 g CaO/l, preferred within the range from 10 g CaO/l to 90 g CaO/l, especially within the range from 50 g CaO/l to 80 g CaO/l is especially favorable.
As amino tri alkylene phosphonic acid, preferably amino tri methylene phosphonic acid, amino tri ethylene phosphonic acid, amino tri propylene phosphonic acid and/or amino tri butylene phosphonic acid, especially amino tri methylene phosphonic acid is/are added.
The conversion of the reaction can be controlled by the quantity of CO2 introduced. However, the introduction of carbon dioxide or the carbon dioxide-containing gas mixture is preferably carried out until the reaction mixture has a pH value of less than 9, preferably less than 8, especially less than 7.5.
Furthermore, the carbon dioxide or the carbon dioxide-containing gas mixture is expediently introduced at a gas flow rate within the range from 0.02 l CO2/(h*g Ca(OH)2) to 2.0 l CO2/(h*g Ca(OH)2), preferably within the range from 0.04 l CO2/(h*g Ca(OH)2) to 1.0 l CO2/(h*g Ca(OH)2), especially preferred within the range from 0.08 l CO2/(h*g Ca(OH)2) to 0.4 l CO2/(h*g Ca(OH)2), especially within the range from 0.12 l CO2/(h*g Ca(OH)2) to 0.2 l CO2/(h*g Ca(OH)2) into the calcium hydroxide suspension.
Incidentally, the conversion of the calcium hydroxide suspension with the carbon dioxide or the carbon dioxide-containing gas mixture is carried out preferably at a temperature of less than 25° C., preferably less than 20° C., especially less than 15° C. On the other hand, the reaction temperature preferably is more than 0° C., preferably more than 5° C., especially more than 7° C.
The at least one amino tri alkylene phosphonic acid is expediently added in the course of the reaction, preferably after an abrupt drop of the conductance of the reaction mixture. Expediently, the at least one amino tri alkylene phosphonic acid is added as soon as the conductivity of the reaction mixture decreases by more than 0.5 mS/cm/min. The decrease of the conductivity of the reaction mixture preferably amounts to at least 0.25 mS/cm within 30 seconds, especially at least 0.5 mS/cm within 60 seconds. Within the scope of an especially preferred embodiment of the present invention, the at least one amino tri alkylene phosphonic acid is added at the end of precipitation of the basic calcium carbonate (BCC; 2CaCO3*Ca(OH)2*nH2O).
The calcium carbonate particles precipitate from the reaction mixture under the afore-mentioned conditions and can be separated and dried in a way known per se.
Within the scope of a preferred embodiment of the present invention, the composite powder according to the invention used in the implant contains a mixture comprising calcium carbonate and further calcium salts, especially calcium phosphates, especially Ca3(PO4)2, CaHPO4, Ca(H2PO4)2 and/or Ca5(PO4)3(OH). The weight ratio of calcium carbonate to calcium phosphate preferably is in the range from 99:1 to 1:99, especially in the range from 50:50 to 99:1.
Within the scope of a preferred embodiment, the small particles comprise inhibiting calcium carbonate particles. In this context, “inhibiting calcium carbonate particles” denote calcium carbonate particles which as an additive in polymers decelerate, at the best completely suppress, the acid-catalyzed degradation of the polymer as compared to the same polymer without an additive.
Expediently, the small particles are obtainable by a process in which calcium carbonate particles are coated with a composition which contains, each related to its total weight, a mixture of at least 0.1 wt.-% of at least one calcium complexing agent and/or at least one conjugated base which is an alkali metal salt or calcium salt of a weak acid, together with at least 0.1 wt.-% of at least one weak acid.
The anions of the calcium complexing agent and of the conjugated base may be equal, within the scope of this embodiment, although this is no absolute requirement.
Sodium phosphates, i.e. sodium salts of phosphoric acids, especially sodium salts of orthophosphoric acid, metaphosphoric acid and polyphosphoric acid, have turned out to be especially advantageous as calcium complexing agents. Preferred sodium phosphates comprise sodium orthophosphates such as primary sodium dihydrogen phosphate NaH2PO4, secondary sodium dihydrogen phosphate Na2HPO4 and tertiary trisodium phosphate Na3PO4; sodium iso polyphosphates such as tetrasodium diphosphate (sodium pyrophosphate) Na4P2O7, pentasodium triphosphate (sodium tripolyphosphate) Na5P3O10; as well as higher-molecular sodium phosphates such as sodium metaphosphates and sodium polyphosphates such as fused or thermal phosphates, Graham's salt (approximate composition Na2O*P2O5, occasionally also referred to as sodium hexametaphosphate), Kurrol's salt and Maddrell salt. Especially preferred, sodium hexametaphosphate is used according to the invention. The use of the afore-mentioned phosphates is especially advantageous in a composite powder for implants, as in this case the phosphates additionally promote the osseous structure.
Further suited calcium complexing agents include joint multidentate chelate-forming ligands, especially ethylene diamino tetra acetic acid (EDTA), triethylenetetramine, diethylenetriamine, o-phenanthroline, oxalic acid and mixtures thereof.
Weak acids especially suited for the purposes of the present invention have a pKa value, measured at 25° C., of more than 1.0, preferably more than 1.5, especially more than 2.0. At the same time, the pKa value of suited weak acids, measured at 25° C., is preferably less than 20.0, preferred less than 10.0, especially preferred less than 5.0, expediently less than 4.0, especially less than 3.0. Weak acids extraordinarily suited according to the invention comprise phosphoric acid, metaphosphoric acid, hexametaphosphoric acid, citric acid, boric acid, sulfurous acid, acetic acid and mixtures thereof. Phosphoric acid is used especially preferred as weak acid.
Conjugated bases preferred according to the invention include especially sodium salts or calcium salts of the afore-mentioned weak acids, with sodium hexametaphosphate being particularly preferred.
The inhibiting calcium carbonate particles can be prepared in a way known per se by coating calcium carbonate particles with a composition which comprises at least one calcium complexing agent and/or at least one conjugated base which is an alkali metal salt or calcium salt of a weak acid, together with at least one weak acid.
