JP3427908B2 - Surface-modified medical material and method for producing the same - Google Patents

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a novel surface-modified medical material, more specifically, a. It replaces the defect site of hard tissue such as bone or tooth caused by pathological or surgical cause, prostheses the function of the defect and induces the generation of new hard tissue around the surface-modified medical material, or It has biocompatibility such as binding to tissue, Suppresses pathological calcification ,
C. Exhibit antibacterial properties, clinical applications useful surface modifying the metallic material of the medical, such as an inorganic material, or relates <br/> a polymer material.

[0002]

2. Description of the Related Art Medical materials are roughly classified into medical metal materials, medical inorganic materials, and medical polymer materials. These medical materials have different properties and therefore
It is appropriately used depending on its purpose and use.

Stainless steel metal represented by SUS316L and COP-1, C represented by HS21 and HS25
One of the major characteristics of medical metal materials represented by o-Cr alloys, stellite, titanium, titanium alloys, etc. is good mechanical properties. Metallic materials for medical use are the first choice for areas such as hip joints and artificial tooth roots where large forces are applied.

[0004] Apatite, one of the major features of the medical inorganic material typified tricalcium phosphate, alumina and zirconia porosity is biocompatible. Apatite, which is one of the inorganic materials for medical use, is a main component of living hard tissues such as bones and teeth, and is known to have extremely excellent properties such as being strongly bonded directly to bones. No big force is applied,
When biocompatibility is emphasized, medical inorganic materials are the first choice.

Teflon, polyethylene, polysulfone,
One of the major characteristics of medical polymer materials represented by polysiloxane, polyester, polyamide and the like is flexibility. Flexible medical polymer materials are the first choice for artificial blood vessels and trachea.

However, these medical metal materials,
The medical inorganic material and the medical polymer material are not ideal materials, and have their respective drawbacks. Biocompatibility is one of the major problems for medical metal materials and medical polymer materials, and mechanical properties, especially brittleness, that is, the feature of being easily cracked and fragile, is a major problem for medical inorganic materials. Is one.

Utilizing the excellent characteristics of these medical materials,
Various conjugations have been investigated to improve problematic properties. Among these, properties such as biocompatibility are determined only by the surface properties of the medical material, and thus surface modification is a very effective method for improving biocompatibility of the material.

For example, in order to combine the excellent mechanical properties of medical metal materials with the excellent biocompatibility of inorganic medical materials,
A method of coating calcium phosphate on the surface of a metal material by plasma spraying has recently been attracting attention. However, plasma spraying requires expensive equipment, and the desired calcium phosphate coating may not be possible depending on the spraying conditions.

Further, in plasma spraying, the calcium phosphate powder is exposed to high temperature plasma in a part of the process, so that part of the surface of the calcium phosphate powder is decomposed into tetracalcium phosphate or calcium oxide. The decomposition product tetracalcium phosphate or calcium oxide is easily dissolved in body fluid such as blood, and as a result, the calcium phosphate film produced by plasma spraying has cracks. It is known that cracks in ceramics or glassy materials remarkably impair the mechanical properties of the material, and therefore calcium phosphate-coated medical metal materials produced by plasma spraying are not sufficiently satisfactory in terms of mechanical properties. There wasn't.

[0010]

The medical material alone having sufficient mechanical properties does not exhibit satisfactory biocompatibility. In order to combine sufficient mechanical properties with multiple useful properties such as biocompatibility, a method of modifying the surface of the medical material with a coating such as plasma spraying has been performed, but the device is expensive and sufficiently satisfactory. I couldn't get any good results. The present invention provides a surface-modified medical material in which useful properties such as biocompatibility are added by simply modifying the surface of the material without impairing the excellent mechanical properties of the material itself, and a method for producing the same. It is a thing.

[0011]

[Means for Solving the Problems] In order to solve the problems of the medical materials described in the preceding paragraph, the present researcher conducted various studies on new medical materials, and as a result, calcium compounds, phosphorus compounds, magnesium compounds, fluorine compounds were found. , a silicon compound, at least one powder selected from the group of silver compound
Mechanically presses the surface of the medical material to apply the powder to the medical material.
At least a portion formed by fixed or solid solution Table <br/> surface modified medical timber fee charges the surface, showed excellent surface properties such as biocompatibility, also useful clinical applications exhibit sufficient mechanical properties by that it Mii that such a medical material, the present invention
Was developed.

