KR0157034B1 - Method of producing heat generating ceramics body for hyperthermia - Google Patents

Abstract

Provided is a ceramic heating element for thermotherapy having ferromagnetic ferrite particles and a bioactive inorganic layer around the ferrite particles. The inorganic layer has a composition for forming apatite when embedded in the living body, the apatite has a high affinity for the surrounding biological tissue, and has a property that is not recognized as a foreign material by the surrounding tissue by forming an apatite structure The ferrite particles exhibit high efficiency of self-induced heat generation in an alternating magnetic field without generating harmful ions therefrom. The ceramic heating element can be used in various forms of fine powder, shaped body, or fibrous form depending on the means of administration, and can be used for a long time or continuously without adverse effects. Also provided is a method of making the same.

Description

Manufacturing method of ceramic heating element for thermotherapy

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing a ceramic heating element, particularly a ceramic heating element for use in thermotherapy for diseases such as cancer.

In general, cancer cells are susceptible to heat and are believed to die when heated to a temperature of around 43 ° C. Since the affected part of the arm is less reflux than the surrounding part, the affected part of the arm can be heated more easily than the non-circumferential part. Thus, thermotherapy, which selectively heats affected areas of cancer, is an extremely effective cancer therapy.

Conventionally, hot water, infrared rays, ultrasonic waves, microwaves, high frequency, etc. have been tried as a method of locally and selectively heating the cancer affected part of a living body (Japanese Patent Laid-Open Nos. 58-209,530 and 61-158,931). However, no method is effective for deep cancers such as bone tumors.

For example, the living body surface near the occurrence of cancer is pressed between a pair of electrode poles each containing electrodes in saline, and a high frequency current of about 8 kHz is directly applied through the living body across the electrode poles. Methods of heating cancer cells are known. However, the warmer that performs the method can heat only cancer cells that are within about 15 cm from the biological surface. In addition, by heating normal cells as well as cancer cells, if continuous treatment or long-term treatment, there is a problem that adversely affects the normal cells.

Therefore, in order to heat only cancer cells, a method of generating heat in an alternating magnetic field by injecting a ferromagnetic material such as a metal rod, a metal needle, or a metal powder into the affected part of the living body. However, the metal material has high electrical conductivity and easily dissolves in vivo, eluting harmful metal ions, so that the heat generation efficiency is small and not suitable for incorporation in vivo.

Japanese Patent Application Laid-Open No. 57-17647 discloses an example of using ferromagnetic ferrite-containing glass, crystallized glass, and sintered glass as a material for thermal treatment. However, these materials are not excellent in living affinity and are recognized as heterogeneous materials by living environment organisms.

An object of the present invention is a ceramic heating element for introducing into a living body which is harmless and safe even after being put into a living body for a long time, has excellent affinity with surrounding tissues, and can selectively and effectively heat a cancer affected part including a core of the living body. To provide.

1 is a schematic view of a ceramic heating element according to the present invention.

2 is a graph of a magnetization curve showing the heating principle of the ceramic heating element according to the present invention.

3 is a heating curve graph of examples of ceramic heating elements according to the present invention.

4 is a layout view of the ceramic heating element when the temperature rises.

5 is a characteristic diagram showing the result.

The inventor repeated the research experiment, hydroxy apatite, β-3CaO · P₂O₅ Polycrystalline, and essentially Na₂O, CaO, Sio₂And P₂O₅A material such as glass or crystallized glass forms an apatite layer similar to a bone structure on its surface in vivo, and the apatite layer has a very high affinity for living organisms, which naturally binds to surrounding bone structures. I knew that. These materials, even if they do not contain phosphoric acid themselves, incorporate phosphate ions into the biological fluid and deposit apatite (Ca) on their surface.₁₀(PO₄)₆(OH)₂) Form a layer. The apatite layer has excellent affinity with living organisms, and can be directly chemically bonded to bone tissues in vivo, and has excellent affinity with flexible tissues such as muscle and skin. Conventional heating elements in vivo are considered as heterogeneous materials in vivo and covered with fibrous tissue even though they do not dissolve in biological fluids and elute harmful metal ions.

