阅读说明：本技术 抗菌性生物植入物的制造方法 (The manufacturing method of antibiotic property bioimplant ) 是由 土屋弘行 桥本幸信 于 2017-03-31 设计创作，主要内容包括：本发明提供一种能长期稳定地发挥优异的抗菌性的抗菌性生物植入物。抗菌性生物植入物的制造方法,对基材(2)依次进行阳极氧化处理、酸处理及碘处理,由此得到抗菌性生物植入物(1)。(The present invention provides a kind of antibiotic property bioimplant that can play excellent antibiotic property steadily in the long term.The manufacturing method of antibiotic property bioimplant successively carries out anodized, acid processing to substrate (2) and iodinates, thus obtains antibiotic property bioimplant (1).)

1. a kind of manufacturing method of antibiotic property bioimplant, which is characterized in that

Anodized, acid processing are successively carried out to the substrate being made of metal material and are iodinated,

Thus following antibiotic property bioimplant: the anodic scale for having the substrate and being laminated on the substrate is obtained Film and the anodic oxide coating have the rich iodine layer being located at the interface side of the substrate.

2. the manufacturing method of antibiotic property bioimplant according to claim 1, which is characterized in that

The acid processing is sulfuric acid treatment.

3. the manufacturing method of antibiotic property bioimplant according to claim 1, which is characterized in that

The acid processing is that the substrate is impregnated in the processing of acid；The acid includes sulfuric acid and hydrogen peroxide.

4. the manufacturing method of antibiotic property bioimplant according to any one of claim 1 to 3, which is characterized in that

The metal material is titanium or titanium alloy.

5. the manufacturing method of antibiotic property bioimplant according to any one of claim 1 to 4, which is characterized in that

Carrying out washing treatment is also carried out after described iodinate.

Technical field

The present invention relates to the manufacturing methods of the bioimplant with antibiotic property.

Background technique

Bioimplant is repaired or is substituted to the function of human body reduced or losed by wound or disease etc., is made Increased together with the increase of advanced age population with number.Such bioimplant requires that biology can be substituted steadily in the long term after surgery Function.In recent years scientific and technical development is also very significant in terms of bioimplant, leaves certain achievement at present.

However, the problem of bioimplant remains first is that postoperative infection disease.It is set using joint prosthesis as representative in implantation material Change it is postoperative, in the worst case will be by again if bacterium is around implantation material or infectious disease is bred and caused to operative site After operation pulls out the joint prosthesis of infection and carries out the treatment of infection using antibiotic, joint prosthesis is replaced again.Also, prognosis is not Arthrodesis or limbs amputation etc. are had in the case where good is difficult to the problem of restoring.

For such problems, the research to bioimplant endowing antibacterial has energetically been carried out in recent years.As right The method of bioimplant endowing antibacterial, it is known to using as the method for the iodine of antimicrobial component.For example, patent document 1,2 In by anodic oxidation or chemicals processing oxidation etc. form micropore or bumps, be impregnated in iodine or iodine compound by electrophoresis Micropore or bumps obtain antibiotic property by washing out iodine.It is expected that such iodine bring anti-microbial property plays steadily in the long term Effect.

Summary of the invention

Problems to be solved by the invention:

The subject of the invention is to provide a kind of antibiotic property bioimplants that can play excellent antibiotic property steadily in the long term.

The means solved the problems, such as:

The inventors of the present invention carefully study repeatedly to solve the above-mentioned problems after, has found and constitute following solution, thus complete At the present invention；

(1) a kind of manufacturing method of antibiotic property bioimplant, successively carries out anodic oxidation to the substrate being made of metal material Processing, acid are handled and are iodinated, and thus obtain antibiotic property bioimplant, the antibiotic property bioimplant has the substrate And the anodic oxide coating and the anodic oxide coating being laminated on the substrate have the interface side being located at the substrate Rich iodine layer；

(2) manufacturing method of antibiotic property bioimplant described in above-mentioned (1), the acid processing is sulfuric acid treatment；

(3) manufacturing method of antibiotic property bioimplant described in above-mentioned (1), the acid processing is that the substrate is impregnated in acid Processing；The acid includes sulfuric acid and hydrogen peroxide；

(4) manufacturing method of antibiotic property bioimplant described in any one in above-mentioned (1)~(3), the metal material are titanium Or titanium alloy；

(5) manufacturing method of antibiotic property bioimplant described in any one in above-mentioned (1)~(4), after described iodinate Also carry out carrying out washing treatment.

