JP2015136553A - Bone restoration material using peek as base material and method for producing the same - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a bone restoration material having an elastic modulus close to that of a bone with PEEK as a base material, and in which the surface layer has high apatite organization properties.SOLUTION: Provided is a bone restoration material comprising: a base material made of polyether ether ketone (PEEK); and a surface layer made of titanium oxide and stuck to the prescribed part of the surface in the base material by a chemical bond via an oxycarbonyl (-O-C=O) group or the irregularity engagement of particles, and the surface layer has a zeta potential of +3 mV to +20 mV in a neutral aqueous solution.

Description

  The present invention relates to a bone repair material based on polyetheretherketone (PEEK) and a method for producing the same. The bone repair material of the present invention can be suitably used for bone repair in a portion where a large load is applied in the body.

  Currently, titanium metal or an alloy thereof is mainly used as a material for bone repair in a portion to which a large load is applied in the body. Since these metals have a much higher modulus of elasticity than bone tissue, they are made of porous material so that no abnormal stress is generated in the surrounding bone, and the porosity and pore diameter are controlled appropriately. Is done.

  In recent years, PEEK having an elastic modulus close to that of bone has been put into practical use as an intervertebral spacer, for example. And since PEEK itself does not couple | bond with a bone, the connectivity with the surrounding bone is provided by filling and inserting an autologous bone in the space | gap part which an intervertebral spacer has.

  Furthermore, in order to impart bone-binding properties to PEEK without using autologous bone, for example, the surface of the PEEK base material is activated by chemical treatment such as NaOH treatment (Non-patent Document 1), and PEEK powder is bioactive ceramics. To form a composite material (Non-patent Documents 2 and 3, Patent Documents 1 and 2), and dipping the PEEK base material in an aqueous solution containing calcium ions and / or phosphate ions to form hydroxyapatite on the surface of the base material (E.g., non-patent document 4 and patent document 3-5), a PEEK base material is immersed in a liquid in which a bioactive substance such as calcium phosphate is suspended, and the bioactive substance is deposited on the surface thereof. By heating this at the glass transition temperature or higher and below the melting point, the bioactive substance is fixed to the PEEK base material (Patent Document 6), and apatite is plasma sprayed on the PEEK base material (Non-Patent Document 5). Apatite cold spray (Non-patent Document 6), a variety of methods such as forming a titanium oxide on the surface of the PEEK substrate (Non-Patent Document 7) have been reported by arc ion plating.

JP 2010-35827 A JP 2011-78624 A JP 2008-245775 A JP 2009-34302 A JP 2009-611045 A JP 2013-22234 A

Pino et al. Acta Biomat, vol.4, p1827-1836 (2008) Kim et al., Biomater Appl, vol.24, p105-118 (2009) Shucong et al., Biomaterials, vol.226, p2343-2352 (2005) Ha et al., J Mater Sci: Mater Med, vol. 8, p683-690 (1997) Ha et al., J Mater Sci: Mater Med, vol. 5, p481-484 (1994) Lee et al. Acta Biomat, vol. 9, p6177-6187 (2013) Tsou H-K et al., Surf Coat Tech, vol.204, p1121-1125 (2009)

  However, the method of filling the autologous bone not only invades a normal site in order to extract the autologous bone, but also the fixation of the intervertebral spacer is not sufficient. According to the method described in Non-Patent Document 1, even if a high-concentration NaOH aqueous solution is used, it is not possible to provide PEEK with an apatite-forming ability that is high enough to be practically satisfactory. In the methods described in Non-Patent Documents 2 and 3 or Patent Documents 1 and 2, a large amount of bioactive ceramic powder must be mixed in order to obtain a high apatite-forming ability, and the mechanical strength of the composite material decreases accordingly. To do. In the methods described in Non-Patent Document 4 and Patent Documents 3-5, only calcium phosphate is deposited on the surface of the PEEK base material. Therefore, the calcium phosphate layer may be peeled off during storage or in the body. poor. In the material obtained by the method described in Patent Document 6, since the coverage of the PEEK base material surface with a bioactive substance is 50% or less, a high bone bonding force cannot be obtained. In the method described in Non-Patent Document 5, the PEEK base material may be thermally denatured during thermal spraying. The method described in Non-Patent Document 6 does not give an apatite layer firmly fixed to a PEEK base material. The method described in Non-Patent Document 7 requires a special and expensive apparatus, and titanium oxide does not exhibit apatite forming ability as it is.