The present invention relates to a ceramic heating element for thermotherapy comprising ferromagnetic ferrite particles and a bioactive inorganic layer around the ferrite particles. By forming, it has a property that is not recognized as a foreign material by the surrounding tissue, and ferrite particles exhibit high efficiency of magnetic induction heating under an alternating magnetic field.

Bioactive inorganic layers include wollastonite, calcium silicate, hydroxyapatite, β-3CaO · P₂O₅ Polycrystalline, Na₂O, CaO, Sio₂And P₂O₅Glass containing as essential constituents, and Na₂O, CaO, Sio₂And P₂O₅It is preferable to become one or more of the crystallized glass which has as an essential component.

Ferromagnetic ferrite particles coated with a bioactive inorganic layer have the feature that the biological tissue does not recognize it as a foreign material. In addition, the coated ferromagnetic ferrite particles have an exothermic function having an exothermic loss in which the exothermic loss is only a magnetic history loss, making it an ideal multifunctional material for thermotherapy.

The ceramic heating element for thermotherapy of the present invention is produced and obtained by at least three methods.

(1) 20 to 90% by weight of ferromagnetic ferrite particles such as magnetite (Fe ₃ O ₄ ), lithium ferrite (LiFe ₅ O ₈ ) and magnesium ferrite (MgFe ₂ O ₄ ), and hydroxyapatite (Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ ) and a powder mixture composition composed of 80 to 10% by weight of bioactive crystal grains such as β-3CaO.P ₂ O ₅ .

In this method, ferromagnetic ferrite is not limited to magnetite, lithium ferrite or magnesium ferrite, and any ferromagnetic ferrite can be used as long as no harmful ions are eluted from biological fluids. However, ferromagnetic ferrite is an essential component that generates heat in the alternating current magnetic field, so it needs to be contained in the composition in an amount of at least 20% by weight in order to obtain a practical calorific value. When the ferromagnetic ferrite is contained in the composition in an amount exceeding 90% by weight, the ferromagnetic ferrite is limited to 90% by weight or less since the ferrite particles are not completely covered with the bioactive material.

Bioactive components such as hydroxyapatite and β-3CaO.P ₂ O ₅ are essential ingredients for ceramic heating elements in order to show good biocompatibility in vivo, and especially when ceramic heating elements are introduced into the body near bone, It is an essential ingredient needed to bind bone. It is preferred to use bioactive crystal grains in an amount of at least 10% by weight in the composition in order to completely coat the ferromagnetic particles with bioactive hard crystal particles. However, when the amount of the bioactive crystal grains exceeds 80% by weight, the calorific value cannot be sufficiently obtained, so the amount of the bioactive particles is limited to 80% by weight or less.

With respect to these components, the composition may contain up to 10% by weight of harmless or beneficial components, such as far infrared radiation.

In order to sinter the composition or mixture of components, any temperature at which the mixture can be sintered may be applied.

(2) magnetite (Fe₃O₄), Lithium ferrite (LiFe₅O₈) And magnesium ferrite (MgFe₂O₄Ferromagnetic ferrite particles such as 20 to 90% by weight, and Na₂10-50 wt% O and CaO, SiO₂And P₂O₅ A method for producing a ceramic heating element for thermotherapy comprising sintering a powder mixture composition composed of 90 to 50% by weight of crystallized glass particles and / or bioactive glass consisting of 90 to 50% by weight.

This method is also not limited to ferromagnetic ferrite, and any ferrite can be used as long as no harmful ions are eluted from the living body. However, the amount of ferrite particles is limited to 20 to 90% by weight of the composition for the same reasons as in method (1).

The bioactive glass and / or the bioactive crystallized glass have a composition in which about 90% by weight consists of 10-50% by weight of Na ₂ O + CaO and 90-50% by weight of SiO ₂ + P ₂ O ₅ .

If the combined amount of Na ₂ O + CaO is less than 10% by weight, the bioactive glass or crystallized glass does not form an apatite layer on the surface in vivo. Moreover, when the sum exceeds 50 weight%, bioactive glass or crystallized glass itself cannot be obtained. Therefore, Na ₂ O + CaO is limited to 10 to 50% by weight.

On the other hand, when the combined amount of SiO ₂ + P ₂ O ₅ is less than 50% by weight, no active glass or crystallized glass can be obtained, and when it exceeds 90% by weight, the bioactive glass or crystallized glass or crystallized glass is in the cotton in vivo Since an apatite layer is not formed, the sum is limited to 90-50 weight%.

