DE102021110336A1 - bone implant material - Google Patents

Abstract

The present invention relates to a bone implant material which emits in the UV-C range and can therefore be used for disinfection in the body.

Description

The present invention relates to inorganic materials that can be used in bone implants or screws.

In order for a bone to grow back together after a fracture, the bone fragments are often stabilized with plates, which in turn are fastened with metal screws, especially in the case of more severe fractures. The plates and screws are made of stainless steel, for example. Alternatively, pure titanium is used for the plates and titanium alloys such as titanium-aluminium-niobium for the screws.

The difficulty with such interventions in the body is that with every invasive intervention there is always the risk of a postoperative complication due to an infection. According to estimates, the probability of infection after the use of an endoprosthesis is between 0.25 - 3%, after the use of osteosynthesis materials even between 5 and 10%. The microorganism Staphylococcus aureus, an endogenous skin bacterium, plays a particularly important role here.

The object is therefore to provide a material by which the risk of infection can be significantly reduced.

This object is solved by a material according to claim 1. Accordingly, a bone implant is proposed, comprising an inorganic material (hereinafter referred to as “inorganic material”), which is able to emit light in a wavelength range of ≧190 nm and ≦290 nm.

Surprisingly, it has been shown that when such a material is used, it is possible in many applications to reduce infections afterwards, since locally limited disinfection or germ inactivation can be achieved in this area (sometimes also called the UV-C area).

• - Die Materialien sind auf einfache Weise aus gut verfügbaren Ausgangsstoffen herstellbar
• - Die Materialien sind biokompatibel und im Körper langzeitstabil
• - Die Materialien sind auf gängige Weise verarbeitbar.
• - Die Materialien sind wasserunlöslich
• - Die Materialien sind strahlungsstabil

For most applications within the present invention, one or more of the following advantages could also be achieved:

• - The materials can be produced in a simple manner from readily available starting materials
• - The materials are biocompatible and long-term stable in the body
• - The materials can be processed in the usual way.
• - The materials are insoluble in water
• - The materials are radiation stable

• - Implantate
• - Prothesen, insbesondere Endoprothesen
• - Platten
• - Schrauben
• - Künstliche Knochen
• - Zahnimplantate
• - Klammern

The term "bone implant" includes and/or means all common materials and devices that are used in all areas of osteosynthesis and endoprosthetics, i.e. in particular (but not limited to):

• - implants
• - Prostheses, in particular endoprostheses
• - Plates
• - screws
• - Artificial bones
• - dental implants
• - brackets

It should be noted that in many applications of the present invention the bone implant consists only partially of the inorganic material, particularly when the bone implant is a plate or screw, for example. In this case it is often preferred that the implant is completely or partially coated with the inorganic material.

The average layer thickness of the coating of the inorganic material is then preferably ≧100 nm and ≦100 μm.

Alternatively, in other applications, the bone implant can consist entirely or essentially of the inorganic material.

The term "substantially" in the sense of the present invention means and/or includes a proportion of ≧95% (% by volume/% by volume), more preferably ≧98% (% by volume/% by volume). %) and most preferably ≥ 99 (v/v %).

The term "inorganic material" means and/or includes in particular materials that contain either no carbon or carbon only in the form of carbonate or bicarbonate.

The term “to emit light in a wavelength range of ≧190 and ≦290 nm” means and/or includes in particular that the material according to the invention has at least one emission band in this wavelength range. The material according to the invention preferably has at least one emission band in the range from ≧200 and ≦280, more preferably from ≧210 and ≦270 nm

According to a preferred embodiment, the inorganic material can be excited by gamma or X-ray radiation, preferably in a wavelength range of ≧10 keV and ≦20 MeV, which means in particular that the inorganic material has an absorption band in this range.

According to a preferred embodiment of the invention, the inorganic material is Ce ³⁺ -, Pr ³⁺ -, Nd ³⁺ -, Bi ³⁺ , Sc ³⁺ -, and/or Gd ³⁺ -doped. This has proven itself in many applications.