That is, the manufacturing method of the present invention and the surface modification
Decorative medical materials include calcium compounds, phosphorus compounds,
Medical powder containing at least one powder selected from the group consisting of magnesium compounds, fluorine compounds, silicon compounds and silver compounds.
At least one selected from the group of the surface-modified medical material and the compound, which is mechanically pressure-contacted with the material surface, and the powder is fixed or solid-solved on at least a part of the surface of the medical material. powder is prepared how surface modification medical material, characterized by mechanically pressed against the medical material surface in such blast treatment.

The term "calcium compound" as used in the present invention means that a calcium element is contained in the compound, and includes metallic calcium, calcium oxide, calcium hydride, calcium hydroxide, apatite, tricalcium phosphate, tetracalcium phosphate, Examples include calcium hydrogen phosphate, calcium dihydrogen phosphate, calcium chloride, calcium acetate, calcium carbonate, calcium silicate and the like.

The phosphorus compound referred to in the present invention is a compound containing elemental phosphorus, and includes phosphorus, potassium phosphate, sodium phosphate, sodium dihydrogen phosphate, tricalcium phosphate, tetracalcium phosphate, Examples include calcium hydrogen phosphate and calcium dihydrogen phosphate.

The term "magnesium compound" as used in the present invention means a compound containing a magnesium element, such as metallic magnesium, magnesium oxide, magnesium hydroxide, magnesium dihydrogen phosphate, magnesium carbonate, magnesium chloride, magnesium fluoride, Examples include trimagnesium phosphate and magnesium silicate.

The fluorine compound referred to in the present invention is a compound containing elemental fluorine, and examples thereof include calcium fluoride, potassium fluoride, sodium fluoride, potassium hydrogen fluoride, magnesium fluoride and the like.

The term "silicon compound" as used in the present invention means that the compound contains elemental silicon, such as silicon, silicic acid,
Examples thereof include silicon oxide, silicon dioxide, potassium silicofluoride, sodium silicofluoride, and magnesium silicofluoride.

The term "silver compound" as used in the present invention means a compound containing a silver element, such as metallic silver, silver oxide, silver carbonate,
Examples are silver chloride and silver fluoride.

The blast treatment as referred to in the present invention is a centrifugal projection type of powder of calcium compound, phosphorus compound, magnesium compound, fluorine compound, silicon compound, silver compound , etc.
This is a method in which powder is mechanically pressed against the surface of a medical material by a blast device such as an air projection type or a belt projection type. The air projection type is generally used, but this is a process of spraying powder by using compressed gas from a nozzle. Examples of the air projecting method include a direct air projecting method in which a tank containing the powder is directly pressurized, and an inductive air projecting method in which the powder is sucked using an ejector nozzle and the powder is sprayed.

The buff treatment in the present invention means calcium compound, phosphorus compound, magnesium compound, fluorine compound,
A buff composed of a flexible material such as cotton cloth, sisal, leather or felt as a rotating body is used as a support for powders of silicon compounds, silver compounds , etc. , and acts between a buff rotating at high speed and a medical material. In this method, the powder is mechanically pressed against the surface of the medical material by a mechanical force.

The barrel treatment referred to in the present invention means that a powder such as a calcium compound, a phosphorus compound, a magnesium compound, a fluorine compound, a silicon compound and a silver compound and a medical material are put into a barrel tank, and medical treatment is performed by rotation, vibration and the like. This is a method of causing relative movement between the medical material and the powder to mechanically press-contact the powder with the surface of the medical material.

The term "fixed" as used in the present invention means that the powder obtained by mechanical pressure contact such as blasting, buffing, barreling, etc. is strongly fixed to the material surface. Therefore, in the present invention, the bonding mode between the film obtained by plasma spraying and the material surface is not defined as sticking. Therefore, the surface-treated medical material produced by plasma spraying is not included in the present invention. The bonding mode between the film obtained by applying an aqueous solution or the like and the material surface is adhesion and is not defined as sticking. Therefore, a surface-modified medical material produced by solution coating or the like is not included in the present invention.