Expediently an aqueous suspension of the calcium carbonate particles to be coated is provided which, based on its total weight, favorably has a content of calcium carbonate particles within the range from 1.0 wt.-% to 80.0 wt.-%, preferred within the range from 5.0 wt.-% to 50.0 wt.-%, especially within the range from 10.0 wt.-% to 25.0 wt.-%.
The coating of the calcium carbonate particles is favorably carried out by adding said substances in pure form or in aqueous solution, wherein aqueous solutions of said components have turned out to be particularly advantageous according to the invention in order to obtain an as homogenous coating as possible of the calcium carbonate particles.
Further, it is especially favorable within the scope of the present invention to add the calcium complexing agent and/or the conjugated base, which is an alkali metal salt or calcium salt of a weak acid, before the weak acid.
The calcium complexing agent or the conjugated base is preferably used in a quantity ranging from 0.1 parts by weight to 25.0 parts by weight, preferred ranging from 0.5 parts by weight to 10.0 parts by weight, especially ranging from 1.0 parts by weight to 5.0 parts by weight, each related to 100 parts by weight of the calcium carbonate particles to be coated. The quantity of the calcium complexing agent or of the conjugated base is expediently selected so that complete coating of the surface of the calcium carbonate particles with the calcium complexing agent of the conjugated base is obtained.
The weak acid is preferably used in a quantity ranging from 0.1 parts by weight to 30.0 parts by weight, preferred ranging from 0.5 parts by weight to 15.0 parts by weight, especially preferred ranging from 1.0 parts by weight to 10.0 parts by weight, especially ranging from 4.0 parts by weight to 8.0 parts by weight, each related to 100 parts by weight of the calcium carbonate particles to be coated.
The inhibiting calcium carbonate particles obtainable in this way are stable in a moderately acid environment, wherein this capacity is due to a buffering action by the absorbed or converted calcium complexing agent or the conjugated base on the surface of the calcium carbonate particles and the weak acid in solution, wherein applying the calcium complexing agent and/or the conjugated base to the surface of the calcium carbonate particles in turn reduces the solubility of the surface of the calcium carbonate particles and thus stabilizes the calcium carbonate particles without the teaching of the present invention being intended to be bound to this theory.
The said composite powder is preferably obtainable by a method in which large particles are combined with small particles, wherein
The small particles preferably are arranged on the surface of the large particles and/or are non-homogeneously spread within the large particles.
Especially for absorbable polymers and for UHMWPE excellent results are achieved, however, when the small particles are arranged on the surface of the large particles and preferably do not completely cover the latter.
“Non-homogeneous” distribution of the small particles or fragments thereof within the large particles in this case means a non-homogeneous (uniform) distribution of the small particles or fragments thereof within the large particles. Preferably, within the particles of the composite powder there is at least a first area comprising at least two, preferably at least three, preferred at least four, especially at least five small particles or fragments thereof and at least another area within the particles of the composite powder which, although taking the same volume and the same shape as the first area, comprises a different number of small particles.
Within the scope of a preferred embodiment of the present invention, the weight ratio of polymer, especially polyamide, to calcium salt, preferred to calcium carbonate, especially to precipitated calcium carbonate, within the particle interior is higher than the weight ratio of polymer, especially polyamide, to calcium salt, preferred to calcium carbonate, especially precipitated calcium carbonate, in the outer area of the particles. Expediently, the weight ratio of polymer, especially polyamide, to calcium salt, preferred to calcium carbonate, especially precipitated calcium carbonate, in the particle interior is higher than 50:50, preferred higher than 60:40, favorably higher than 70:30, especially preferred higher than 80:20, even more preferred higher than 90:10, particularly preferred higher than 95:5, especially higher than 99:1.
Furthermore, the weight ratio of calcium salt, preferred calcium carbonate, especially precipitated calcium carbonate, to polymer, especially polyamide, in the outer area of the particles, preferably in the preferred outer area of the particles, is higher than 50:50, preferred higher than 60:40, favorably higher than 70:30, especially preferred higher than 80:20, even more preferred higher than 90:10, particularly preferred higher than 95:5, especially higher than 99:1.
Within the scope of another preferred embodiment of the present invention, the small particles are arranged on the surface of the large particles and preferably do not completely cover the large particles. Expediently, at least 0.1%, preferred at least 5.0%, especially 50.0%, of the surface of the large particles are not coated with the calcium salt particles, especially not coated with the preferably spherical calcium carbonate particles. This effect is preferably intensified by the gaps between individual calcium salt particles, especially between individual calcium carbonate particles which are preferably formed and result in the formation of appropriate micro-channels for fluid substances, especially for a melt of the polymer of the large particles. Said structure is especially beneficial to applications of the composite powder in laser sintering methods, as in this way uniform and rapid melting of the polymer contained in the composite powder, preferred of the thermoplastic polymer, especially preferred of the absorbable polymer, especially of the lactic acid polymer, is ensured.
The said composite powder is characterized by a specific particle size distribution. On the one hand, the particles of the composite powder preferably have a mean particle size d50 ranging from 10 μm to less than 200 μm, preferred from 20 μm to less than 200 μm, especially preferred from 20 μm to less than 150 μm, favorably from 20 μm to less than 100 μm, especially from 35 μm to less than 70 μm.
Furthermore, the fine fraction of the composite powder preferably is less than 50.0 vol %, preferred less than 45.0 vol %, especially preferred less than 40.0 vol %, even more preferred less than 20.0 vol %, favorably less than 15.0 vol %, expediently less than 10.0 vol %, especially less than 5.0 vol %. The fine fraction denotes, according to the invention, the fraction of the smallest particle population in a bimodal or multimodal grain size distribution related to the total amount in the cumulative distribution curve. In unimodal (monodisperse) grain size distribution, the fine fraction is defined as 0.0 vol %, according to the invention. In this context, all particles present in the product including non-bonded starting material, especially small particles in accordance with the invention as well as fragments of the large and/or small particles in accordance with the invention are considered.