Invention effect:

According to the present invention, it can obtain playing the antibiotic property bioimplant of excellent antibiotic property steadily in the long term.

Detailed description of the invention

Fig. 1 is the partial enlargement outline section explanation for showing the antibiotic property bioimplant of an implementation form according to the present invention Figure；

Fig. 2 is the flow chart for showing the manufacturing method of antibiotic property bioimplant of an implementation form according to the present invention；

Fig. 3 is the figure for showing the section observation result in embodiment 2, and (a) is field emission scanning electron microscope photo, is (b) The elemental scan (mapping) of iodine.In addition, Fig. 1 schematically shows Fig. 3；

Fig. 4 is the figure for showing the section observation result in comparative example 1, and (a) is field emission scanning electron microscope photo, is (b) The elemental scan of iodine；

Fig. 5 be show iodine in embodiment 2 through when wash out test result chart.

Specific embodiment

< antibiotic property bioimplant >

Hereinafter, the antibiotic property bioimplant of an implementation form according to the present invention is described in detail referring to Fig.1 (hereinafter sometimes referred to " bioimplant ").

The bioimplant 1 of shown in FIG. 1 implementation form has by iodine bring antibiotic property, has substrate 2 and anode Oxide scale film 3.

(substrate)

Substrate 2 is made of metal material.As metal material, it can be mentioned, for example titanium, cobalt, titanium alloy, cobalt alloy, cochromes, no Become rusty steel etc., but as long as can serve as bioimplant with regard to without being limited thereto.

In the metal material of illustration, since bone affinity is high, excellent with the bond strength of bone and bioaffinity is also high, Therefore preferably titanium or titanium alloy.In other words, the preferred titanium of the metal material of implementation form or titanium alloy.As titanium preferably such as ASTM Grade1~4 recorded in F67.As titanium alloy, it can be mentioned, for example Ti-6Al-4V ELI alloys (ASTM F136), Ti-6Al- 7Nb(ASTM F1295), Ti6Al-2Nb-1Ta-0.8Mo(JIS T 7401-3), Ti-15Mo-5Zr-3Al(ISO 5832- 14) etc..The titanium alloy being made of Ti-6Al-4V ELI alloy (ASTM F136) in the titanium or titanium alloy more preferably illustrated.

(anodic oxide coating)

Anodic oxide coating 3 is the epithelium being laminated on above-mentioned substrate 2, is formed via aftermentioned anodized.Therefore, The anodic oxide coating 3 of this implementation form has the micropore 33 and micro concavo-convex 34 formed by anodized.Micropore 33 be the hole of equivalent circle diameter is 0.1~5 μm under area conversion round or multilateral shape.Micro concavo-convex 34 is by fine The bumps that hole 33 deforms or micropore 33,33 adjacent each other is bonded to each other and is formed, measure according to JIS B0601-2001 Arithmetic mean roughness (Ra) is 0.2 μm or more.Iodine or iodine compound is set to be impregnated in such micropore 33 and micro concavo-convex 34 In can obtain antibiotic property.

The anodic oxide coating 3 of this implementation form has rich iodine layer 31.Rich iodine layer 31 is content of iodine in anodic oxide coating 3 The position of most stratiforms.Content of iodine refers to the amount for constituting the iodine of iodine or iodine compound.In this implementation form, rich iodine layer 31 In anodic oxide coating 3 with the interface side S of substrate 2.The iodine or iodine compound being impregnated in micropore 33 and micro concavo-convex 34 It is relatively easy to wash out, can more early be reduced by these iodine or iodine compound bring antibiotic property, and according to this structure, it can inhibit easily Ground washes out iodine or iodine compound from rich iodine layer 31, so that the slow release of iodine is persistently played, even if being washed after iodinating Processing can also obtain the antibiotic property excellent by iodine bring steadily in the long term.