However, the film component of the medical material characterized in that the surface produced by plasma spraying or solution coating is covered with a film, is then applied to the surface of the medical material by mechanical pressure welding such as blasting. If was fixed, the surface-modified medical material and a manufacturing method thereof includes the present invention.

The solid solution referred to in the present invention means a state in which all or part of the powder component is contained in the medical material component by mechanical pressure contact such as blasting, buffing, barreling and the like. Solid solution occurs when two or more different substances come into contact with each other. When the powder comes into contact with the medical material by strong mechanical pressure contact such as blasting, part or all of the powder components are diffused on the surface of the medical material by atomic diffusion or the like and solid-dissolved. It should be noted that the definition of solid solution in the present invention does not require that the components are uniformly dissolved.

The present invention comprises the principles described below.

When the medical material is implanted in a living body, its surface comes into contact with body fluid. Even when the medical material comes into contact with hard tissue such as bone and soft tissue such as muscle, it is the surface of the medical material that comes into contact with these tissues, and in most cases, body fluid exists between them. Therefore, in order to improve the biocompatibility of the medical material, surface modification of the medical material may be considered. On the other hand, the mechanical properties of medical materials are determined as the average of the mechanical properties of the entire material,
Surface modification does not make a significant difference in their mechanical properties.

The surface-modified medical material in which the calcium compound and the phosphorus compound are fixed or solid-solved on at least a part of the surface is, for example, improved in hard tissue affinity of the medical material,
Alternatively, it is effective in promoting generation of hard tissue in contact with a medical material. This can be understood from the fact that apatite or the like is coated on the surface of the medical metal material by plasma spraying to improve biocompatibility of the hip joint or the like. Apatite, which is a component of hard tissue such as bone, is calcium phosphate, and it is known that a calcium phosphate compound exhibits a catalytic action in apatite formation. Further, the calcium compound and the phosphorus compound are dissolved in the body fluid from the surface of the surface-modified medical material, and as a result,
It is also suggested to increase the degree of supersaturation of body fluid with respect to apatite and promote the production of apatite.

The surface-modified medical material in which the magnesium compound and the phosphorus compound are fixed or solid-solved on at least a part of the surface is effective, for example, in preventing calcification on the surface of the medical material. One of the reasons for this is that the magnesium compound suppresses the formation of apatite, which is the cause of calcification. It is known that some phosphorus compounds such as pyrophosphate also suppress the formation of apatite, which is a cause of calcification, like magnesium compounds.

The surface-modified medical material in which the fluorine compound is fixed or solid-dissolved on at least a part of the surface is effective, for example, in imparting antibacterial property and imparting low surface tension to the surface of the medical material. This is one of the reasons that the fluorine compound has antibacterial properties and low surface tension.

The surface-modified medical material in which the silicon compound is fixed or solid-dissolved on at least a part of the surface is effective, for example, in imparting an adhesive force to the surface of the medical material. This is because the silicon compound has compounds with various functional groups,
One of the causes is that the silicon compound effectively acts on adhesion. In addition, it was recently reported that silicon compounds are effective in improving the affinity for hard tissue or promoting the formation of hard tissue. Therefore, it is suggested that the surface-modified medical material in which the silicon compound is adhered to at least a part of the surface may be a material having excellent hard tissue affinity or promoting hard tissue generation.

The surface-modified medical material in which the silver compound is fixed or solid-dissolved on at least a part of the surface is exemplified as being capable of imparting antibacterial property to the surface of the medical material. This is one of the reasons that the silver compound has antibacterial properties.

The examples of surface modification with a calcium compound, a phosphorus compound, a magnesium compound, a fluorine compound, a silicon compound, and a silver compound have been described above, but all of them have the properties of the compound imparted to the surface of the medical material. it is conceivable that. A calcium compound, a phosphorus compound, a magnesium compound, a fluorine compound, a silicon compound, and a silver compound are dissolved on the surface of the surface-modified medical material as catalysts or the like, or gradually dissolved from the surface of the surface-modified medical material to exhibit a desired action. .

The method of the present invention can be applied to compounds containing no calcium element, phosphorus element, magnesium element, fluorine element, silicon element and silver element, but calcium element, phosphorus element, magnesium element, fluorine element and silicon element. When the medical material is treated with a compound containing no element or silver element, the surface modification is not useful or its usefulness is small. For example, modifying the surface of a medical material with sodium chloride is not very useful.