For composite powders having an average particle size d50 ranging from more than 40 μm to less than 200 μm, the fine fraction preferably is such that the fraction of particles within the product having a particle size of less than 20 μm is preferably less than 50.0 vol %, preferred less than 45.0 vol %, especially preferred less than 40.0 vol %, even more preferred less than 20.0 vol %, favorably less than 15.0 vol %, expediently less than 10.0 vol %, especially less than 5.0 vol %, wherein “particles” in this context comprise especially particles of the composite powder in accordance with the invention, small particles in accordance with the invention as well as fragments of the large and/or small particles in accordance with the invention, if they show the said particle size.
For composite powders having a mean particle size d50 ranging from 10 μm to 40 μm, the fine fraction preferably is such that the fraction of particles within the product having a particle size of less than 5 μm is preferably less than 50.0 vol %, preferred less than 45.0 vol %, especially preferred less than 40.0 vol %, even more preferred less than 20.0 vol %, favorably less than 15.0 vol %, expediently less than 10.0 vol %, especially less than 5.0 vol %, wherein “particles” in this context comprise especially particles of the composite powder in accordance with the invention, small particles in accordance with the invention as well as fragments of the large and/or small particles in accordance with the invention, if they show the said particle size.
Furthermore, the density of the fine fraction preferably is less than 2.6 g/cm3, preferred less than 2.5 g/cm3, especially preferred less than 2.4 g/cm3, especially ranging from more than 1.2 g/cm3 to less than 2.4 g/cm3, said value being preferably determined by separating the fine fraction by means of sieving and densitometry at the separated fraction.
Of preference, the particles of the composite powder have a particle size d90 of less than 350 μm, preferably less than 300 μm, preferred less than 250 μm, especially preferred less than 200 μm, especially less than 150 μm. Further, the particle size d90 preferably is more than 50 μm, preferred more than 75 μm, especially more than 100 μm.
Appropriately, the d20/d50 ratio is less than 100%, preferably less than 75%, preferred less than 65%, especially preferred less than 60%, especially less than 55%. Further, the d20/d50 ratio appropriately is more than 10%, preferably more than 20%, preferred more than 30%, especially preferred more than 40%, especially more than 50%.
The afore-mentioned variables d20, d50 and d90 are defined as follows within the scope of the present invention:
d20 denotes the particle size of the particle size distribution at which 20% of the particles have a particle size of less than the given value and 80% of the particles have a particle size of more than or equal to the given value.
d50 denotes the mean particle size of the particle size distribution. 50% of the particles have a particle size of less than the given value and 50% of the particles have a particle size of more than or equal to the given value.
d90 denotes the particle size of the particle size distribution at which 90% of the particles have a particle size of less than the given value and 10% of the particles have a particle size of more than or equal to the given value.
The particle size distribution according to the invention can be obtained in a way known per se by sizing the composite powder, i.e. by separating a disperse solid mixture into fractions. Preferably, sizing is carried out according to particle size or particle density. Especially advantageous are dry sieving, wet sieving and air jet sieving, especially air jet sieving, as well as flow sizing, especially by means of air separation.
Within an especially preferred embodiment of the present invention, the composite powder is sized in a first step to preferably remove the coarse fraction of more than 800 μm, preferred of more than 500 μm, especially of more than 250 μm. In this context, dry sieving via a coarse sieve which preferably has a size, i.e. the size of the holes, ranging from 250 μm to 800 μm, preferred ranging from 250 μm to 500 μm, especially of 250 mm, has especially stood the test.
In a further step, the composite powder is preferably sized to preferably remove the fine fraction of <20 μm. In this context, air jet sieving and air separation have turned out to be especially appropriate.
The mean diameters of the particles of the composite powder, the large particles and the small particles, the particle sizes d20, d50, d90 as well as the afore-mentioned lengths are established, according to the invention, appropriately by way of microscopic images, by way of electron-microscopic images, where necessary. For establishing the mean diameters of the large particles and the small particles as well as the particles of the composite powder and for the particle sizes d20, d50, d90 also sedimentation analyses are especially beneficial, with the use of a Sedigraph 5100 (Micromeritics GmbH) being especially useful in this case. For the particles of the composite powder also particle size analyses by laser diffraction have especially proven themselves, in this context the use of a laser diffraction sensor HELOS/F by Sympatec GmbH being especially beneficial. The latter preferably comprises a RODOS dry dispersing system.
Incidentally, these indications as well as all other indications given in the present description refer to a temperature of 23° C., unless otherwise indicated.
The composite powder according to the invention is comparatively compact. Of preference, the share of portions inside the particles of the composite powder having a density of less than 0.5 g/cm3, especially less than 0.25 g/cm3, is less than 10.0%, preferred less than 5.0%, especially less than 1.0%, each related to the total volume of the composite powder.
The percentage by weight of the calcium salt particles, preferably the calcium carbonate particles, preferred of the precipitated calcium carbonate particles, especially the spherical calcium carbonate particles, related to the total weight of the composite powder, preferably amounts to at least 0.1 wt.-%, preferred at least 1.0 wt.-%, especially preferred at least 5.0 wt.-%, and expediently is within the range from 5.0 wt.-% to 80.0 wt.-%, especially preferred within the range from 10.0 wt.-% to 60.0 wt.-%, favorably within the range from 20.0 wt.-% to 50.0 wt.-%. For calcium salt particles, especially for preferably spherical calcium carbonate particles which contain, related to the total quantity of calcium salt particles, especially of preferably spherical calcium carbonate particles, more than 15.0 wt.-% particles having a size of less than 20 μm and/or particles having a size of more than 250 μm, a total quantity of calcium salt particles, especially of preferably spherical calcium carbonate particles within the range from 35.0 wt.-% to 45.0 wt.-% has extraordinarily proven itself. For calcium salt particles, especially for preferably spherical calcium carbonate particles, which, related to the total quantity of calcium salt particles, especially preferably spherical calcium carbonate particles, contain no more than 15.0 wt.-% of particles having a size of less than 20 μm and/or particles having a size of more than 250 μm, a total quantity of calcium salt particles, especially of preferably spherical calcium carbonate particles, within the range from 20.0 wt.-% to 30.0 wt.-% has extraordinarily proven itself.