The composition may, in addition to the above components, contain up to 10% by weight of no harmless or beneficial components of the far infrared radiation.

Glass particles may be used even if all or part of the crystallization is sintered.

(3) cooling the melt of the composition consisting essentially of 10 to 60% by weight of CaO, 5 to 50% by weight of SiO ₂ , 10 to 80% by weight of Fe ₂ O ₃ , and 0 to 30% by weight of P ₂ O ₅ . A method for producing a ceramic heating element for thermotherapy comprising depositing ferrite particles or cooling the melt to form glass and then reheating to precipitate ferrite particles.

In this method, when the amount of CaO is less than 10% by weight, the glass or crystal phase containing ferrite particles does not show good affinity with the living body, and when the amount of CaO is more than 60% by weight, the composition has a uniform melting point. The melt rises to such an extent that it is difficult to obtain. Therefore, the amount of CaO is preferably limited to 10 to 60% by weight.

When the amount of SiO ₂ is less than 5% by weight, a melt of a uniform composition is not obtained. When the amount of SiO ₂ is greater than 50% by weight, the content of Fe ₂ O ₃ is relatively decreased in the composition. This becomes bad. Therefore, the amount of SiO ₂ is limited to 5 to 50% by weight.

When the amount of Fe ₂ O ₃ is less than 10% by weight, only a small amount of ferrite crystal is precipitated from the application solution, so that good exothermic characteristics are not obtained. When the amount of Fe ₂ O ₃ exceeds 80% by weight, a bioactive glass or crystalline glass containing CaO and SiO ₂ as essential ingredients and having good affinity for living bodies can completely coat the ferromagnetic ferrite particles. Therefore, the amount of Fe ₂ O ₃ is limited to 10 to 80% by weight. In order to precipitate ferrite other than magnetite, a metal oxide of this purpose can be blended with the composition in addition to Fe ₃ O ₄ .

If the amount of P ₂ O ₅ exceeds 30% by weight, only a small amount of ferrite crystal may precipitate from the composition, so that the exothermic properties of the composition are not obtained. However, even if the composition does not contain P ₂ O ₅ , it is possible to form an apatite film on the surface of the body.

In this method, the composition is Li ₂ O, K ₂ O, Na ₂ O, MgO, SrO, B ₂ O ₃ , Al ₂ O ₃ , TiO ₂ , ZrO ₂ , Nb ₂ O ₅ , Ta ₂ O ₅ , It may contain up to 10% by weight of beneficial or additional harmless components, such as CaF ₂ and far infrared radiation. However, when the amount of these components exceeds 10% by weight of the composition, the relative amount of Fe ₂ O _{3 in} the composition decreases and the content of precipitated ferrite particles in the product decreases, resulting in poor exothermic properties, CaO, SiO ₂ Since the content of is decreased, the affinity in the living body is lowered. Therefore, the total amount of the additional components is limited to up to 10% by weight. Therefore, the sum of CaO, SiO ₂ , Fe ₂ O ₃ and P ₂ O ₅ is limited to at least 90% by weight.

When a limited range of composition melts are cooled at relatively low cooling rates, ferromagnetic ferrite particles may precipitate out of the application liquid during cooling. By appropriately selecting the cooling rate, the amount and diameter of the ferrite particles can be properly adjusted. By appropriately adjusting the amount and diameter of the ferrite particles, it is possible to appropriately control the exothermic properties of the composition. When the application liquid is quenched or quenched, glass can be obtained and the ferrite particles can be precipitated by reheating the glass. The heating temperature at which the ferromagnetic ferrite particles are precipitated can be known by preliminary measurement of the exothermic peak of the differential thermal analysis of the glass. By appropriately selecting the heating conditions, the amount and diameter of the precipitated ferrite particles can be properly adjusted, so that the exothermic properties of the composition can be appropriately controlled.