The surface-modified medical material of the present invention is manufactured by the manufacturing method described below. Blast processing,
Buffing, barreling and the like are both methods in which powder is mechanically pressed against the surface of the medical material. For simplicity, only the case of blasting will be described below.

The material is shaped into a desired shape by known methods such as cutting, casting, cutting, sewing, and stitching. Then, at least one powder selected from the group consisting of a calcium compound, a phosphorus compound, a magnesium compound, a fluorine compound, a silicon compound and a silver compound is mechanically pressed onto the surface of the medical material by blasting or the like for treatment. Calcium compound with the medical material surface blasting, etc., phosphorus compounds, magnesium compounds, fluorine compounds, silicon compounds, prior to mechanically press the at least one powder <br/> selected from the group of silver compound, or After that, sterilization and sterilization operations may be added as necessary.

For example, in the case where screw-shaped titanium is made to have biocompatibility with apatite, apatite powder is put into a blasting device or the like, and screw-shaped titanium is blasted. There is no limitation on the air pressure used for blasting, but generally, the higher the air pressure, the greater the treatment effect, and therefore a sufficient effect can be obtained by a short treatment time. However, if the air pressure is too high, the shape of the raw material may be deformed, which is not preferable. The treatment time is determined in relation to the air pressure and the desired degree of treatment. Generally, the longer the treatment time is, the greater the treatment effect is, so that a sufficient effect can be obtained. However, if the processing time is too long, the shape of the raw material may be deformed, which is not preferable.

The powder to be blasted may contain at least one powder selected from the group consisting of calcium compounds, phosphorus compounds, magnesium compounds, fluorine compounds, silicon compounds and silver compounds . The above powders may be mixed. When two or more kinds of powders are mixed and used, it is preferable that both are sufficiently mixed in advance. Since most of the blasting devices take in only the powder in the vicinity of the powder inlet, the desired surface modification may not be possible if the powders are not sufficiently mixed.

It is also useful to blast one surface of the medical material with another powder. In this case, at least one powder needs to be at least one powder selected from the group consisting of calcium compound, phosphorus compound, magnesium compound, fluorine compound, silicon compound and silver compound.

It is also effective to pretreat the powder to be blasted. For example, when it is desired to modify the surface of a medical material with an antibiotic agent which is a carbon compound, there are cases where the surface modifying effect is not sufficient with the antibiotic agent which is a carbon compound alone. In such a case, for example, if apatite or the like is permeated into a solution containing an antibiotic, the antibiotic is adsorbed or absorbed on the surface of the apatite. Therefore, the surface of the medical material can be modified with the antibiotic agent by blasting the apatite or the like having the antibiotic agent adsorbed on the surface.

In the blast treatment, at least one powder selected from the group consisting of a calcium compound, a phosphorus compound, a magnesium compound, a fluorine compound, a silicon compound and a silver compound is mechanically applied to the surface of the medical material by using a gas flow. It is not necessary to use air for the blast treatment, as this is one of the methods of pressure contact treatment. There is no problem to use more inert argon gas, nitrogen gas or the like for the purpose of preventing the oxidation of the surface of the medical material.

Calcium compounds, phosphorus compounds, magnesium compounds, fluorine compounds, silicon compounds, silver compounds
When at least one powder selected from the group of materials is mechanically pressed against the medical material surface by blasting, it is effective to apply a solvent or solution to the treated surface or change the environment such as water vapor pressure Is. For example, when the water vapor pressure is increased when blasting a titanium plate with tetracalcium phosphate and calcium hydrogen phosphate powder, some apatite, which is thought to have been formed by the reaction between tetracalcium phosphate and calcium hydrogen phosphate, is also generated. To do.

At least one powder selected from the group consisting of a calcium compound, a phosphorus compound, a magnesium compound, a fluorine compound, a silicon compound and a silver compound is mechanically pressed onto the surface of the medical material by blasting or the like for treatment. If so, the processing temperature is not limited in the present invention. It is generally known that the higher the processing temperature, the higher the element diffusion rate.
There is also a great risk that the processing equipment will be complicated and that the material will be denatured.