  Therefore, an object of the present invention is to provide a bone repair material having an elastic modulus close to that of bone using PEEK as a base material and having a high surface layer apatite forming ability.

In order to solve the problem, the bone repair material of the present invention is
A substrate made of polyetheretherketone (PEEK);
A surface layer made of titanium oxide and fixed to a predetermined portion of the surface of the substrate;
The surface layer has a positive zeta potential in a neutral aqueous solution.
Here, whether or not the surface layer has a positive zeta potential in a neutral aqueous solution can be confirmed by measuring the zeta potential in a neutral solution containing an electrolyte such as sodium chloride. The electrolyte concentration at this time is suitably about 10 mM for sodium chloride, but is not limited.

  Since this base material is made of PEEK, this bone repair material has a tensile strength equal to or higher than that of bone and an elastic modulus close to that of bone. Therefore, abnormal stress is not generated in the surrounding bone in the implanted state, and the patient can spend comfortably in comfort. In addition, a surface layer made of titanium oxide is provided at a predetermined site on the surface of the substrate, and the surface layer has a positive zeta potential in a neutral aqueous solution, so that apatite is formed on the surface layer even in vivo. To be combined with bone. The surface layer is provided at a position where it is desired to bond with the bone according to the bone defect situation. For example, when the bone repair material is implanted in a vertebral body defect, the predetermined part is a part facing the defect.

Suitable methods for producing the bone repair material of this invention include:
A surface layer forming step of preparing a base material made of polyether ether ketone and forming a surface layer made of titanium oxide at a predetermined portion of the base material surface;
An acid treatment step of bringing an acid into contact with the surface layer is sequentially performed.

  A metal oxide such as titanium oxide has an OH group as its surface is hydrated in water. Commonly speaking, when the pH of the water of the dispersion medium is lower than 7, protons are added to the OH groups and positively charged. When the pH is higher than 7, protons are extracted from the OH groups and charged negatively. . However, the surface of the acid-treated titanium oxide is positively charged even in a neutral aqueous solution and exhibits high apatite forming ability.

  As described above, in the bone repair material of the present invention, the PEEK base material exhibits an elastic modulus close to that of living bone, and the surface titanium oxide layer has a positive potential in body fluid and exhibits excellent apatite forming ability. Therefore, it is stably fixed to the surrounding bone without causing abnormal stress in the surrounding bone tissue.

2 is an X-ray photoelectron (XPS) spectrum of an untreated PEEK substrate (Comparative Example 1), an O ₂ plasma treated PEEK substrate (Example 1) and a UV treated PEEK substrate (Example 2).

  The potential in the neutral aqueous solution of the surface layer is preferably +3 mV or more and +20 mV or less. This is because if it is less than +3 mV, the apatite-forming ability is slightly poor, and it is practically difficult to charge it to exceed +20 mV.

  One preferable form of fixing between the surface layer and the predetermined portion is a chemical bond between the titanium oxide and the polyether ether ketone. This is because the two are firmly bonded to each other, and there is almost no possibility that the surface layer is peeled off during use in a living body. When the titanium oxide is in a gel form and the polyether ether ketone has a hydrophilic group at its molecular end, the chemical bond may be through the hydrophilic group.

  And when the said titanium oxide makes gel form, the preferable thickness of the said surface layer is 0.5 micrometer-10 micrometers. This is because manufacturing outside this range is difficult. That is, if the thickness is less than 0.5 μm, it is necessary to operate with great care so that the surface layer does not disappear in, for example, an acid treatment step described later for positively charging. On the other hand, if it exceeds 10 μm, for example, in the gelation step described later, it is necessary to operate remarkably carefully so that the surface layer does not crack.

  Another preferable form of fixing between the surface layer and the predetermined portion is that the titanium oxide is in the form of particles and the particles bite into the substrate. This is because both the surface layer and the base material are firmly bonded to each other without chemically changing, and the surface layer hardly peels off during use in vivo. The particles are exposed from the surface of the substrate except for the portion that bites into the substrate, and apatite is formed in the exposed portion. A preferable average particle diameter of the titanium oxide particles is 1 μm or more and 1 mm or less. If it is less than 1 μm, it is difficult to bite in, and if it exceeds 1 mm, the surface becomes too rough and may damage surrounding tissues in the living body. A particularly preferable average particle diameter is 3 μm or more and 100 μm or less.

