CN102417741A

CN102417741A - Design and preparation of iodine antibacterial hydroxyapatite coating titanium and titanium alloy implants

Info

Publication number: CN102417741A
Application number: CN2011101349745A
Authority: CN
Inventors: 周君琳
Original assignee: Individual
Current assignee: Individual
Priority date: 2011-05-24
Filing date: 2011-05-24
Publication date: 2012-04-18

Abstract

The invention relates to a design, a preparation and an application of iodine antibacterial hydroxyapatite coating metal implants. The metal implants comprise pure titanium or a titanium alloy matrix and an iodine antibacterial hydroxyapatite coating which comprises hydroxyapatite and povidone iodine particles, wherein iodine is used as an antibacterial additive, and the mass percentage of iodine in the composite coating is 1-3%. The matrix which is pretreated is subjected to a vacuum plasma spraying technology to prepare the composite coating. The composite coating which has the bone ingrowth characteristic of prosthese surface hydroxyapatite and has the antibacterial performance of iodine has a good biocompatibility, a good biomechanical performance and an antibacterial performance, can control the infection and the loosening related with the implants of prosthese and the like, and simultaneously avoids the toxic side effect caused by the whole body antibiotic application and possible adverse events of the drug resistance and the like caused by the local antibiotic application. A titanium alloy femoral joint prosthese example of the hydroxyapatite composite coating containing 2wt% of iodine is shown in Fig. 1. The inhibition rate of hydroxyapatite coatings of different iodine contents to escherichia coli, Bacillus pyocyaneus and staphylococcus aureus is shown in Fig. 2.

Description

The design of iodine antibacterial hydroxylapatite coated titanium and titanium alloy implants and preparation

Technical field the present invention relates to a kind of design, preparation and application of iodine antibacterial hydroxylapatite compound coating metal implants, belongs to the medical biotechnology technical field of material.

Background technology

Win 40350 (hydroxyapatite, be called for short HA) is a kind of typical biological active materials, when its implant into body, can not only guide skeletonization, and can with new bone forming synostosis, and do not produce inflammation or IR.Therefore, often be used as artificial bone, joint prosthesis, artificial dental root and filling material of bone etc.Though Win 40350 has good biological activity and consistency, mechanical property still has some deficits, and is difficult to satisfy medical requirement.The corrosion stability of titanium or titanium alloy, biocompatibility, bone fusion property, mechanical property, workability etc. all meet the requirement of biomaterial, and it is low to have solved Win 40350 intensity, defectives such as toughness and poor mechanical property.But titanium alloy itself does not have the characteristic of guiding skeletonization, and therefore, titanium or titanium alloy surface generates Win 40350, make implant have the good mechanical property of metal_based material concurrently and Win 40350 good biological activity becomes the research focus and obtains breakthrough.At present; The titanium and the titanium alloy material that have hydroxyapatite coating layer have been widely used in clinical as internal fixation materials such as joint prosthesis, dental implant, fracture and backbone correcting and fusion etc.; Benefit extensive patients; But the related infection that is caused by implant has simultaneously become the most serious even calamitous complication of its use; Especially reprocesses Shi Gengyi in open fracture, joint and infect, and hydroxyapatite coating layer also is the convenient place of bacterial adhesion that orthopaedics common pathogens such as streptococcus aureus, intestinal bacteria, Pseudomonas aeruginosa are in implants surface adhesion, breeding and form bacterial biofilm; Cause acute and chronic infection, make operative failure even jeopardize patient's life.It is the effective ways that treatment is infected that whole body is used microbiotic; But during the implants infections relating because the destruction of the biomembranous formation of surface bacteria and local blood circulation; Whole body application microbiotic is difficult to reach local required Plasma Concentration, radical cure is infected, and long-term a large amount of whole bodies application microbiotic can produce serious toxic side effect and superinfection etc. to important organs such as liver kidney brains.Think that at present biomaterial is carried out surface treatment, and to make it to have concurrently the effect that control infects be the Perfected process of avoiding this type of complication.Recently; There is the research report that microbiotic is introduced the bioactive coating that the hydroxyapatite coating layer preparation has anti-microbial property; But the topical application microbiotic is prone to make body to produce bacterial drug resistance, thus should use cautiously, and remain in problem in many-sides such as microbiotic controlled release and carrier stability thereof.Because silver ions has the extensive interest that the high-efficiency antimicrobial effect causes the investigator recently, and has successfully prepared argentiferous hydroxyapatite coating layer, but existing research shows that silver has cytotoxicity to human body, also is restricted its clinical use.So it is clinical urgently required exploring and preparing safe and effective, practical, novel antibacterial hydroxyapatite coating layer biomaterial, has important clinical application value.

Antibiotic, the germicidal action of iodine are known together already.Iodine is through the cytoplasmic reactive group of oxidizing bacteria, combines to make it sex change with proteinic amino and brings into play sterilization functions.Iodophor is the organic double compound of iodine and Povidone, USP/EP; Bring into play persistent disinfection through the slow release free-iodine; Both can be used for skin and also can be used for mucous membrane and wound, even can be used for body cavity (thoracic cavity, abdominal cavity, joint cavity) sterilization, have antimicrobial spectrum widely; Not only to common bacteria, and to fungi, tubercule bacillus and virus etc. good killing action is arranged all.And iodine is the necessary element of body, thyroxinic important component, and must have a certain amount of absorption every day.If iodine is combined in implant and hydroxyapatite coating layer use, the means of control implant of can yet be regarded as efficient, safe and operation infections relating thereof.