The percentage by weight of the polymer, preferably of the thermoplastic polymer, related to the total weight of the composition, amounts to preferably at least 0.1 wt.-%, preferred at least 1.0 wt.-%, especially preferred at least 5.0 wt.-%, and expediently ranges from 20.0 wt.-% to 95 wt.-%, preferred from 40.0 wt.-% to 90.0 wt.-%, favorably from 50.0 wt.-% to 80.0 wt.-%.
For a composite powder that contains calcium salt particles, especially preferably spherical calcium carbonate particles, which contain, related to the total quantity of calcium salt particles, especially of preferably spherical calcium carbonate particles, more than 20.0 wt.-% of particles having a size less than 20 μm and/or of particles having a size of more than 250 μm, a total quantity of polymer ranging from 55.0 wt.-% to 65.0 wt.-% has extraordinarily proven itself. For a composite powder that contains calcium salt particles, especially preferably spherical calcium carbonate particles, which contain, related to the total quantity of calcium salt particles, especially of preferably spherical calcium carbonate particles, no more than 20.0 wt.-% of particles having a size of less than 20 μm and/or of particles having a size of more than 250 μm, a total quantity of polymer ranging from 70.0 wt.-% to 80.0 wt.-% has particularly proven itself.
The composite powder excels, inter alia, by excellent bonding of the first material to the second material. The tight bonding of the first material to the second material preferably can be verified by mechanical loading of the composite powder, especially by shaking the composite powder with non-solvent for the polymer and calcium salt particles, especially for the preferably spherical calcium carbonate particles, at 25° C., preferably according to the procedure described in Organikum, 17th Edition, VEB Deutscher Verlag der Wissenschaften, Berlin, 1988, Section 2.5.2.1 “Ausschütteln von Lösungen bzw. Suspensionen (Shaking of solutions and suspensions)”, pp. 56-57. The shaking time preferably is at least one minute, preferably at least 5 minutes, especially 10 minutes, and preferably does not result in a substantial change of form, size and/or composition of the particles of the composite powder. According to the shaking test, especially preferred at least 60 wt.-%, preferably at least 70 wt.-%, preferred at least 80 wt.-%, especially preferred at least 90 wt.-%, favorably at least 95 wt.-%, especially at least 99 wt.-% of the particles of the composite powder are not changed with respect to their composition, their size and preferably their form. A non-solvent especially suited in this context is water, particularly for composite powder containing polyamide.
Furthermore, the particles of the composite powder used according to the invention usually exhibit a comparatively isotropic particulate form which is especially beneficial to applications of the composite powder in SLM methods. The usually almost spherical particulate form of the particles of the composite powder as a rule results in avoiding or at least reducing negative influences such as warpage or shrinkage. Consequently, usually also very advantageous melting and solidifying behavior of the composite powder can be observed.
In contrast to this, conventional powder particles obtained e.g. by cryogenic grinding have an irregular (amorphous) particulate form with sharp edges and corners. Said powders are not advantageous, however, due to their detrimental particulate form and, in addition, due to their comparatively broad particle size distribution and due to their comparatively high fine fraction of particles of <20 μm for SLM methods.
The calcium salt particles, above all the calcium carbonate particles, especially the precipitated calcium carbonate particles, help to specifically influence and control the properties of the polymer, especially of the thermoplastic polymer. In this way, the calcium salt particles, above all the calcium carbonate particles, especially the precipitated calcium carbonate particles, enable proper buffering and pH stabilization of the polymer, especially of the thermoplastic polymer. Moreover, the biocompatibility of the polymer, especially of the thermoplastic polymer, is significantly improved by the calcium salt particles, above all by the calcium carbonate particles, especially by the precipitated calcium carbonate particles. In addition, when the inhibiting calcium carbonate particles are used, significant suppression of the thermal degradation of the polymer, especially of the thermoplastic polymer, is observed.
The said composite powder may be prepared in a way known per se, for example by a single-step method, especially by precipitating or coating, preferably by coating with ground material. Furthermore, even a procedure in which polymer particles are precipitated from a polymer solution which additionally contains small particles in accordance with the invention, preferably in suspended form, is especially suited.
However, a procedure in which polymer particles and calcium salt particles, especially preferably spherical calcium carbonate particles are made to contact one another and are bonded to one another by the action of mechanical forces has especially proven itself. Appropriately, this is carried out in a suitable mixer or in a mill, especially in an impact mill, pin mill or ultra-rotor mill. The rotor speed preferably is more than 1 m/s, preferred more than 10 m/s, especially preferred more than 25 m/s, especially within the range from 50 m/s to 100 m/s.
The temperature at which the composite powder is prepared basically can be freely selected. However, especially advantageous are temperatures of more than −200° C., preferably more than −100° C., preferred more than −50° C., especially preferred more than −20° C., especially more than 0° C. On the other hand, the temperature is advantageously less than 120° C., preferably less than 100° C., preferred less than 70° C., especially preferred less than 50° C., especially less than 40° C. Temperatures ranging from more than 0° C. to less than 50° C., especially ranging from more than 5° C. to less than 40° C. have extraordinarily proven themselves.
Within the scope of an especially preferred embodiment of the present invention, the mixer or the mill, especially the impact mill, the pin mill or the ultra-rotor mill, is cooled during preparation of the composite powder according to the invention to dissipate the energy released. Preferably, cooling is effectuated by a coolant having a temperature of less than 25° C., preferred within the range of less than 25° C. to −60° C., especially preferred within the range of less than 20° C. to −40° C., appropriately within the range of less than 20° C. to −20° C., especially within the range of less than 15° C. to 0° C. Furthermore, the cooling preferably is dimensioned so that at the end of the mixing or grinding operation, preferably of the grinding operation, the temperature in the mixing or grinding chamber, especially in the grinding chamber, is less than 120° C., preferably less than 100° C., preferred less than 70° C., especially preferred less than 50° C., especially less than 40° C.