  As described above, the surface layer may be composed of either gel-like titanium oxide or particulate titanium oxide, or may be a combination of both. One example of the combination is a laminated structure of an inner layer made of particulate titanium oxide and an outer layer made of gelled titanium oxide that uniformly covers the inner layer, and a part of the titanium oxide particles constituting the inner layer are The surface layer is fixed to the predetermined portion by biting into the base material while being exposed from the surface of the base material. Since the chemical species constituting the inner layer and the outer layer are both titanium oxide, the inner layer and the outer layer are strongly fixed by a chemical bond between oxygen and titanium.

  Even when the surface layer has such a laminated structure, the preferred average particle diameter of titanium oxide constituting the inner layer is 1 μm or more and 1 mm or less, and the preferred thickness of the titanium oxide constituting the outer layer is 0.5 μm to 10 μm. It may be.

  The acid used in the acid treatment step is preferably one or more aqueous solutions selected from hydrochloric acid, nitric acid, and sulfuric acid, and has a concentration of 0.01M to 5M. A particularly preferable concentration is 0.1 M to 0.5 M. When the acid treatment is performed within this range, the surface layer can be charged to +3 mV to +20 mV in a relatively short time.

One preferred surface layer forming step for constituting the surface layer with gelled titanium oxide is:
There are two sub-steps: a step of forming a hydrophilic group at the predetermined portion, and a step of bringing the sol of titanium oxide into contact with the same portion and gelling the sol. The titanium oxide sol can be easily obtained by hydrolyzing a titanium alkoxide such as titanium tetraisopropoxide. And gelation begins with polycondensation after hydrolysis. Therefore, gelation is accelerated by evaporating water by heating the sol.
Since PEEK is essentially hydrophobic, a titanium oxide sol can be brought into contact with and attached to the site by forming a hydrophilic group in advance at the site where the surface layer is to be formed. Accordingly, simultaneously with gelation, the gel is firmly bonded to PEEK via the hydrophilic group.

  The hydrophilic group may be an oxycarbonyl (—O—C═O) group or a carbonyl (—C═O) group. In the case of an oxycarbonyl (—O—C═O) group or a carbonyl (—C═O) group, the PEEK substrate is easily formed by plasma treatment or ultraviolet irradiation in an oxygen atmosphere. The preferable time of plasma treatment or UV irradiation is 30 seconds or more or 5 minutes or more, respectively, and particularly preferably 5 minutes or more or 30 minutes or more, respectively.

  One preferable surface layer forming step for forming the surface layer with particulate titanium oxide is a projecting step of projecting titanium oxide particles onto the predetermined portion. When the titanium oxide particles are projected onto the surface of the substrate at a high pressure, the particles bite to a depth corresponding to the particle size and pressure, and the substrate and the particles engage with each other. Thereby, a base material and particle | grains are couple | bonded firmly. When the particles have an average particle size in the above range, they uniformly bite into the substrate surface.

  One preferable surface layer forming step for forming the surface layer as a laminated structure of the inner layer and the outer layer is a step of projecting titanium oxide particles to the predetermined portion, and then the same portion and / or the projected titanium oxide particles. And a step of bringing the sol of titanium oxide into contact with the gel.

[Production conditions]
Example 1
A PEEK disk having a size of φ12 mm × thickness 3 mm was polished with # 800 SiC abrasive paper, ultrasonically washed with 2-propanol for 30 minutes, then washed with ultrapure water, and dried with a dryer. . This PEEK disc was treated using a plasma polymerization system PD-2S manufactured by Samco International under the conditions of an oxygen partial pressure of 50 Pa, a gas flow rate of 30 cm ³ / min, an anode-substrate distance of 25 mm, and a treatment time of 5 minutes (hereinafter referred to as “the following”) "O ₂ plasma treatment").