The term (as an example) "Pr ³⁺ - doped" is understood in particular to mean that in the material according to the invention praseodymium is present in the (formal) oxidation state +III or (formally) as Pr ³⁺ and substitutes a suitable ion of a lattice material; the same applies to the other ions.

It should be noted that for some materials the ion which is replaced by the dopant is formally in the +II oxidation state - in which case it is then preferred that an additional dopant which is in the +I oxidation state is present to balance the charge. Sodium and/or potassium are particularly preferred here.

The term “lattice material” is understood to mean, in particular, an inorganic host lattice.

According to a preferred embodiment, the inorganic material contains Ce ³⁺ -, Pr ³⁺ -, Nd ³⁺ -, Bi ³⁺ -, Sc ³⁺ -, and/or Gd ³⁺ - stoichiometrically.

According to a preferred embodiment, the material according to the invention comprises as a lattice material a material selected from phosphates, more complex polyphosphates, in particular materials containing P ₃ O ₉ ³ or P ₅ O ₁₄ ³ - ions, silicates, more complex silicates, in particular materials containing Si _x O _y ^n- - ions (with x = 2 to 10, y = 4 to 30 and n of the resulting negative charge from 3 to 12), phosphosilicates, or mixtures thereof, it preferably consists essentially of them. Phosphates and silicates are particularly preferred.

The degree of doping is preferably >0 and ≦10%, preferably ≧0.01% and ≦5% and most preferably ≧0.1% and ≦1%.

A degree of doping of [X]% is understood to mean that [X]% of the sum of all ions to be replaced in the undoped material are replaced by the doping metal or metals in the material according to the invention.

According to a preferred embodiment, the material according to the invention comprises a material selected from the group consisting of YPO ₄ : Nd, LuPO ₄ : Nd, ScPO ₄ , LuPO ₄ : Sc, YPO ₄ : Sc, LaPO ₄ : Pr, Sr ₃ (PO ₄ ) ₂ :Pr,Na, YPO ₄ :Pr, YPO ₄ :Pr,Nd, LuPO ₄ :Pr, LuPO ₄ :Pr,Nd, NaMgPO ₄ :Pr, KSrPO ₄ :Pr, LiCaPO ₄ :Pr, Ca ₉ Y(PO ₄ ) ₇ :Pr, _Ca9Lu (PO4) ₇ :Pr, _Ca5 ( _{PO4 ) 2SiO4} :Pr,Na, _Sr5 ( _{PO4 ) 2SiO4} : _Pr ,Na, _Lu2SiO5 : _Pr , Lu ₂ Si ₂ O ₇ :Pr, ScPO ₄ :Bi
or mixtures thereof, preferably consisting essentially of it.

Emission maxima of these materials are listed in the table below: Table 1: Emission maxima of some preferred inorganic materials according to the invention. material Emission wavelength/nm YPO ₄ :Nd 193 LuPO ₄ :Nd 193 ScPO ₄ 205 LuPO ₄ :Sc 224 YPO ₄ :Sc 225 LaPO ₄ :Pr 225 ScPO ₄ :Bi 230 Sr ₃ (PO ₄ ) ₂ :Pr,Na 231 YPO ₄ :Pr 233 YPO ₄ :Pr,Nd 233 LuPO ₄ :Pr 233 LuPO ₄ :Pr,Nd 233 NaMgPO ₄ :Pr 235 KSrPO ₄ :Pr 235 _LiCaPO4 :Pr 240 Ca ₉ Y(PO ₄ ) ₇ :Pr 250 Ca ₉ Lu(PO ₄ ) ₇ :Pr 250 Ca ₅ (PO ₄ ) ₂ SiO ₄ :Pr,Na 260 Sr ₅ (PO ₄ ) ₂ SiO ₄ :Pr,Na 260 _Lu2SiO5 : _Pr 270 _{Lu2Si2O7 : Pr} 270

According to a preferred embodiment of the invention, the inorganic material is partly, preferably essentially, ceramic or consists partly, preferably essentially, of a ceramic.