According to an especially preferred embodiment of the present invention, this procedure results in the fact, especially for polyamides, that the calcium salt particles, especially the preferably spherical calcium carbonate particles, penetrate the interior of the polymer particles and are preferably completely covered by the polymer so that they are not visible from outside. Such particles may be processed and used just as the polymer without the calcium salt particles, especially just as the polymer without the preferably spherical calcium carbonate particles, but they exhibit the improved properties of the said composite powder.
The composite powder is prepared in accordance with the procedure described in the patent application JP62083029 A. A first material (so-called mother particles) is coated on the surface with a second material consisting of smaller particles (so-called baby particles). For this purpose, preferably a surface modifying device (“hybridizer”) is used comprising a high-speed rotor, a stator and a spherical vessel preferably comprising inner knives. The use of NARA hybridization systems preferably having an outer rotor diameter of 118 mm, especially of a hybridization system labeled NHS-0 or NHS-1 by NARA Machinery Co., Ltd., in this context has especially proven itself.
The mother particles and the baby particles are mixed, preferably dispersed and introduced to the hybridizer. There the mixture is preferably continued to be dispersed and preferably repeatedly exposed to mechanical forces, especially impact forces, compressing forces, frictional forces and shear forces as well as the mutual interactions of the particles to uniformly embed the baby particles into the mother particles.
Preferred rotor speeds are within the range from 50 m/s to 100 m/s, related to the circumferential speed.
For further details concerning this method, JP62083029 A is referred to, the disclosure of which including the especially appropriate method variants is explicitly incorporated in the present application by reference.
Within the scope of another especially preferred variant, the composite powder is prepared in accordance with the procedure described in the patent application DE 42 44 254 A1. Accordingly, a method of preparing a composite powder by affixing a substance onto the surface of a thermoplastic material is especially favorable when the thermoplastic material has an average particle diameter of from 100 μm to 10 mm and the substance has a lower particle diameter and better thermal resistance than the thermoplastic material, especially when the method comprises the following steps:
For further details concerning this method, DE 42 44 254 A1 is referred to, the disclosure of which including the especially appropriate method variants is explicitly incorporated in the present application by reference.
Alternatively, the composite powder is prepared in accordance with the procedure described in the patent application EP 0 922 488 A1 and/or in the U.S. Pat. No. 6,403,219 B1. Accordingly, a method of preparing a composite powder by affixing or bonding fine particles to the surface of a solid particle acting as a core by making use of impact and then allowing one or more crystals to grow on the core surface is especially advantageous.
For further details concerning this method, patent application EP 0 922 488 A1 and/or U.S. Pat. No. 6,403,219 B1 is/are referred to, the disclosures of which including the especially appropriate method variants are explicitly incorporated in the present application by reference.
The composite powder may be subjected to fixation in accordance with the procedure described in patent application EP 0 523 372 A1. This procedure is useful especially for a composite powder which was obtained in accordance with the method described in the patent application JP62083029 A. The particles of the composite powder are preferably fixed by thermal plasma spraying, wherein preferably a reduced pressure plasma spraying device is used which preferably has a capacity of at least 30 kW, especially the apparatus described in EP 0 523 372 A1.
For further details concerning this method, patent application EP 0 523 372 A1 is referred to, the disclosure of which including the especially appropriate method variants is explicitly incorporated in the present application by reference.
The composite powder used in the implant according to the invention excels by an excellent property profile suggesting its use especially in laser sintering methods. Its excellent free-flowing property and its excellent flowability during laser sintering enable implants of excellent surface quality and surface finish as well as of improved component density to be produced. At the same time, the composite powder according to the invention exhibits very good shrinking behavior as well as excellent dimensional stability. Moreover, better thermal conductivity can be found outside the laser-treated area.
Moreover, said composite powder exhibits comparatively high isotropy which enables extremely uniform fusing of the composite powder. This behavior may be utilized in SLM processes for producing components of high quality, high component density, low porosity and a small number of defects.
Furthermore, the presence of the calcium salt particles, especially the preferably spherical calcium carbonate particles, in the composite powder enables excellent pH stabilization (buffering) in later applications, especially in those polymers which contain acid groups or are adapted to release acids under certain conditions. These include, for example, polyvinylchloride and polylactic acid.
Moreover, the said composite powder can possibly replace other more expensive materials so as to achieve cost reduction of the final product.
The properties of the composite powder, especially its flowability, can also be controlled via the moisture of the composite powder and can be specifically adjusted as needed. On the one hand, the flowability of the composite powder basically increases with increasing moisture, thus facilitating processability of the composite powder. On the other hand, higher moisture of the composite powder may entail thermal degradation or hydrolysis of the polymer as well as process disruptions especially in the case of thermal processing of the composite powder primarily in the presence of impurities and/or in the presence of very fine particles.
Against this background, the moisture of the said composite powder preferably is less than 2.5 wt.-%, preferred less than 1.5 wt.-%, especially preferred less than 1.0 wt.-%, even more preferred less than 0.9 wt.-%, favorably less than 0.8 wt.-%, expediently less than 0.6 wt.-%, particularly preferred less than 0.5 wt.-%, especially less than 0.25 wt.-%. On the other hand, the moisture of the said composite powder preferably is more than 0.000 wt.-%, preferred more than 0.010 wt.-%, especially more than 0.025 wt.-%.
The use of the inhibiting calcium carbonate in this context enables even further improved thermal processability of the composite powder. The processing window (temperature window) once more is definitely larger than by using conventional calcium carbonate and thermal degradation or hydrolysis of a polymer is once more significantly suppressed.
The desired moisture of the composite powder can be achieved by pre-drying of the composite powder known per se prior to processing, with drying being basically recommended in the production process. For stable process control in this context drying up to a moisture content ranging from 0.01 wt.-% to 0.1 wt.-% has turned out to be especially favorable. Furthermore, the use of a microwave vacuum drier has especially proven itself.