There is the confirmation of rich iodine layer 31 can carry out for example, by following manner anodic oxide coating 3: carrying out section After polishing (hereinafter sometimes referred to " CP ") processing, seen using field emission scanning electron microscope (hereinafter sometimes referred to " FE-SEM ") Section is examined, the elemental scan carried out by energy dispersion-type X-ray analytical equipment (hereinafter sometimes referred to " EDS ") is executed.

In this implementation form, rich iodine layer 31 is located at the closest interface side S with substrate 2 in anodic oxide coating 3.Change speech It, rich iodine layer 31 is located at the position 32 other than the rich iodine layer 31 in anodic oxide coating 3 and between substrate 2.Therefore, this implementation shape Rich iodine layer 31 is contacted with substrate 2 in state.According to this structure, iodine can be inhibited to be washed out easily.In addition, rich iodine layer 31 and base The contact of material 2 means that rich iodine layer 31 is substantially contacted with substrate 2.That is, rich iodine layer 31 contacted with substrate 2 be further include following situation Concept: the major part in rich iodine layer 31 is contacted with substrate 2, and remaining a small amount of part separates with substrate 2 and is located at and substrate 2 Near the S of interface.

The rich iodine layer 31 of this implementation form is made of the inorganic compound at least containing iodine, more specifically, by least containing There is the inorganic compound of iodine and the element from substrate 2 composition.According to this structure, can inhibit to wash out iodine easily.This reality The rich iodine layer 31 for applying form includes also containing the element from substrate 2 and from the inorganic of the aftermentioned element for iodinating bath Compound.

Again, it is preferable that the rich iodine layer 31 of this implementation form contains the inorganic compound containing iodine and the organic compound containing iodine. Whereby, the slow release of iodine or iodine compound is more excellent.

The anodic oxide coating 3 of this implementation form is free of iodine in the position 32 other than rich iodine layer 31.It whereby, can be for a long time It steadily releases iodine or iodine compound, slow release is excellent.Mean after carrying out CP processing without iodine, is observed using FE-SEM disconnected Face, when executing EDS elemental scan, iodine will not be measured as being more than measurement error standard and the concentration that can not keep away contamination levels.And Be not excluded for as shown in the position 32 of (b) in Fig. 3 because measurement error, impurity can not be kept away etc. due tos detect iodine the case where.This The position 32 of implementation form is by the inorganic compound group containing the element from substrate 2 and the element from anodized bath At.

Preferably 3~10 μm of the thickness of anodic oxide coating 3.Upper limit value can be 6 μm or less or 5 μm or less.If 3 μm with On, then it can make fully containing iodine or iodine compound in rich iodine layer 31 and micropore 33 and micro concavo-convex 34, so as to longer Phase plays consistently excellent antibiotic property.If the dhering strength of anodic oxide coating can reduce sometimes more than 10 μm.

Also, preferably 0.1~2 μm of thickness of rich iodine layer 31.It can make rich iodine layer 31 fully containing iodine or iodine compound, thus Energy longer-term plays consistently excellent antibiotic property.

Anodic oxide coating 3 and the respective thickness of rich iodine layer 31 can be seen by after carrying out CP processing using FE-SEM Section is examined to measure.Measurement position is at five, and taking its average value is anodic oxide coating 3 and the respective thickness of rich iodine layer 31.Separately Outside, when measuring the thickness of rich iodine layer 31, also execution EDS elemental scan is to especially determine rich iodine layer 31.

Anodic oxide coating 3 is to the dhering strength of substrate 2 preferably in 22MPa or more.Whereby, it can make and the combination of bone is strong Spend excellent, and the dhering strength (static stretch intensity) of epithelium and substrate needed for capable of coping with medical part is in 22MPa or more This requirement.As the upper limit value of dhering strength, about 70MPa etc. can be enumerated, but the intensity of binder can be depended on.It is closely sealed Intensity is the value measured according to ASTM F1147.