The term "ceramic" in the sense of the present invention means and/or includes in the sense of the present invention in particular a compact crystalline or polycrystalline material with a controlled amount of pores or non-porous.

The expression "polycrystalline material" in the sense of the present invention means and/or includes in particular a material with a volume density of more than 90 percent of the main component, consisting of more than 80 percent of individual crystal domains, each crystal domain having a diameter of 0.1 - 20 µm and has a different crystallographic orientation. The individual crystal domains can be connected or diluted with one another via amorphous or glass-like material or via additional crystalline phases.

According to a preferred embodiment of the present invention, the crystalline material has a density of ≧90% to ≦100% of the theoretical density. This has proven advantageous for many applications of the present invention.

The present invention also relates to the use of an inorganic material in bone implants to reduce the risk of infection and/or for sterilization and/or disinfection in the body.

The aforementioned components, as well as those to be used according to the invention that are claimed and described in the exemplary embodiments, are subject in terms of their size, shape, choice of material and technical design no special exceptional conditions, so that the selection criteria known in the field of application can be applied without restriction.

• 1 ein Emissionsspektrum eines ersten erfindungsgemäßen anorganischen Materials;
• 2 einen Ausschnitt des Spektrums aus 1 sowie der relativem spektralem Desinfektionseffizienz für B. Subtilis nach DIN 5031-10
• 3 ein Emissionsspektrum eines zweiten erfindungsgemäßen anorganischen Materials;
• 4 vier Emissionsspektren eines dritten erfindungsgemäßen anorganischen Materials bei unterschiedlichen Röntgenanregungen; sowie
• 5 vier Emissionsspektrum eines vierten erfindungsgemäßen anorganischen Materials bei unterschiedlichen Röntgenanregungen.

Further details, features and advantages of the subject of the invention result from the subclaims and from the following description of the accompanying drawing, in which - by way of example - several embodiments of the device according to the invention are shown, as well as the following examples, which are purely illustrative and not limiting are to be seen. In the drawings shows:

• 1 an emission spectrum of a first inorganic material according to the invention;
• 2 a section of the spectrum 1 and the relative spectral disinfection efficiency for B. subtilis according to DIN 5031-10
• 3 an emission spectrum of a second inorganic material according to the invention;
• 4 four emission spectra of a third inorganic material according to the invention with different X-ray excitations; such as
• 5 four Emission spectrum of a fourth inorganic material according to the invention with different X-ray excitations.

The invention is further illustrated by the following examples, which are to be considered purely descriptive and not limiting:

Example I

• Die pulverförmigen Edukte Pr₆O₁₁ (99,99 %, Treibacher), NH₄H₂PO₄ (≥99,0 %, Merck KGaA), SrCO₃ (99,9 %, Dr. Paul Lohmann) und SiO₂ (>99,8 %, Aerosil 300, Evonik AG) wurden unter Zugabe von einigen Millilitern Isopropanol in einem Achatmörser gründlich zu einer homogenen Mischung vermahlen. Nachdem das Isopropanol vollständig verdampft war, wurden die entstandenen Mischungen in Korundtiegel überführt und 2 Stunden bei 800 °C an Luft geheizt. Das resultierende weiße Pulver wurde erneut gemahlen und 3 Stunden lang bei 1250 °C unter reduzierender Atmosphäre (5/95 % H₂/N₂) in einem Korundtiegel kalziniert. Das erhaltene weiße Pulver wurde mittels P-XRD untersucht und nach einem Abgleich mit einem Referenzspektrum, entnommen aus „Pearsons Crystal Database“ (PCD-Eintrag Nr.: 1936482) als phasenreines Sr₃(PO₄)₂ identifiziert.