The composite powder may be further processed in a comparatively simple manner as now only one component (the composite powder) and no longer two components (calcium salt particles, especially preferably spherical calcium carbonate particles, and polymer) have to be processed. Problems of dispersion are not observed due to the tight bonding between the polymer and the calcium salt particles, especially the preferably spherical calcium carbonate particles.
Furthermore, the microstructure, the melting behavior and the flow behavior of the composite powder can be specifically controlled by the selection of the fractions and the size of the respective single components. Said properties of the composite powder can be exploited, in turn, to specifically control the final structure of the resulting implants, especially the biocompatibility, the biodegradability and the mechanical properties thereof.
An addition of further processing aids, especially of specific solvents, usually is not required for processing the composite powder. This expands the possible fields of application of the composition especially in the pharmaceutical and food sectors.
The composite powder can be directly used as such. Due to its excellent property profile, the composite powder is especially suited, however, as an additive, especially preferred as a polymer additive, as an addition or starting material for compounding, for the production of implants, for applications in medical engineering and/or in microtechnology and/or for the production of foamed implants. Especially preferred applications in medical engineering include preferably absorbable implants. Especially expedient fields of application comprise injection-molded screws, pressed plates, especially melt-pressed plates, foamed implants as well as flowable powders for selective production methods, in the latter case the total particle size of the particles of the composite powder being preferably less than 3 mm and preferably more than 5.0 μm.
In the form of a polymer additive, the composite powder is preferably added to at least one polymer, especially to a thermoplastic polymer, as matrix polymer. In this case, the polymers which can also be used as a component of the composite powder are especially preferred. To avoid repetitions, therefore the foregoing statements are referred to, especially as regards the preferred forms of the polymer. Extraordinarily preferred matrix polymers include polyvinylchloride (PVC), polyurethane (PU), silicone, polypropylene (PP), polyethylene (PE), especially UHMWPE, and polylactic acid (PLA).
The matrix polymer and the polymer of the composite powder can preferably be mixed at the temperature of use, and especially preferred are chemically identical.
Especially preferred compositions contain 40.0 wt.-% to 99.9 wt.-%, of at least one matrix polymer and 0.1 wt.-% to 50.0 wt.-% of at least one said composite powder.
The production of the composition may be carried out in a manner known per se by mixing the components.
The composition then can be further processed in the usual way, especially granulated, ground, extruded, injection-molded, foamed or else used in 3D printing methods.
Furthermore, the composite powder can be further processed and/or used directly, i.e. without addition of additional polymers.
The advantages of the composite powder can be observed especially when granulating, extruding, injection-molding, melt-pressing, foaming and/or 3D printing the composite powder.
Polymer foams are preferably produced by generating or introducing a gaseous phase to a composition comprising the composite powder and at least one matrix polymer, where necessary. It is the objective to distribute the gas as uniformly as possible within the composition so as to obtain a uniform and homogeneous foam structure. The gas may be introduced in various ways.
Of preference, the gaseous phase is generated by adding a blowing agent. Blowing agents are substances which release gases by chemical reactions (chemical blowing agents) or by phase transition (physical blowing agents). In foam extrusion or in foam injection molding the chemical blowing agent is admixed to the composition in the form of a masterbatch or a physical blowing agent is injected under pressure directly into the melt of the composition. The injection is referred to as direct gassing and is used especially in processing thermoplastic polymers.
Moreover, the said composite powder per se is suited especially for producing implants adapted to replace conventional implants made from metal in the case of bone fractures. The implants serve for fixing the bones until the fracture has healed up. While implants of metal are normally retained in the body or have to be removed by further operation, the implants obtainable from the composite powder according to the invention act as temporary aids. They expediently comprise polymers which the body itself can degrade and substances which provide calcium and valuable phosphorus substances for osteogenesis. The advantages resulting for the patient are obvious: no further operation for removing the implant and accelerated regeneration of the bones.
According to an especially preferred variant of the present invention, the said composite powder is used for producing implants by selective laser sintering. Expediently, particles of the composite powder according to the invention tightly packed next to one another to form a powder bed are locally slightly surface-fused or melted (the polymer only) with the aid of a laser-scanner unit, a directly deflected electron beam or an infrared heating having a mask depicting the geometry. They solidify by cooling due to heat conduction and thus combine to form a solid layer. The powder granules that are not surface-fused remain as supporting material within the component and are preferably removed after completion of the building process. By repeated coating with powder, analogously to the first layer further layers can be solidified and bonded to the first layer.
Types of lasers especially suited for laser sintering methods are all those which cause the polymer of the composite powder according to the invention to sinter, to melt or to crosslink, especially CO2 lasers (10 μm), ND-YAG lasers (1,060 nm), He—Ne lasers (633 nm) or dye lasers (350-1,000 nm). Preferably, a CO2 laser is used.
The energy density in the filling during radiation preferably ranges from 0.1 J/mm3 to 10 J/mm3.
The active diameter of the laser beam preferably ranges from 0.01 nm to 0.5 nm, preferably 0.1 nm to 0.5 nm, depending on the application.
Of preference, pulsed lasers are used, wherein a high pulse frequency, especially from 1 kHz to 100 kHz, has turned out to be particularly suited.
The preferred process can be described as follows:
The laser beam is incident on the uppermost layer of the filling of said material to be used according to the invention and, in so doing, sinters the material at a predetermined layer thickness. Said layer thickness may be from 0.01 mm to 1 mm, preferably from 0.05 mm to 0.5 mm. In this way, the first layer of the desired implant is produced. Subsequently, the working space is lowered by an amount which is less than the thickness of the sintered layer. The working space is filled up to the original height with additional polymer material. By repeated radiation with the laser, the second layer of the implant is sintered and bonded to the preceding layer. By repeating the operation, the further layers are produced until the implant is completed.
The exposure rate during laser scanning preferably amounts to 1 mm/s to 1,000 mm/s. Typically, a rate of about 100 mm/s is applied.
In the present case, for surface-fusing or melting the polymer it has especially proven itself to heat to a temperature within the range from 60° C. to 250° C., preferably within the range from 100° C. to 230° C., especially within the range from 150° C. to 200° C.