Next, a solution A in which 0.01 mol of titanium tetraisopropoxide (TTIP) and 0.185 mol of ethanol (EtOH) are mixed, 0.01 mol of water (H ₂ O), 0.185 mol of ethanol and concentrated nitric acid (HNO ₃ ) 0 A solution B mixed with 0.001 mol was prepared, and the solution B was gradually added dropwise to the solution A while stirring to prepare a titanium oxide sol (the molar ratio of the components in the sol was TTIP: H ₂ O: EtOH). : HNO ₃ = 1: 1: 37: 0.1). The PEEK disk treated with O ₂ plasma in this sol was submerged at a rate of 1 cm / min, pulled up at a rate of 1 cm / min, and then heated at 80 ° C. for 24 hours in a dry atmosphere (hereinafter referred to as “sol-gel coating treatment”). That said.)
Thereafter, the PEEK disk was immersed in 0.1 M hydrochloric acid at 80 ° C. for 24 hours (hereinafter referred to as “acid treatment”) and washed with ultrapure water for 30 seconds.

-Example 2-
In Example 1, instead of the O ₂ plasma treatment, the UV light source (output 5.2 mW / cm ² , wavelength 254 nm + 185 nm) attached to the UV ozone cleaner UV253 manufactured by Philgen Corporation was used for about 30 minutes. Samples were prepared under the same conditions as in Example 1.
Example 3
In Example 1, a sample was produced under the same conditions as in Example 1 except that the concentration of hydrochloric acid used in the acid treatment was 0.01M.
Example 4
In Example 1, a sample was produced under the same conditions as in Example 1 except that the temperature of hydrochloric acid used for the acid treatment was 70 ° C.
-Example 5
In Example 1, a sample was produced under the same conditions as in Example 1 except that the acid treatment time was 18 hours.
-Example 6
In Example 1, a sample was produced under the same conditions as in Example 1 except that the solution used for the acid treatment was 0.1 M nitric acid.
-Example 7-
In Example 1, a sample was produced under the same conditions as in Example 1 except that the solution used for the acid treatment was changed to 0.1 M sulfuric acid.

-Example 8-
A PEEK disk having a size of φ12 mm × thickness 3 mm was polished with # 800 SiC abrasive paper, ultrasonically washed with 2-propanol for 30 minutes, then washed with ultrapure water, and dried with a dryer. . Titanium oxide HT0100 (average particle size 3.6 μm, rutile phase) manufactured by Toho Titanium was projected onto this PEEK disk for 30 seconds at a pressure of 0.5 MPa and a nozzle-substrate distance of 10 mm (hereinafter referred to as “projection treatment”). Then, after ultrasonically washing with 2-propanol for 30 minutes, it was washed with ultrapure water and dried with a dryer.
Then, it was immersed in 2M hydrochloric acid at 80 ° C. for 24 hours and washed with ultrapure water for 30 seconds.

-Example 9-
In Example 8, a sample was produced under the same conditions as in Example 8 except that the concentration of hydrochloric acid used in the acid treatment was 0.01M.
-Example 10-
In Example 8, a sample was produced under the same conditions as in Example 8 except that the temperature of the solution used for the acid treatment was 30 ° C.
-Example 11-
In Example 8, a sample was produced under the same conditions as in Example 8 except that the acid treatment time was 0.1 hour.
-Example 12-
After the projection treatment under the same conditions as in Example 8, a sol-gel coating treatment and an acid treatment were performed under the same conditions as in Example 1 to produce a sample.

-Comparative Example 1-
In Example 1, a sample was manufactured under the same conditions as Example 1 except that the O ₂ plasma treatment was not performed.
-Comparative Example 2-
In Example 1, a sample was produced under the same conditions as in Example 1 except that the acid treatment was not performed.
-Comparative Example 3-
In Example 1, a sample was produced under the same conditions as in Example 1 except that it was treated in pure water at 80 ° C. for 24 hours instead of acid treatment.
-Comparative Example 4-
In Example 8, a sample was produced under the same conditions as in Example 8 except that the acid treatment was not performed.
-Comparative Example 5-
In Example 12, a sample was produced under the same conditions as Example 12 except that the acid treatment was not performed.

The production conditions of the above examples and comparative examples are summarized in Table 1.