The upper limit of the content of iodine of bioimplant 1 can be 100 μ g/cm²Below, 50 μ g/cm²Below, 25 μ g/cm²With Under, 20 μ g/cm²Below or 16 μ g/cm²Hereinafter, lower limit can be 4 μ g/cm²Above or 8 μ g/cm²More than.Whereby, long-term to play Antibiotic property also still ensures that sufficient iodine number.

Also, the content of iodine of bioimplant 1 can be 4~20 μ g/cm², 4~16 μ g/cm², preferably 10~16 μ g/ cm².According to this structure, above-mentioned anodic oxide coating 3 can be maintained to the dhering strength of substrate 2 and long-term performance antibiotic property Still ensure that sufficient iodine number.Content of iodine is the value measured by energy dispersion-type X-ray analytical equipment.The content of iodine of this implementation form It is the value after being iodinated and carrying out carrying out washing treatment.

As the form of above-mentioned bioimplant 1, it can be mentioned, for example joint prosthesises, artificial bone-head, artificial dental root, inside and outside solid Determine material, external fixator etc., but not limited thereto.

The manufacturing method > of < antibiotic property bioimplant then, in case where manufacturing above-mentioned bioimplant 1, joins The manufacturing method of the antibiotic property bioimplant of an implementation form according to the present invention is described in detail according to Fig. 2.

As shown in Fig. 2, anodized, the process S2 of process S1 is successively carried out in this implementation form to above-mentioned substrate 2 Acid processing and process S4 iodinate, thus obtain bioimplant 1.Also, in this implementation form, at the iodine of process S4 The second carrying out washing treatment of process S5 is also carried out after reason.Also, in this implementation form, also carry out process S3 the first carrying out washing treatment and The drying process of process S6.Alternatively, it is also possible to be before the anodized of process S1 carry out process S0 ungrease treatment.With Under, this implementation form is described in detail by the sequence of process S0~S6.

(process S0；Ungrease treatment)

Ungrease treatment is the processing of the impurity such as the spot for removing 2 surface of substrate.For example, ultrasonic washing, dipping washing can be used Deng, in addition, cleaning solution can enumerate the aqueous solution etc. containing sodium hydroxide and surfactant.Furthermore in order to wash away the cleaning solution of attachment, Water displacement wash is carried out with pure water.

(process S1: anodized) anodized is that substrate 2 is impregnated in electrolyte, is anode with substrate 2 The processing being electrolysed.By the processing, the anodic oxide coating for not having rich iodine layer 31 can be formed on substrate 2.

As electrolyte, it can be mentioned, for example sulfuric acid-water mixing baths, sulfuric-phosphoric-water mixing bath, sulfuric-phosphoric-peroxide Change the acidic electrolysis baths containing sulfuric acid such as hydrogen-water mixing bath, sulfuric-phosphoric-ascorbic acid-water mixing bath.Each mixing illustrated In bath, the concentration of each constituent such as sulfuric acid can be suitably set.For example, can make in sulfuric-phosphoric-hydrogen peroxide-water mixing bath The concentration of sulfuric acid is 30~40g/l, the concentration of phosphoric acid is 20~30g/l, the concentration of hydrogen peroxide is 5~15g/l etc..

In addition, can also be instead of above-mentioned acidic electrolysis bath, alkaline electrolyte etc. is used.It, can as alkaline electrolyte Enumerate potassium hydroxide-potassium fluoride-sodium phosphate-aluminium hydroxide-water mixing bath etc..In mixing bath, the concentration example of each constituent The concentration that potassium hydroxide can be such as set as is 165g/l, the concentration of potassium fluoride is 35g/l, the concentration of sodium phosphate is 35g/l, hydroxide The concentration of aluminium is 35g/l etc..

Preferably, acidic electrolysis bath is used when substrate is titanium, titanium alloy or stainless steel, and alkali is used when substrate is cochrome Property electrolyte.

The range that preferably 23~40 DEG C of the temperature of electrolyte, it is more preferred to 23~35 DEG C of range.As described later, main Flashing discharges in electrolysis, by the thermally-induced heat release of joule.Excessive heat release will lead to falling off for oxide scale film, thus preferably with Electrolyte is cooled down in reaction, does not make the forms such as voltage surge that the temperature of electrolyte is maintained above range.