The subject matter of the present invention further are implants which are obtainable by selective laser sintering of a composition comprising said composite powder, wherein implants for applications in the field of neuro, oral, maxillary, facial, ear, nose and throat surgery as well as hand, foot, thorax, costal and shoulder surgery are especially preferred.
The percentage of the said composite powder in the composition is preferably at least 50.0 wt.-%, preferred at least 75.0 wt.-%, especially preferred at least 90 wt.-%, especially at least 99.0 wt.-%. Within the scope of a particular embodiment of the present invention, the composition contains exclusively the composite powder according to the invention.
The implants according to the invention appropriately excel by the following properties:
Hereinafter, the present invention shall be further illustrated by plural examples and comparative examples without the inventive idea being intended to be limited in this way.
The mean particle diameter of each of the polylactide granulates 1 to 3 was within the range from 1 to 6 mm.
Within the scope of the present examples, the following variables were established as follows:
Determination of the mechanical properties at injection-molded specimens: Three-point flexural strength and E modulus were determined by means of Texture Analyser TA.XTplus (Stable Micro Systems, Godalming (UK)). The capacity of the load cell used was 50 kg. Exponent 6.1.9.0 software was used. The details of measurement are shown in the following Table 1:
Specimens were produced by HAAKE MiniLab II extruder and, resp., injection molding by HAAKE MiniJet II. The process conditions for specimen production are listed in the following Table 2:
Cytotoxicity Test
The cytotoxicity test (FDA/GelRed) was carried out as follows:
The reference and, resp., negative control used was Tissue Culture Polystyrene (TCPS). 4 replicates were used for each sample and four TCPS (4×) were used for control.
Test Procedure:
A partial medium exchange (1:2) took place on day 2.
The results are listed in Table 3.
Electron Microscope (SEM)
The SEM images were taken by a high-voltage electron microscope (Zeiss, DSM 962) at 15 kV. The samples were sprayed with a gold-palladium layer.
A CO2 gas mixture containing 20% of CO2 and 80% of N2 was introduced to 4 l of calcium hydroxide suspension having a concentration of 75 g/l CaO at an initial temperature of 10° C. The gas flow was 300 l/h. The reaction mixture was stirred at 350 rpm and the reaction heat was dissipated during reaction. Upon abrupt drop of the conductance (drop of more than 0.5 mS/cm/min and decrease of the conductance by more than 0.25 mS/cm within 30 seconds) 0.7% of amino tri(methylene phosphonic acid), based on CaO (as theoretical reference value) is added to the suspension. The reaction into the spherical calcium carbonate particles was completed when the reaction mixture was carbonated quantitatively into spherical calcium carbonate particles, wherein the reaction mixture then showed a pH value between 7 and 9. In the present case, the reaction was completed after about 2 h and the reaction mixture had a pH value of 7 at the reaction end.
The resulting spherical calcium carbonate particles were separated and dried in a conventional way. They showed a mean particle diameter of 12 μm. A typical SEM image is shown in
500 ml of VE (demineralized) water were provided in a 1000 ml beaker. 125 g of spherical calcium carbonate particles according to Example 1 were added under stirring and the resulting mixture was stirred for 5 min. 37.5 g of a 10% sodium metaphosphate (NaPO3)n solution were slowly added and the resulting mixture was stirred for 10 min. 75.0 g of 10% phosphoric acid were slowly added and the resulting mixture was stirred for 20 h. The precipitation is separated and dried in the drying cabinet over night at 130° C. The resulting spherical calcium carbonate particles equally had a mean particle diameter of 12 μm.
A SEM image of the spherical calcium carbonate particles is shown in
A composite powder of spherical calcium carbonate particles and a polylactide (PLLA) was prepared in accordance with the method described in JP 62083029 A using the NHS-1 apparatus. It was cooled with water at 12° C. A polylactide granulate 1 was used as mother particles and the spherical calcium carbonate particles of Example 1 were used as the baby particles (filler).
39.5 g of polylactide granulate were mixed with 26.3 g CaCO3 powder and filled at 6.400 rpm. The rotor speed of the unit was set to 6.400 rpm (80 m/s) and the metered materials were processed for 10 min. The maximum temperature reached in the grinding chamber of NHS-1 was 35° C. A total of 7 repetitions were carried out with equal material quantities and machine settings. A total of 449 g of composite powder was obtained. The composite powder obtained was manually dry-sieved through a 250 μm sieve. The sieve residue (fraction >250 μm) was 0.4%.
A SEM image of the composite powder obtained is shown in
Further composite powders were prepared analogously to Example 3, wherein in Example 5 cooling took place at about 20° C. In each case 30 g of polylactide granulate were mixed with 20 g of CaCO3 powder. The maximum temperature reached within the grinding chamber of NHS-1 was 33° C. for Example 4, 58° C. for Example 5, 35° C. for Example 6 and 35° C. for Example 7. The products were sieved to remove the course fraction >250 μm where possible (manual dry sieving through 250 μm sieve). In the Examples 4, 6 and 7, additionally the fraction <20 μm was classified by flow where possible (by means of air separation) or by sieving (by means of air jet sieving machine). The materials used, the implementation of preparation with or without sieving/air separation as well as the properties of the composite powders obtained are listed in the following Table 3.
The SEM image of the composite powder obtained is shown in
The powder is flowable to a restricted extent (
The SEM image of the composite powder obtained is shown in
The powder is properly flowable and applicable (
The powder layer applied with 500 μm is homogeneous, densely packed, smooth and free from doctor streaks.
Comparison 1
Microstructured composite particles of spherical calcium carbonate particles of Example 1 and an amorphous polylactide (PDLLA) were prepared in accordance with the method described in JP 62083029 A using the NHS-1 apparatus. It was cooled with water at 12° C. A polylactide granulate 3 was used as mother particles and the spherical calcium carbonate particles of Example 1 were used as the baby particles.