[Confirmation of titanium oxide layer formation]
When the composition of the surface of the sample of the example and the comparative example was examined by energy dispersive X-ray analysis (EDX), as shown in Table 2, after the plasma treatment was performed on the PEEK substrate in an oxygen atmosphere, the sol-gel coating treatment was performed. In the sample obtained in this way (Comparative Example 2), it was confirmed that a titanium oxide gel layer was formed on the surface of the PEEK substrate because 1.4 atomic% Ti was detected on the surface. Furthermore, when the same sample was immersed in 0.1 M hydrochloric acid at 80 ° C. for 24 hours (Example 1), 0.5 atomic% Ti was detected on the surface, so that the titanium oxide gel layer on the surface of the PEEK substrate was It was confirmed that it was dissolved somewhat by treatment with hydrochloric acid but remained after treatment with hydrochloric acid.

  In the sample obtained by projecting the titanium oxide particles onto the PEEK base material (Comparative Example 4), 16.0 atomic% Ti was detected on the surface, so the titanium oxide particles on the surface of the PEEK base material. Was confirmed to be embedded. When the sample was immersed in 2M hydrochloric acid at 80 ° C. for 24 hours (Example 5), it was confirmed that the amount of Ti on the surface did not change and titanium oxide particles remained.

  In the sample obtained by projecting the titanium oxide particles to the PEEK base material and then performing the sol-gel coating treatment (Comparative Example 5), 16.6 atomic% of Ti was detected on the surface, so PEEK It was confirmed that titanium oxide particles were embedded in the surface of the base material, and a titanium oxide gel layer was formed thereon. Further, when the sample was immersed in 0.1 M hydrochloric acid at 80 ° C. for 24 hours (Example 12), 15.3 atomic% Ti was detected on the surface, so that the titanium oxide gel layer was somewhat dissolved by the hydrochloric acid treatment. However, it was confirmed that it remained after the treatment with hydrochloric acid.

[Formation of functional groups on PEEK substrate]
When the X-ray photoelectron spectra before and after plasma treatment or UV treatment were examined for the PEEK substrate, as shown in FIG. 1 and Table 3, on the untreated PEEK substrate (Comparative Example 1), C—C, C— Only peaks derived from O, C = O and π-π bonds were detected.
On the other hand, when the PEEK substrate was subjected to plasma treatment (Examples 1, 3, 4, 5, 6, 7, Comparative Examples 2 and 3) or UV treatment (Example 2) in an oxygen atmosphere, the surface thereof was obtained. , A new peak derived from O—C═O was observed, and the peak intensity derived from C═O also increased. From this, it was confirmed that O—C═O and C═O bonds were formed on the PEEK substrate by plasma treatment or UV treatment.

[Adhesion of titanium oxide layer]
For a sample in which a titanium oxide surface layer is formed on a PEEK base material, the surface layer on the base material is analyzed by EDX after the adhesive tape is once applied to the surface layer and then peeled off. Was evaluated (hereinafter referred to as “tape test”). The evaluation results are shown in Table 4. In the table, “◯” indicates that no peeling of the surface layer was observed, and “X” indicates that peeling was observed.

As shown in Table 4, in the sample (for example, Example 1) obtained through O ₂ plasma treatment, sol-gel coating treatment, and acid treatment, the Ti amount on the sample surface did not change before and after the tape test. The titanium oxide layer was not peeled off. Similarly, no peeling was observed in the sample (Example 2) obtained by performing UV treatment instead of plasma treatment.
On the other hand, in the sample (Comparative Example 1) obtained by performing the sol-gel coating treatment and the acid treatment without performing the plasma treatment or the UV treatment, the amount of Ti was significantly reduced after the tape test as compared with before the tape test. It can be seen that the surface layer of was peeled off with the tape.

  Moreover, in the sample (for example, Example 8) obtained through the projection treatment and the acid treatment, the Ti amount on the sample surface did not change before and after the tape test, and thus no peeling of the surface layer was observed. Furthermore, even in the sample (Example 12) obtained through the projection treatment, sol-gel coating treatment and acid treatment, the amount of Ti on the sample surface did not change before and after the tape test. There wasn't.

[Zeta potential of titanium oxide layer]
When the zeta potential of the surface layer in the 10 mM sodium chloride (NaCl) aqueous solution was examined for the samples of Examples 1, 8, and 12 and Comparative Examples 2, 4, and 5, formation of the surface layer as shown in Table 5 was performed. Regardless of whether the means was O ₂ plasma treatment and sol-gel coating treatment or projection treatment, all samples not subjected to acid treatment thereafter showed a negative zeta potential.
On the other hand, all the samples subjected to the acid treatment after the surface layer forming step showed a positive zeta potential.