The present invention will be described in more detail by way of examples.

The surface properties of the surface-modified medical material were analyzed using a wavelength dispersive X-ray microanalyzer (hereinafter referred to as XMA). In addition, prior to the analysis, the surface-modified medical material after the surface treatment was sufficiently washed by repeating ultrasonic cleaning in acetone of 10 cc per 1 cm 2 of the treated area 10 times. For example, a medical material having a treated area of 2 square centimeters is ultrasonically cleaned in 20 cc of acetone for 1 minute, the acetone is exchanged, and further ultrasonically cleaned in fresh 20 cc of acetone for 1 minute. This ultrasonic cleaning
The operation of acetone exchange was repeated 10 times. Hereinafter, this cleaning operation is called acetone ultrasonic cleaning. When the antibiotic was used as a powder, the antibiotic eluted in distilled water was analyzed by liquid chromatography.

[0045]

Example 1 Apatite powder was mechanically pressed against a metal titanium plate using a sandblasting device. The processing time was 10 seconds per square centimeter. After the ultrasonic treatment of the treated metal titanium plate with acetone, the surface of the metal titanium plate was subjected to XMA analysis, and peaks of calcium and phosphorus were detected in addition to titanium. The molar ratio of calcium to phosphorus was almost the same as that of the apatite powder.

[0046]

Comparative Example 1 Demonstration of usefulness of the present invention and analytical effectiveness
For this purpose, the metal titanium plate was ultrasonically cleaned with acetone, and then the surface of the metal titanium plate was analyzed by XMA. No peaks other than titanium were detected.

[0047]

Example 2 Tricalcium phosphate powder was mechanically pressed against a metal titanium plate using a blasting device. The processing time was 10 seconds per square centimeter. After the ultrasonic treatment of the treated metal titanium plate with acetone, the surface of the metal titanium plate was subjected to XMA analysis, and peaks of calcium and phosphorus were detected in addition to titanium. The molar ratio of calcium to phosphorus was almost the same as the molar ratio of tricalcium phosphate powder.

[0048]

Example 3 Apatite powder was mechanically pressed against a metallic stainless plate using a blasting machine. The processing time is 1
It was set to 10 seconds per square centimeter. After the treated metal stainless steel plate was ultrasonically cleaned with acetone, the surface of the metal stainless steel plate was analyzed by XMA. Calcium and phosphorus peaks were detected in addition to the stainless steel components. The molar ratio of calcium to phosphorus was almost the same as that of the apatite powder.

[0049]

[Example 4] Apatite powder was mechanically pressure-contacted to a metal vitalium plate using a blasting device. The processing time was 10 seconds per square centimeter. After the ultrasonic treatment of the treated metal vitalium plate with acetone, the surface of the metal vitalium plate was subjected to XMA analysis, whereupon peaks of calcium and phosphorus were detected in addition to the components of the vitalium.
The molar ratio of calcium to phosphorus was almost the same as that of the apatite powder.

[0050]

Example 5 Apatite powder was mechanically pressed against a Teflon plate using a blasting device. The processing time was 10 seconds per square centimeter. After the treated Teflon plate is ultrasonically cleaned with acetone, the surface of the Teflon plate is subjected to XM.
In the A analysis, calcium and phosphorus peaks were detected in addition to the Teflon component. The molar ratio of calcium to phosphorus was almost the same as that of the apatite powder.

[0051]

Example 6 Apatite powder was mechanically pressed against a graphite plate using a blasting device. The processing time was 10 seconds per square centimeter. After the treated graphite plate was ultrasonically cleaned with acetone, the surface of the graphite plate was analyzed by XMA. Calcium and phosphorus peaks were detected in addition to the graphite components. The molar ratio of calcium to phosphorus was almost the same as that of the apatite powder.

[0052]

Example 7 Apatite powder was mechanically pressed against a Teflon cloth using a blasting device. The processing time was 10 seconds per square centimeter. After the treated Teflon cloth is ultrasonically cleaned with acetone, the surface of the Teflon plate is XM
In the A analysis, calcium and phosphorus peaks were detected in addition to the Teflon component. The molar ratio of calcium to phosphorus was almost the same as that of the apatite powder.