Example I relates to Sr ₃ (PO ₄ ) ₂ :Pr,S ₁ prepared as follows:

• The powdered starting materials Pr ₆ O ₁₁ (99.99%, Treibacher), NH ₄ H ₂ PO ₄ (≥99.0%, Merck KGaA), SrCO ₃ (99.9%, Dr. Paul Lohmann) and SiO ₂ ( >99.8%, Aerosil 300, Evonik AG) were thoroughly ground to a homogeneous mixture in an agate mortar with the addition of a few milliliters of isopropanol. After the isopropanol had evaporated completely, the resulting mixtures were transferred to corundum crucibles and heated in air at 800° C. for 2 hours. The resulting white powder was ground again and calcined for 3 hours at 1250°C in a reducing atmosphere (5/95% H ₂ /N ₂ ) in a corundum crucible. The white powder obtained was analyzed by P-XRD and identified as phase-pure Sr ₃ (PO ₄ ) ₂ after comparison with a reference spectrum taken from "Pearson's Crystal Database" (PCD entry no.: 1936482).

1 shows the emission spectrum of the material under X-ray excitation (50 kV and 1.92 mA), 2 a section of the spectrum, behind it (in gray) is the relative spectral disinfection efficiency for B. subtilis according to DIN 5031-10. As can be seen, the material emits in an area where disinfection is possible.

Example II

• Die pulverförmigen Edukte Lu₂O₃ (mind. 99,99%), Pr₆O₁₁ (99,99 %, Treibacher), Nd₂O₃ (Treibacher, mind. 99 %) wurden in einem 100 ml Einhalsrundkolben in 50 ml dest. H₂O und 1,78 ml H₃PO₄ (85 %) suspendiert. Dann wurde die Suspension für 24 h gerührt und anschließend der Einhalsrundkolben in den Trockenschrank gestellt, bis das Wasser vollständig verdampft war. Das getrocknete Pulver wurde ausgewogen, gemörsert und mit 2 Gew.-% LiF (Aldrich Chemical Company) sowie 3,42 Gew.-% NH₄H₂PO₄ (≥99,0 %, Merck KGaA) - beides bezogen auf die Auswaage - homogenisiert. Diese Mischung wurde in einen Korundtiegel überführt und 4 Stunden bei 1000 °C unter CO-Atmosphäre reduzierend geheizt. Zum Schluss wurde das Material in HNO₃/H₂O (1:7) bei 60 °C für 5 Stunden gerührt und bis zur pH-Neutralität mit dest. H₂O gewaschen. Das erhaltene Pulver wurde mittels P-XRD untersucht und nach einem Abgleich mit einem Referenzspektrum, entnommen aus „Pearsons Crystal Database“ (ICDD-Eintrag Nr.: 04-002-6024) als phasenreines LuPO₄ identifiziert.

Example II relates to LuPO ₄ :Nd,Pr, which was prepared as follows:

• The powdered starting materials Lu ₂ O ₃ (min. 99.99%), Pr ₆ O ₁₁ (99.99%, Treibacher), Nd ₂ O ₃ (Treibacher, min. 99%) were placed in a 100 ml single-necked round bottom flask in 50 ml least H ₂ O and 1.78 ml H ₃ PO ₄ (85%) suspended. Then the suspension was stirred for 24 h and then the one-neck round bottom flask was placed in the drying cabinet until the water had completely evaporated. The dried powder was weighed out, ground in a mortar and mixed with 2% by weight LiF (Aldrich Chemical Company) and 3.42% by weight NH ₄ H ₂ PO ₄ (≧99.0%, Merck KGaA)—both based on the final weight - homogenized. This mixture was transferred to a corundum crucible and heated in a reducing manner at 1000° C. under a CO atmosphere for 4 hours. Finally, the material was stirred in HNO ₃ /H ₂ O (1:7) at 60° C. for 5 hours and diluted with dist. _H2O washed. The powder obtained was examined by P-XRD and identified as phase-pure LuPO ₄ after comparison with a reference spectrum taken from "Pearson's Crystal Database" (ICDD entry no.: 04-002-6024).