Electric current for electrolysis is Rectified alternating current.The frequency of Rectified alternating current is preferably in 50Hz or more.This is because with The case where additional direct current carries out anodized significantly improves compared to antibiotic property.Also, the lower limit value of frequency by 50Hz or more, 200Hz or more, 800Hz or more, the sequence of 1000Hz or more are further preferred, and upper limit value presses 10000Hz or less, 5000Hz or less Sequence it is further preferred.This is because antibiotic property can be significantly improved.

Electrolysis preferably has preelectrolysis and main electrolysis.As the condition of preelectrolysis, not flashing electric discharge (plasma is used Body electric discharge) maximum voltage voltage below.In preelectrolysis, preferably voltage is made to gradually rise up to assigned voltage from 0Vrms, as Apply the time of the voltage for preelectrolysis, preferably 10 seconds~2 minutes from becoming assigned voltage, more preferable 20 seconds~1 minute, Further preferred 30 seconds~1 minute.

As the voltage for main electrolysis, preferably 100~210Vrms, more preferable 140~210Vrms, further preferably 170~210Vrms.It whereby can flashing electric discharge.Brownout then not flashing electric discharge (plasma discharge) sometimes And micropore 33 and micro concavo-convex 34 can not be formed, overtension then causes falling off for epithelium sometimes.

Also, as the time for applying the voltage for main electrolysis, preferably 3~10 minutes, more preferable 5~10 minutes, into one Step preferably 6~10 minutes.The thickness of the time too short then epithelium is insufficient, too long, causes falling off for epithelium.

For example, as the condition of preelectrolysis, can be enumerated using arteries and veins when enumerating the case where titanium or titanium alloy are used as substrate Dynamic DC voltage is risen to after defined voltage with the voltage of 0~120Vrms and carries out the processing of electrolysis in 10 seconds~2 minutes, and conduct The condition of main electrolysis can be enumerated using pulsating dc voltage, be carried out at electrolysis in 3~10 minutes with the voltage of 120~210Vrms Reason.

(process S2: acid processing)

Acid processing is the processing being immersed in substrate 2 and anodic oxide coating without rich iodine layer 31 in acid.By the processing, The a part for the barrier layer for being in 33 bottom of micropore and contacting with substrate for being formed in substrate surface can be damaged (damage), occur that the electrolysis in aftermentioned iodinate sufficiently, to form rich iodine layer 31, can also content of iodine be made to increase.

Its reason is inferred as follows.For example, being mixed in above-mentioned anodized using sulfuric-phosphoric-hydrogen peroxide-water Bath is used as electrolyte, when using the titanium alloy that is made of ASTM F136 as the metal material of substrate 2, in anodic oxide coating In with the interface S of substrate 2 and its be formed about sulfur-rich layer.Sulfur-rich layer is the layer being made of the inorganic compound at least containing sulphur, It is the position for the stratiform that sulfur content is most in anodic oxide coating.In the combination of above-mentioned electrolyte and metal material, sulfur-rich layer by Containing sulphur and as the element from substrate 2 titanium and formed containing aerobic inorganic compound.It will be with such sulfur-rich layer When anodic oxide coating carries out acid processing with substrate 2 together, a part of sulfur-rich layer or sulfur-rich layer is by acid dissolution.And, thus it is speculated that Rich iodine layer is formed with by aftermentioned iodinate on the position of sulfur-rich layer dissolution, as a result forms rich iodine in the interface side S with substrate 2 Layer 31.In addition, the position in anodic oxide coating other than sulfur-rich layer is by containing in the combination of above-mentioned electrolyte and metal material Titanium, aluminium, oxygen and phosphorus inorganic compound composition.

As the acid in acid processing, it can be mentioned, for example sulfuric acid, hydrochloric acid, nitric acid and oxalic acid etc..One kind can be used in the acid of illustration Or it two or more is used in mixed way.Preferably sulfuric acid in the acid of illustration.In other words, acid processing preferably sulfuric acid processing.It is preferred that these acid with Hydrogen peroxide is used together.For example, pure titanium, titanium-niobium alloy etc. are only unable to fully carry out sour processing with sulfuric acid sometimes, by being used in combination Sulfuric acid and hydrogen peroxide can sufficiently complete sour processing.