[Apatite forming ability of titanium oxide layer]
A titanium oxide layer formed on a PEEK base material is immersed in a simulated body fluid (SBF), and after 3 days, the presence or absence of apatite formation on the surface is determined by thin film X-ray diffraction, and the amount of apatite formed is determined by a scanning electron microscope. When examined by observation, in the samples whose surface layer was positively charged, as shown in Table 4, apatite was deposited on the entire surface within 3 days of SBF immersion.
On the other hand, in the sample whose surface layer was negatively charged, apatite did not precipitate even after 3 days of SBF immersion.
In Table 4, the coverage indicates the ratio of the area where the apatite is deposited with respect to the area of the sample surface, where “−” is less than 10% and “+” is 10% or more and 50%. %, “++” represents 50% or more and less than 90%, and “++” represents 90% or more.

Claims (18)

A substrate made of polyetheretherketone (PEEK);
A surface layer made of titanium oxide and fixed to a predetermined portion of the surface of the substrate;
A bone repair material, wherein the surface layer has a positive zeta potential in a neutral aqueous solution.   The bone repair material according to claim 1, wherein the positive zeta potential is +3 mV or more and +20 mV or less.   The bone repair material according to claim 1 or 2, wherein the surface layer is fixed to the predetermined site by chemically bonding the titanium oxide and the polyetheretherketone.   The bone repair material according to claim 3, wherein the titanium oxide is in a gel form, the polyether ether ketone has a hydrophilic group at a molecular end thereof, and the chemical bond is interposed through the hydrophilic group.   The bone repair material according to claim 4, wherein the surface layer has a thickness of 0.5 μm to 10 μm.   The bone repair material according to claim 4 or 5, wherein the hydrophilic group is an oxycarbonyl (-O-C = O) group or a carbonyl (-C = O) group.   2. The surface layer is fixed to the predetermined portion by the titanium oxide having a particulate shape, and the particles are partially biting into the base material in a state of being exposed from the surface of the base material. Or the bone repair material of 2.   The bone repair material according to claim 7, wherein the titanium oxide has an average particle diameter of 1 μm or more and 1 mm or less.   The surface layer has a laminated structure of an inner layer made of particulate titanium oxide and an outer layer made of gel-like titanium oxide that uniformly covers the inner layer, and part of the titanium oxide particles constituting the inner layer are the base material The bone repair material according to claim 1 or 2, wherein the surface layer is fixed to the predetermined portion by biting into the base material while being exposed from the surface of the base material.   The bone repair material according to claim 9, wherein the titanium oxide constituting the inner layer has an average particle diameter of 1 μm or more and 1 mm or less.   The bone repair material according to claim 9, wherein the titanium oxide constituting the outer layer has a thickness of 0.5 μm to 10 μm. A surface layer forming step of preparing a base material made of polyether ether ketone and forming a surface layer made of titanium oxide at a predetermined portion of the base material surface;
A method for producing a bone repair material, comprising sequentially performing an acid treatment step in which an acid is brought into contact with the surface layer.   The manufacturing method according to claim 12, wherein the acid is one or more aqueous solutions selected from hydrochloric acid, nitric acid, and sulfuric acid, and has a concentration of 0.01M or more and 5M. The surface layer forming step includes
Forming a hydrophilic group at the predetermined site;
14. The method according to claim 12, further comprising a step of bringing the sol of titanium oxide into contact with the same portion and gelling the sol.   The production method according to claim 14, wherein the hydrophilic group is an oxycarbonyl (—O—C═O) group or a carbonyl (—C═O) group.   The manufacturing method according to claim 14, wherein the step of forming the hydrophilic group is plasma treatment or ultraviolet irradiation in an oxygen atmosphere. The surface layer forming step includes
The manufacturing method according to claim 12 or 13, which is a projecting step of projecting titanium oxide particles onto the predetermined part. The surface layer forming step includes
Projecting titanium oxide particles onto the predetermined site;
14. The method according to claim 12, further comprising a step of bringing a titanium oxide sol into contact with the same portion and / or the projected titanium oxide particles and gelling the sol.

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