3 shows the emission spectrum of the material under X-ray excitation (50 kV and 1.7 mA).

Example III:

• Die pulverförmigen Edukte La₂O₃ (mind. 99,99%), Pr₆O₁₁ (99,99 %, Treibacher), wurden in einem 100 ml Einhalsrundkolben in 50 ml dest. H₂O und 1,78 ml H₃PO₄ (85 %) suspendiert. Dann wurde die Suspension für 24 h gerührt und anschließend der Einhalsrundkolben in den Trockenschrank gestellt, bis das Wasser vollständig verdampft war. Das getrocknete Pulver wurde ausgewogen, gemörsert und mit 2 Gew.-%* LiF (Aldrich Chemical Company) sowie 3,42 Gew.-%* NH₄H₂PO₄ (≥99,0 %, Merck KGaA) homogenisiert. Diese Mischung wurde in einen Korundtiegel überführt und 4 Stunden bei 1000 °C unter CO-Atmosphäre reduzierend geheizt. Zum Schluss wurde das Material in HNO₃/H₂O (1:7) bei 60 °C für 5 Stunden gerührt und bis zur pH-Neutralität mit dest. H₂O gewaschen. Das erhaltene Pulver wurde mittels P-XRD untersucht und nach einem Abgleich mit einem Referenzspektrum als phasenreines LaPO₄ identifiziert.

Example III refers to LaPO ₄ :Pr, which was prepared as follows:

• The powdered starting materials La ₂ O ₃ (at least 99.99%), Pr ₆ O ₁₁ (99.99%, Treibacher) were dissolved in 50 ml dist. H ₂ O and 1.78 ml H ₃ PO ₄ (85%) suspended. Then the suspension was stirred for 24 h and then the one-neck round bottom flask was placed in the drying cabinet until the water had completely evaporated. The dried powder was weighed out, ground in a mortar and homogenized with 2% by weight* LiF (Aldrich Chemical Company) and 3.42% by weight* NH ₄ H ₂ PO ₄ (≧99.0%, Merck KGaA). This mixture was transferred to a corundum crucible and heated in a reducing manner at 1000° C. under a CO atmosphere for 4 hours. Finally, the material was stirred in HNO ₃ /H ₂ O (1:7) at 60° C. for 5 hours and diluted with dist. _H2O washed. The powder obtained was examined by P-XRD and identified as phase-pure LaPO ₄ after comparison with a reference spectrum.

4 shows four emission spectra of the material at different X-ray excitations.

Example IV:

• Die pulverförmigen Edukte Y₂O₃ (mind. 99,99%), Pr₆O₁₁ (99,99 %, Treibacher), wurden in einem 100 ml Einhalsrundkolben in 50 ml dest. H₂O und 1,78 ml H₃PO₄ (85 %) suspendiert. Dann wurde die Suspension für 24 h gerührt und anschließend der Einhalsrundkolben in den Trockenschrank gestellt, bis das Wasser vollständig verdampft war. Das getrocknete Pulver wurde ausgewogen, gemörsert und mit 2 Gew.-%* LiF (Aldrich Chemical Company) sowie 3,42 Gew.-%* NH₄H₂PO₄ (≥99,0 %, Merck KGaA) homogenisiert. Diese Mischung wurde in einen Korundtiegel überführt und 4 Stunden bei 1000 °C unter CO-Atmosphäre reduzierend geheizt. Zum Schluss wurde das Material in HNO₃/H₂O (1:7) bei 60 °C für 5 Stunden gerührt und bis zur pH-Neutralität mit dest. H₂O gewaschen. Das erhaltene Pulver wurde mittels P-XRD untersucht und nach einem Abgleich mit einem Referenzspektrum als phasenreines YPO₄ identifiziert.