When the melt is cooled to precipitate ferrite or when the glass obtained from the melt is heated to precipitate ferrite, wollastonite (CaO · SiO ₂ ), calcium silicate (2CaO · SiO ₂ ), or apatite (Ca ₁₀ (PO ₄ ) ₆ Crystals other than ferrite such as (OH) ₂ ) can be precipitated without obstacles. The phase covering the ferrite particles depends on the cooling conditions of the application liquid and the heat treatment conditions of the glass. The above may be a glass phase, wollastonite (CaO · SiO ₂ ), calcium silicate (2CaO · SiO ₂ ), apatite phase, hydroxyapatite phase, or a mixed phase thereof, and any phase as long as the film of apatata can be formed on the surface. May be used for the purposes of the present invention. When additive components such as LiO ₂ , Na ₂ O, K ₂ O, and MgO are added to the application liquid, crystals other than the above-described crystals may be precipitated.

As described above, the ceramic heating element of the present invention is characterized in that the ferromagnetic ferrite particles are coated with a bioactive inorganic layer that shows excellent affinity with surrounding tissues in vivo and is safely maintained for a long time.

The induction-heated ceramic heating element of the present invention may be used in the form of fine powder, molded body, or fibrous, and is transferred to the cancerous part of the living body by intravenous injection, subcutaneous injection, oral administration or landfill surgery, depending on the shape thereof, and then the cancerous part It is disposed in the alternating magnetic field, and the ferromagnetic ferrite particles are heated by the magnetic history loss to heat-treat the affected area.

The present invention will be described with reference to the accompanying drawings.

The present invention will now be further described with reference to Examples.

Example 1-24

Examples of the method of manufacturing the ceramic heating element for thermotherapy according to the present invention are shown in Tables 1,2 and 3. Table 1 of Tables 1-3 is an Example corresponding to Claim 1 of Claim.

In Tables 1 and 2, the mixing ratio of the bioactive inorganic layer and the ferrite particles is selected 1: 1 for convenience, but the present invention is not limited thereto.

Apatite used in Examples 1 to 3 of Table 1 is prepared by reacting slaked lime with phosphoric acid in an aqueous solution.

Ferrite particles are synthesized by a wet method. When the ferrite particles are Fe ₃ O ₄ Fe ₃ O _{4 It} is prepared by the following method. Iron sulfate is reacted with an oxygen stream in an aqueous 80% sodium hydroxide solution. After about 1 day, the reaction is stopped and the reaction iron sulfate or Fe ₃ O ₄ is washed well with water, dried and mixed with stearic acid. Apatite and Fe ₃ O ₄ fine particles are uniformly mixed using a mixer, then molded at a pressure of 400 kg / cm ² and sintered in an N ₂ air stream. When the ferrite particles are LiFe ₅ O ₈ or MgFe ₂ O ₄ , the molded body can be sintered in air.

In Example 4 of Table 1, β-3CaO.P ₂ O _{5 used} was prepared by adding calcium salt and ammonia to an aqueous sodium phosphate solution to form a precipitate, and drying the precipitate. Ferrite was manufactured by the same mixing and drying method as in Examples 1 to 3.

In Examples 5-7 of Table 2, A-W crystallized glass is manufactured by the method of Japanese Unexamined-Japanese-Patent No. 62-10,939. Ferrite is manufactured by the same mixing and drying method as in Examples 1 to 3 in Table 1. The apatite-containing crystallized glass of Example 8 of Table 2 was prepared by U.M. Gross and V. Strunz. J. Biomed. Mater. Res. It is prepared based on the method described in 14 (1980) 607. Ferrite was manufactured by the same mixing and drying method as in Examples 1 to 3 of Table 1.

In _{1600 ℃ Na 2 CO 3, CaCO} 3, SiO 2 and Ca ₂ of P ₂ O ₇ Example 9 A commercially available melt the reagent powder mixture is referred to quantize direct the molten mixture because magnetizing the molten mixture of the standing table 2 Na ₂ O A -CaO-SiO ₂ -P ₂ O ₅ glass and a CaO-SiO ₂ glass of Example 10 of Table 2 were prepared. Ferrite was manufactured by the same mixed drying method as in Examples 1 to 3 of Table 1.

One end corresponding to the compositions of Examples 11 and 12 in Table 3 was prepared using raw materials of oxides, carbonates, hydroxides or fluorides and placed in a platinum crucible to melt 1,300 to 1,550 ° C. This melt flows into a mold 5 mm deep located on the heater. Then, the electric current of the heater is controlled to cool at a controlled cooling rate to precipitate ferrite particles during cooling of the melt. In this method, relatively large ferrite crystals having a diameter of about 1 μm are more easily obtained than once crystallized after glass is described later.