Acid is preferably used with the state of aqueous solution.The concentration of aqueous acid medium preferably 5~20 mass %, more preferable 5~15 matter Measure %.

Preferably 40~70 DEG C of the temperature of aqueous acid, more preferable 50~70 DEG C.Liquid temperature is too low, is difficult to form rich iodine layer 31 tendency.Also, liquid Wen Taigao then can probably make anodic oxide coating 3 reduce the dhering strength of substrate 2.

Dip time preferably 1~10 minute, more preferable 1~5 minute.Dip time is too short, is difficult to form rich iodine layer 31 Tendency.Also, dip time is too long, anodic oxide coating 3 can probably reduced to the dhering strength of substrate 2.

It is preferred that suitably changing the condition of acid processing according to the type of the metal material of substrate.For example, following situations can be enumerated: If pure titanium, then the group of aqueous acid is made to become 10 mass % of 10 mass % of sulfuric acid and hydrogen peroxide, dip time is 7 minutes；If For Ti-6Al-4V ELI alloy (ASTM F136), then the group of aqueous acid is made to become 10 mass % of sulfuric acid, dip time is 3 points Clock；In addition, if Ti-6Al-7Nb(ASTM F1295) so that the group of aqueous acid is become 10 mass % of sulfuric acid and hydrogen peroxide 10 Quality %, dip time are 10 minutes.

(the S3: the first carrying out washing treatment of process)

First carrying out washing treatment is after above-mentioned acid processing, to substrate 2 and on the anodic oxide coating without rich iodine layer 31 The processing that the acid of attachment is rinsed.Cleaning solution it can be mentioned, for example pure water etc., but not limited to this.The liquid temperature preferably 20 of cleaning solution~ 30℃.It can be mentioned, for example rinsings to wash for washing methods, dipping washs etc., but not limited to this.

(process S4: iodinating)

Iodinate is that substrate 2 and anodic oxide coating without rich iodine layer 31 are impregnated in the electrolysis containing iodine or iodine compound Liquid, the processing being electrolysed using substrate 2 as anode.By the processing, rich iodine layer 31 can be formed in the interface side S with substrate 2, So as to obtain bioimplant 1.In above-mentioned anodized, used using sulfuric-phosphoric-hydrogen peroxide-water mixing bath As electrolyte, when using the titanium alloy that is made of ASTM F136 as the metal material of substrate 2, rich iodine layer 31 have containing Iodine and as the element from substrate 2 titanium and also containing aerobic inorganic compound, and due in iodinating iodate close The organic compound of the iodine of object.In addition, in the combination of above-mentioned electrolyte and metal material, rich iodine layer 31 in anodic oxide coating 3 Position 32 in addition is made of the inorganic compound containing titanium, aluminium, oxygen and phosphorus.

As the iodine compound in iodinating, it can be mentioned, for example the inorganic compound of iodine, organic compounds of iodine etc..As The inorganic compound of iodine, it can be mentioned, for example silver iodide, potassium iodide, nickel iodide, ferric iodide, stannic iodides etc..As organising for iodine Close object, it can be mentioned, for example chains saturated hydrocarbons such as methyl iodide, iodoethane, iodate propane, iodate butane, iodate isopropyl alkanes and its Derivative；Chains unsaturated hydrocarbons and its derivatives such as ethylene iodide, propene iodide, iodate butylene, iodate propine, iodate phenylacetylene Object；Benzene iodide, iodate benzyl, iodate benzoyl, iodate acetophenone, penylene dimethyl iodine, iodate phenolphthalein, iodate benzenediol, ring paste The aromatic series hydrocarbons and their derivates such as essence-iodine inclusion compound；The heterocyclic compounds such as trimethyl sulfonium iodide, triphenyl phosphonium iodide sulfonium；Polyethylene Heterocycle polymers such as Iodophors (hereinafter sometimes referred to " PVPI), polyvinyl phthalimide iodine etc..The iodine of illustration A kind of or two or more uses of mixing can be used in compound.