Example IV relates to YPO ₄ :Pr made as follows:

• The powdery starting materials Y ₂ O ₃ (at least 99.99%), Pr ₆ O ₁₁ (99.99%, Treibacher) were dissolved in 50 ml dist. H ₂ O and 1.78 ml H ₃ PO ₄ (85%) suspended. Then the suspension was stirred for 24 h and then the one-neck round bottom flask was placed in the drying cabinet until the water had completely evaporated. The dried powder was weighed out, ground in a mortar and homogenized with 2% by weight* LiF (Aldrich Chemical Company) and 3.42% by weight* NH ₄ H ₂ PO ₄ (≧99.0%, Merck KGaA). This mixture was transferred to a corundum crucible and heated in a reducing manner at 1000° C. under a CO atmosphere for 4 hours. Finally, the material was stirred in HNO ₃ /H ₂ O (1:7) at 60° C. for 5 hours and diluted with dist. _H2O washed. The powder obtained was examined by P-XRD and identified as phase-pure YPO ₄ after comparison with a reference spectrum.

5 shows four emission spectra of the material at different X-ray excitations.

Claims (10)

Bone implant comprising an inorganic material capable of emitting light in a wavelength range of ≥ 190 nm and ≤ 290 nm. Bone implant according claim 1 , wherein the implant is completely or partially coated with the inorganic material. Bone implant according claim 1 , wherein the implant consists essentially of the inorganic material. Bone implant according to one of Claims 1 until 3 , wherein the inorganic material is Ce ³⁺ -, Pr ³⁺ -, Bi ³⁺ -, Nd ³⁺ -, Sc ³⁺ -, and/or Gd ³⁺ -doped. Bone implant according to one of Claims 1 until 4 , where the degree of doping is > 0 and ≤ 10%. Bone implant according to one of Claims 1 until 5 , wherein the inorganic material as a lattice material is a material selected from phosphates, more complex polyphosphates, in particular materials containing P ₃ O ₉ ^3- or P ₅ O ₁₄ ^3- ions, silicates, more complex silicates, in particular materials containing Si _x O _y ⁿ - ions (with x = 2 to 10, y = 4 to 30 and n the resulting negative charge from 3 to 12) contain phosphosilicates, or mixtures thereof. Bone implant according to one of Claims 1 until 6 , wherein the material according to the invention is a material selected from the group consisting of YPO ₄ :Nd, LuPO ₄ :Nd, ScPO ₄ , LuPO ₄ :Sc, YPO ₄ :Sc, LaPO ₄ :Pr, Sr ₃ (PO ₄ ) ₂ :Pr, Na, YPO ₄ :Pr, YPO ₄ :Pr,Nd, LuPO ₄ :Pr, LuPO ₄ :Pr,Nd, NaMgPO ₄ :Pr, KSrPO ₄ :Pr, LiCaPO ₄ :Pr, Ca ₉ Y(PO ₄ ) ₇ :Pr, Ca ₉ Lu(PO ₄ ) ₇ :Pr, Ca ₅ (PO ₄ ) ₂ SiO ₄ :Pr,Na, Sr ₅ (PO ₄ ) ₂ SiO ₄ :Pr,Na, Lu ₂ SiO ₅ :Pr, Lu ₂ Si ₂ O ₇ :Pr, ScPO ₄ :Bi or mixtures thereof Bone implant according to one of Claims 1 until 7 , wherein the inorganic material is present at least partially as a ceramic Bone implant according to one of Claims 1 until 8th , selected from the following group containing: - implants - prostheses, in particular endoprostheses - plates - screws - artificial bones - dental implants - clips Use of an inorganic material capable of emitting light in a wavelength range of ≧190 nm and ≦290 nm in bone implants to reduce the risk of infection and/or for sterilization and/or disinfection in the body

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