[0053]

Example 8 Magnesium oxide powder was mechanically pressed against a metal titanium plate using a blasting device. The processing time was 10 seconds per square centimeter. After the treated metallic titanium plate was ultrasonically cleaned with acetone, the surface of the metallic titanium plate was subjected to XMA analysis, whereupon peaks of magnesium other than titanium were detected.

[0054]

Example 9 Calcium fluoride powder was mechanically pressed against a metal titanium plate using a blasting device. The processing time was 10 seconds per square centimeter. After the treated metallic titanium plate was ultrasonically cleaned with acetone, the surface of the metallic titanium plate was subjected to XMA analysis, and peaks of calcium and fluorine were detected in addition to titanium.

[0055]

Example 10 Silicon dioxide powder was mechanically pressed against a metal titanium plate using a blasting device. The processing time is 1
It was set to 10 seconds per square centimeter. After the treated metal titanium plate was ultrasonically cleaned with acetone, the surface of the metal titanium plate was subjected to XMA analysis, and silicon peaks were detected in addition to titanium.

[0056]

Example 11 Silver oxide powder was mechanically pressure-contacted to a metal titanium plate using a blasting device. The processing time was 10 seconds per square centimeter. After the treated metallic titanium plate was ultrasonically cleaned with acetone, the surface of the metallic titanium plate was subjected to XMA analysis, and a peak of a silver element was detected in addition to titanium.

[0057]

Example 12 Apatite powder was pressed against a metallic titanium plate with a cotton ball by hand pressure so as to rub it. The processing time was 10 minutes per square centimeter. After the ultrasonic treatment of the treated metal titanium plate with acetone, the surface of the metal titanium plate was subjected to XMA analysis, and peaks of calcium and phosphorus were detected in addition to titanium. However, the peaks of calcium and phosphorus were smaller than those in Example 1. The molar ratio of calcium to phosphorus was almost the same as that of the apatite powder.

─────────────────────────────────────────────────── ─── Continuation of the front page (56) References JP-A-62-281954 (JP, A) JP-A-2-241461 (JP, A) JP-A-62-204760 (JP, A) JP-A-2- 140171 (JP, A) JP-A-1-238869 (JP, A) Special Table 9-506273 (JP, A) (58) Fields investigated (Int.Cl. ⁷ , DB name) A61L 27/00

Claims (4)

(57) [Claims] 1. A blasting treatment of at least one powder selected from the group consisting of calcium compounds, phosphorus compounds, magnesium compounds, fluorine compounds, silicon compounds and silver compounds .
Material by medical treatment, buffing, or barreling
It is mechanically pressure-bonded to the surface and is at least compatible with the medical material.
Without melting process or electric discharge process based on the heating device
In addition, a method for producing a surface-modified medical material , characterized in that the powder is fixed or solid-solved on at least a part of the surface of the medical material. 2. A powder which is mechanically pressed against the surface of a medical material.
, Apatite, tricalcium phosphate, tetracalcium phosphate
Um, calcium hydrogen phosphate, calcium dihydrogen phosphate
Selected from the group consisting of calcium, calcium carbonate and calcium silicate.
Powder of at least one calcium compound
The manufacture of the surface-modified medical material according to claim 1.
Method. 3. A powder that is mechanically pressed against the surface of a medical material.
However, as magnesium compounds, metal magnesium, acid
Magnesium fluoride, magnesium hydroxide, dihydrogen phosphate
Gnesium, magnesium carbonate, magnesium chloride, fluorine
Magnesium fluoride, trimagnesium phosphate, silicate mag
Calcium fluoride as a fluorine compound
Aluminum, potassium fluoride, sodium fluoride, hydrogen fluoride
As a compound of silicon and magnesium fluoride
Silicon, silicic acid, silicon oxide, silicon dioxide, silica
Potassium fluoride, sodium silicofluoride, silicofluoride
Gnesium, which is a silver compound, metallic silver, oxide
The silver, silver carbonate, silver chloride or silver fluoride as claimed in claim 1 or 2.
A method for producing the surface-modified medical material described above. 4. Claim 1, claim 2, or claim 3.
It was manufactured by the method for manufacturing surface-modified medical materials listed above.
A characteristic surface-modified medical material.