Research shows that the method for preparing coatings such as Win 40350 comprises plasma spraying, magnetic cosputtering method, bionic method, electrochemical deposition method and sol-gel method etc.But at present unique be suitable for that industrialization produces hydroxyapatite coating layer plasma spraying technology only arranged, the coating physicochemical property that additive method is made is relatively poor relatively, and production process is complicated, has increased production cost and production cycle, has limited clinical study and use.

The present invention adopts the vacuum plasma spray technology, is the hydroxyapatite coating layer material that the matrix preparation contains the iodine antiseptic-germicide with titanium and titanium alloy, and prepared material has good biology performance, mechanical property and anti-microbial property.

Summary of the invention:

Based on advantages such as efficient, the safety of good biological activity of Win 40350 and iodine, broad-spectrum antimicrobials; The present invention is a matrix with titanium and titanium alloy; Adopt the siccative blending means to prepare the mixed powder of Win 40350 and PVP-1; Utilize the vacuum plasma spray technology, mixing material is deposited on the matrix, thereby prepares hydroxyapatite bioactive coating with anti-microbial effect.

The concrete technological process of the present invention is following: taking by weighing hydroxyapatite powder and the particle diameter that particle diameter is 85-125um by a certain percentage is 80-150um PVP-1 powder, processes the mixed powder that iodine content is 1-3wt% after mixing.Adopt vacuum plasma spray coating technology, according to following parameter (table 1) with mixed powder be deposited on clean and the titanium alloy substrate of sandblast (like articular prosthesis etc.) on.

Prepared Win 40350-PVP-1 compound coating is yellow-green colour (Fig. 1 contains the titanium alloy femoral stem articular prosthesis of the carboxy apatite composite coating of iodine 2wt%), and coat-thickness is 35-150um.Have good biological activity and anti-microbial property.The in-vitro antibacterial experiment shows that the antibiotic rate of compound coating increases with the increase of iodine content, and streptococcus aureus, intestinal bacteria and Pseudomonas aeruginosa are had obvious anti-microbial effect (Fig. 2).The carboxy apatite composite coating that contains iodine 1-3wt% does not have obvious cytotoxicity.The mtt assay cytotoxicity detects and shows that the compound coating toxicity of 3% iodine content is 0 grade.Acute hemolytic experiment shows that 3% iodine content compound coating hemolysis rate is 0.11%.Can be used for orthopaedics titanium and the surface treatment of titanium alloy metal implant material and improve its bone integration and anti-microbial property.

Table 1 spray parameters scope

Slpm: standard liter/min

Description of drawings

Fig. 1 contains the titanium alloy femoral stem articular prosthesis of the carboxy apatite composite coating of iodine 2wt%

The hydroxyapatite coating layer of the different iodine content of Fig. 2 is to the inhibiting rate of intestinal bacteria, Pseudomonas aeruginosa and streptococcus aureus

Embodiment

1. the surface preparation of titanium and titanium alloy substrate implants: clean and sandblast pretreatment.

2. the preparation of Win 40350 and PVP-1 powder mix takes by weighing hydroxylapatite powder and PVP-1 powder by a certain percentage, and ball milling is done and mixed the mixed powder of processing amount of iodine 1-3wt% in 2 hours.

3. adopt vacuum plasma spray technology, mixed powder is deposited on titanium and the titanium alloy metallic matrix according to following parameter (table 1).

Table 1 spray parameters

Slpm: standard liter/min

Claims

1. one kind is the iodine anti-bacterial carboxy apatite composite coating of matrix with titanium and titanium alloy (Ti-6Al-4V), it is characterized in that said compound coating is made up of Win 40350 and PVP-1; Iodine is as antibiotic added ingredients, and its mass percent in compound coating is 1-3%.

2. by the said coating of claim 1, the particle diameter that it is characterized in that said hydroxyapatite powder is 85-125um, and the PVP-1 particle diameter is 80-150um.

3. by the said iodine anti-bacterial carboxy apatite composite coating of claim 1, it is characterized in that coat-thickness is 35-150um, hole is 100-400um.

4. preparation is characterized in that like the method for each described iodine anti-bacterial carboxy apatite composite coating of claim 1-3 preparation process is:

(1) surface preparation of titanium and titanium alloy metallic matrix: clean and sandblast pretreatment.

(2) Win 40350 and PVP-1 are mixed and made into the mixed powder that amount of iodine is 1-3wt%.

(3) adopt vacuum plasma spray technology, mixed powder is deposited on titanium and the titanium alloy metallic matrix according to following parameter.Plasma gas Ar flow is 40-45slpm, plasma gas H ₂Flow is 8-16slpm, and powder carrier gas Ar flow is 2.0slpm, and spray distance is 200-300mm, and powder feeding rate is 10-30g/min, and vacuum tightness is 100-300mbar, and electric current is 500-650A.

5. by the application of the described iodine anti-bacterial carboxy apatite composite coating of claim 1-3, it is characterized in that compound coating has good antimicrobial property, to the antibiotic rate of intestinal bacteria, Pseudomonas aeruginosa and streptococcus aureus greater than 95%.

6. by the application of the described iodine anti-bacterial carboxy apatite composite coating of claim 5, it is characterized in that compound coating has good bone conduction performance and biocompatibility, no cytotoxicity.