39.5 g of polylactide granulate were mixed with 10.5 g of CaCO3 powder and filled at 8,000 rpm. The rotor speed of the unit was set to 8,000 rpm (100 m/s) and the metered materials were processed for 1.5 min. The maximum temperature reached within the grinding chamber of the NHS-1 was 71° C. A total of 49 repetitions was carried out with equal material quantities and machine settings. A total of 2376 g of structured composite particles were obtained. The obtained structured composite particles were manually dry-sieved through an 800 μm sieve for measuring the particle size distribution. The sieve residue (fraction >800 μm) amounted to 47%.
The properties of the microstructured composite particles obtained are listed in the following Table 3.
The SEM analysis illustrates that the surfaces of the structured composite particles are sparsely occupied with spherical calcium carbonate particles and the fragments thereof. As compared to the Examples 3 to 7, the particles show a more irregular particle geometry.
A composite powder of β-tricalcium phosphate particles and a polylactide (PDLLA) was prepared in accordance with the method described in JP 62083029 A using the NHS-1 apparatus. It was cooled with water at 12° C. A polylactide granulate 3 was used as mother particles and β-tricalcium phosphate (β-TCP; d20=30 μm; d50=141 μm; d90=544 μm) was used as baby particles. The SEM image of the β-TCP used is shown in
30.0 g of polylactide granulate were mixed with 20.0 g of β-TCP powder and were filled at 6,400 rpm. The rotor speed of the unit was set to 6,400 rpm (80 m/s) and the metered materials were processed for 10 min. A total of 5 repetitions with equal material quantities and machine settings was carried out. A total of 249 g of composite powder was obtained. The product was sieved to remove the coarse fraction >250 μm where possible (manual dry-sieving through a 250 μm sieve). Then the fine fraction <20 μm was separated through a 20 μm sieve by means of an air jet sieving machine.
A composite powder of rhombohedral calcium carbonate particles and a polylactide (PDLLA) was prepared in accordance with the method described in JP 62083029 A using the NHS-1 apparatus. It was cooled with water at 12° C. A polylactide granulate 3 was used as mother particles and rhombohedral calcium carbonate particles (d20=11 μm; d50=16 μm; d90=32 μm) were used as baby particles.
30.0 g of polylactide granulate were mixed with 20.0 g of the rhombohedral calcium carbonate particles and were filled at 6,400 rpm. The rotor speed of the unit was set to 6,400 rpm (80 m/s) and the metered materials were processed for 10 min. A total of 5 repetitions with equal material quantities and machine settings was carried out. A total of 232 g of composite powder was obtained. The product was sieved to remove the coarse fraction >250 μm where possible (manual dry-sieving through a 250 μm sieve). Then the fine fraction <20 μm was separated through a 20 μm sieve by means of an air jet sieving machine.
A composite powder of ground calcium carbonate particles and a polylactide (PDLLA) was prepared in accordance with the method described in JP 62083029 A using the NHS-1 apparatus. It was cooled with water at 12° C. A polylactide granulate 3 was used as mother particles and ground calcium carbonate (GCC; d20=15 μm; d50=46 μm; d90=146 μm) were used as baby particles.
30.0 g of polylactide granulate were mixed with 20.0 g of GCC and were filled at 6,400 rpm. The rotor speed of the unit was set to 6,400 rpm (80 m/s) and the metered materials were processed for 10 min. A total of 5 repetitions with equal material quantities and machine settings was carried out. A total of 247 g of composite powder was obtained. The product was sieved to remove the coarse fraction >250 μm where possible (manual dry-sieving through a 250 μm sieve). Then the fine fraction <20 μm was separated through a 20 μm sieve by means of an air jet sieving machine.
1At least double-determination
| Number | Date | Country | Kind |
|---|---|---|---|
| 16187906 | Sep 2016 | EP | regional |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/EP2017/070491 | 8/11/2017 | WO |
| Publishing Document | Publishing Date | Country | Kind |
|---|---|---|---|
| WO2018/046238 | 3/15/2018 | WO | A |
| Number | Name | Date | Kind |
|---|---|---|---|
| 8517291 | Rainer et al. | Aug 2013 | B2 |
| 9394428 | Gane et al. | Jul 2016 | B2 |
| 9707734 | Vucak | Jul 2017 | B2 |
| 20040106691 | Monsheimer | Jun 2004 | A1 |
| 20130190441 | Vucak et al. | Jul 2013 | A1 |
| 20140004348 | Vucak et al. | Jan 2014 | A1 |
| 20190308241 | Lundin | Oct 2019 | A1 |
| 20200009297 | Reinauer | Jan 2020 | A1 |
| 20200016826 | Edvinsson | Jan 2020 | A1 |
| 20200307027 | Veregin | Oct 2020 | A1 |
| Number | Date | Country |
|---|---|---|
| 101856514 | Oct 2010 | CN |
| 102 247 624 | Nov 2011 | CN |
| 105031737 | Nov 2015 | CN |
| 2014-508840 | Apr 2014 | JP |
| 2 218 305 | Dec 2003 | RU |
| 2 438 980 | Jan 2012 | RU |
| 2 591 983 | May 2016 | RU |
| WO 2016050119 | May 2006 | WO |
| WO 2012013349 | Feb 2012 | WO |
| WO 2012126600 | Sep 2012 | WO |
| WO 2016057684 | Apr 2016 | WO |
| Entry |
|---|
| Chinese Office Action dated Apr. 1, 2021 from Chinese Application No. 201780055494.5. |
| Japanese Office Action dated Aug. 3, 2021 from Japanese Application No. P2019-512294. |
| International Search Report and Written Opinion dated Jan. 2, 2018 from International Application No. PCT/EP2017/070491. |
| Extended European Search Report dated Feb. 10, 2017 from European Application No. 16 187 906.9. |
| Russian Office Action dated Nov. 3, 2020 from Russian Application No. 2019110367/04 (019939). |
| Russian Search Report dated Oct. 30, 2020 from Russian Application No. 2019110367/04 (019939). |
| Chinese Office Action dated Sep. 18, 2021 from Chinese Application No. 201780055494.5. |
| Number | Date | Country | |
|---|---|---|---|
| 20200009297 A1 | Jan 2020 | US |