Also, the PVPI in the iodine compound illustrated is next from the safety to human body, environmental protection, the angle of bioaffinity It sees more preferably.

Iodine and iodine compound preferably use in the state of aqueous solution.As the concentration of iodine in aqueous solution or iodine compound, It is preferred that 0.1~10.0 mass %, more preferable 0.4~6.0 mass %.

As the temperature of iodine and/or the aqueous solution of iodine compound, preferably 20~40 DEG C, more preferable 23~40 DEG C, further It is preferred that 23~35 DEG C.

Electric current for electrolysis is direct current.It is preferred that constant current density, more preferable current density is in 0.05~10A/dm² Range.

As the voltage for electrolysis, preferably 100~250Vrms, more preferable 100~200Vrms.As electrolysis time, It is preferred that 1~20 minute, more preferable 3~18 minutes.

Electrolysis is preferably carried out with two stages.The voltage that first stage electrolysis is preferably electrolysed with second stage permanent electricity below Pressure carries out.As the voltage of first stage electrolysis, preferably 0~150Vrms.Also, the voltage as second stage electrolysis, preferably 100~250Vrms, more preferable 150~250Vrms, further preferred 180~210Vrm.For example, enumerating titanium or titanium alloy When as the case where substrate, can enumerate in the first stage electrolysis in, with the voltage of 0Vrms to such as 120~150Vrms or so into It after the electrolysis of row certain time, is electrolysed as second stage, also with the voltage further progress electricity of 150Vrms to 250Vrms or so Solution.

The electrolysis time total as first stage electrolysis and second stage electrolysis, preferably 1~20 minute, more preferable 3~ 18 minutes, the electrolysis time of especially extension second stage electrolysis can be such that content of iodine increases.

Adjusting the condition that iodinates illustrated then can be by the control of above-mentioned content of iodine in desired value.Also, it is preferred that according to substrate Metal material type suitably change acid processing condition.Such as can enumerate following situations: if pure titanium, then the first stage is electric Solution carries out 0~150Vrms of voltage 8 minutes, and second stage electrolysis carries out voltage 210Vrms 7 minutes；If Ti- 6Al-4V ELI alloy (ASTM F136), then first stage electrolysis carry out 0~150Vrms of voltage 6 minutes, second stage Electrolysis carries out voltage 180Vrms 7 minutes；In addition, if Ti-6Al-7Nb(ASTM F1295) then the first stage electrolysis make Voltage is that 0~150Vrms is carried out 6 minutes, and second stage electrolysis carries out voltage 210Vrms 7 minutes.

(the S5: the second carrying out washing treatment of process)

Second carrying out washing treatment is the processing being rinsed to the remaining iodine or iodine compound that adhere on bioimplant 1.By The processing can inhibit to adhere to iodine or iodine compound on the encapsulating material for encapsulating bioimplant 1 and encapsulating material is made to change colour, is bad Change, so as to steadily take care of bioimplant 1.Also, bioimplant 1 because anodic oxide coating 3 has rich iodine layer 31, so Sufficient content of iodine is still ensured that after second carrying out washing treatment, the result is that excellent antibiotic property can be played steadily in the long term.

As cleaning solution it can be mentioned, for example pure water etc., but not limited to this.Preferably 40~60 DEG C of the temperature of cleaning solution.Whereby, The remaining iodine or iodine compound adhered on bioimplant 1 can sufficiently be rinsed.Washing methods preferably impregnates washing.Dip time It is preferred that 1~10 minute, more preferable 3~7 minutes.In addition, using pure water be cleaning solution, liquid temperature be illustration temperature the case where Under, the second carrying out washing treatment is the washing of so-called warm water.

(process S6: being dried)

Drying process is the processing that the bioimplant 1 after the second carrying out washing treatment is dried.Drying temperature preferably 20~70 ℃.Drying time preferably 1~15 minute.As long as being not limited to the drying condition illustrated in addition, bioimplant 1 can be dried.