One end corresponding to the composition of Examples 13 to 24 of Table 3 is prepared using a raw material of an oxide, carbonate, hydroxide, or fluoride, placed in a platinum container, and applied in a converter for 2 hours at a temperature of 1,300 to 1,550 ° C. Next, the molten liquid is cast on an iron plate or sandwiched between a pair of rotary rollers and cooled to prepare a glass. After pressing the powder to a predetermined shape, the powder is heated in an electric furnace to a ferrite precipitation temperature (about 1,000 ° C.) at an elevated temperature of 5 ° C./min, and ferrite precipitates at the target precipitation temperature, and then the power source is turned off. Disconnect and leave the converter cool. The same result is obtained when the glass is heat-treated in the shape of a plate without grinding the glass.

All ceramic heating elements obtained by the above three methods have a structure in which ferromagnetic ferrite particles are embedded in the bioactive inorganic layer. In Fig. 1, the? Marks indicate ferromagnetic ferrite particles, and the others indicate parts of bioactive inorganic solids. The ceramic heating element thus obtained was pulverized and its magnetization characteristics were measured using a sample vibration magnetometer (VSM-3 type) under various magnetic field ranges of ± 100 to ± 500Oe. The magnetization characteristics of the heating element of the composition of Example 13 in Table 3 are shown in FIG. The same measurement is performed on a heating element of the composition of Example 14. Based on this result, the calorific value p of the magnetic field of various intensity at 100 KHz is measured from the following equation and the result shown in Fig. 3 is obtained:

Where f is the frequency (Hz), H is the strength of the magnetic field, and B is the magnitude of the magnetization (emu / g). As can be seen in FIG. 3, the heating element of Example 14 has a higher calorific value at a lower magnetic field than the heating element of Example 13. This is because the heating element of Example 14 has a lower coercive force and greater saturation magnetization than the heating element of Example 13.

2 g of the ceramic heating element particles of Example 13 having a particle size of 350 mesh (44 μm) were embedded in the center of an agar having a size of 40 mm x 110 mm, and placed in the center of an air-core coil having a length of 240 mm. A maximum current of 5 kW is applied in a 100 kHz magnetic field, and the temperature change of the heating element is measured with a copper-constantan thermocouple inserted in the center of the coil. Specific heat and density of agar approximates living tissue. It is clear from this experiment that the temperature at the center of the heating element reaches 43 ° C within about 5 minutes after the first application of current under a magnetic field of 170Oe. Then, 3 g of particles of the heating element are embedded in the center of the dead pig vertebra shown in FIG. 4, and the thermocouples are placed at positions a, b, c, d and e as shown in FIG. Landfill

The whole agar was placed in the air core coil in the same manner as described above, and the temperature change was measured at each thermocouple position by applying a current of up to 5 kW in a 100 kHz magnetic field. When a current of 3 kW is applied under a magnetic field of 150Oe in FIG. 5, the temperature change at each of positions a, b, c, d and e in FIG. 4 is shown. As can be seen in Figure 5, in the same way as Figure 4 can be heated to a temperature of 41 ~ 44 ℃ the temperature required to kill cancer cells.

As is apparent from the foregoing description, the induction heating element for thermotherapy according to the present invention has excellent heating properties and good affinity for living organisms, and is particularly effective for deep cancer of bone tumors, and eluting harmful ions such as metal ions. It is not effective for treating cancer lesions continuously for a long time.

While the invention has been described in terms of specific embodiments and numbers, various changes and modifications of the invention are possible without departing from the broad technical spirit of the invention as defined by the appended claims.

Claims (1)

As a method of manufacturing a ceramic heating element for thermotherapy, 20 to 90% by weight of ferromagnetic ferrite particles such as magnetite (Fe ₃ O ₄ ), lithium ferrite (LiFe ₅ O ₈ ) and magnesium ferrite (MgFe ₂ O ₄ ), and hydroxy For thermotherapy characterized in that the powder mixture composition composed of 80 to 10% by weight of bioactive crystal grains such as apatite (Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ ) and β-3CaO.P ₂ O ₅ Method for producing a ceramic heating element.