JP2599619B2 - Hyperthermia implant material - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a magnetic material for heating a living body, and more particularly, to the use of a temperature-sensitive amorphous alloy in hyperthermia, which is one type of a method for treating malignant tumors such as cancer. The present invention relates to a local heating implant material.

[Prior art] Focusing on the difference in heat sensitivity between malignant tumor cells such as cancer and normal cells, a method of treating cancer by heating the temperature near the tumor to 42 ° C. or more ( (Hyperthermia) began to be studied around 1960, and recent remarkable advances in heating technology have been applied to a wide range of applications. Hyperthermia is roughly classified into whole body hyperthermia and local hyperthermia according to its heating means.

Hot water or molten paraffin is used for whole body hyperthermia, and extracorporeal circulation blood warming is the most widespread in Japan.

Local hyperthermia often uses electromagnetic waves, such as microwave heating (2,450 MHz, 915 MHz, 434 MHz, etc.), RF induction heating (27.12 MHz, 13.56 MHz), and RF dielectric heating (13.56 MHz, 8M)
Hz) and ultrasonic heating (1-3 MHz) have been approved by the Ministry of Health and Welfare for clinical applications. In particular, the RF dielectric heating device has become the mainstream for Japanese with less subcutaneous fat.

In principle, microwave heating has a heating limit from the epidermis to a depth of several centimeters, and is effective only for superficial tumors. RF dielectric heating selectively heats the area around the electrodes and subcutaneous fat, making it difficult to heat only the affected area. Further, in the RF induction heating, deep heating is possible, but there is a drawback that a heat generation pattern is easily disturbed by non-uniform impedance in a living body, and other than a lesion is heated. Further, the heating by ultrasonic waves has good convergence and is suitable for local heating in a deep part, but there is a limitation on the application site because it is reflected on a boundary surface between bone and air.

Although the methods described above have the advantage of being non-invasive with respect to heating, it is not easy to reliably achieve local warming of a deep part of a living body. Therefore, in order to prevent the occurrence of a hot spot (Hot Spot) in an unnecessary place, it is necessary to constantly measure the temperature, and as a result, it becomes invasive. Furthermore, the location of the occurrence of hot spots is difficult to predict, and an appropriate temperature distribution measurement method has not yet been established. In general, when electromagnetic waves are used, local heating is possible if the frequency is increased, but deep heating is difficult.If the frequency is reduced, the deep heating is facilitated but the heating range is widened. Have a problem.

In recent years, a method called a soft heating method has been developed to cover the problems of these electromagnetic wave application hyperthermia. In this method, a temperature-sensitive magnetic material is embedded in a tumor part in a living body, and a hysteresis loss or the like generated by excitation with a high-frequency alternating magnetic field is used as a heat source.

As the implant material used in this soft heating method, any of the temperature-sensitive magnetic materials (ferrite, Ni-Si, Fe ₃ C, etc.) that have been conventionally studied have poor heating efficiency at around normal temperature, and It is not easy to maintain the stable temperature required for treatment. In order to improve these practical characteristics, a composite heating element using a combination of a magnetic material and a non-magnetic material has been devised. However, the number of instability factors has increased, and the characteristics leading to practical use have not yet been obtained.

Recently, it has been proposed to use amorphous alloy powders as implant materials for hyperthermia ("Bi
omedical Thermography ", Vol. 7, No. 1, pp. 7-10, 198
7 years). This implant material is buried in an agar phantom, inserted into a cancerous site deep in a living body, and induction-heated by a high-frequency magnetic field.

[Problems to be solved by the invention]

However, since the amorphous alloy used for this implant material has a high Curie temperature of several hundred degrees Celsius, when an external alternating magnetic field is applied, the temperature becomes too high, exceeding about 45 ° C. Therefore, in order to set the affected part to a desired temperature, it is necessary to control the external magnetic field and adjust the temperature. However, there is a problem that the heating therapy is complicated because the heating state differs depending on the position and the state of the affected part and it is necessary to adjust while accurately detecting the temperature of the affected part.

Therefore, an object of the present invention is to provide an implant material that can always induce and heat an affected part to a predetermined temperature range without requiring special control.

[Means for solving the problem]

In light of the above objects, as a result of intensive research, the present inventors have found that adding the Cr and / or Mo to the amorphous alloy composition system reduces the Curie point to a desired level.
The present inventors have discovered that the heating temperature of the amorphous alloy can always be maintained at a desired level of about 42 to 45 ° C. without controlling the external alternating magnetic field in the induction heating, and completed the present invention.

That is, the implant material for thermotherapy of the present invention,
10 to 30 atomic% of one or more semimetals of P, C, Si and B, 12 to 13 atomic% of Cr and / or Mo, and one or more transitions of Fe, Ni and Co It has a composition consisting of metal, has a Curie temperature of 42 ° C to 90 ° C, and has a thickness of 15 to 40.
It is characterized in that a non-magnetic container is filled with a temperature-sensitive amorphous alloy powder having an average diameter of 297 μm or more.

The present invention will be described in detail below. The implant material for thermotherapy of the present invention is obtained by filling a non-magnetic container with a thermosensitive amorphous alloy powder.

The basic composition of the amorphous alloy used in the present invention is (Fe, Ni, Co) M ₁ M ₂ (where M ₁ is Cr and / or Mo, and M ₂ is P, C, Si
And B are one or more metalloids. ).

A M ₁ Cr and / or Mo is an element added for the purpose of lowering the Curie temperature, also impart corrosion resistance simultaneously.
In particular, a decrease in the Curie temperature is important as a magnetic material for soft heating, and local heating to a malignant tumor treatment temperature,
And a treatment temperature can be maintained.

Curie temperature should be in the range of 42-90 ° C. 42
If the temperature is lower than 0 ° C, the temperature cannot be heated to a temperature range effective as a hyperthermia, and if the temperature is higher than 90 ° C, the inductance reduction temperature exceeds 55 ° C, and the treatment temperature range is exceeded, resulting in overheating. The preferred Curie temperature is 60-75 ° C. M ₁ for such purpose is about 12 to 13 atomic% in the alloy.

Semimetal M ₂ is P, C, Si, about 10 to 30 atomic% in the alloy at one or more of B.

The temperature-sensitive amorphous alloy is preferably in a powder form so that it can be formed into a desired shape as an implant material.
As the particle size of the amorphous alloy powder becomes smaller, the heating curve becomes gentler, and it takes more time to heat the affected part to a desired temperature. Therefore, when the amorphous alloy powder has a flat shape with a thickness of about 15 to 40 μm, the average diameter (length) is preferably 297 μm or more.

Such an amorphous alloy powder can be obtained by pulverizing a ribbon or flake produced by a usual melting and quenching method (single roll method, double roll method, cavitation method, etc.).

[Action]

Since the implant material for thermotherapy of the present invention uses an amorphous alloy having a relatively low Curie temperature, a heating curve is leveled around a heating treatment temperature, and has a property of not heating even if it is further excited. This leveled temperature is slightly lower than the Curie temperature, but rather corresponds to a sudden drop in inductance in coil excitation. Due to such properties, the temperature of the amorphous alloy does not rise to a certain temperature or more without controlling the external excitation, and stable heating treatment can be performed.

〔Example〕

 The present invention is described in more detail by the following examples.

Example 1 From a molten metal having a composition of Fe _66.8 Cr _13.2 P _13.2 C _6.8 (atomic%), a thickness of 15 to 25 μm was obtained by a cavitation method.
m, amorphous flakes having a length in the range of 500 to 1000 μm were prepared and pulverized to produce flat powders having a length of 63 to 1000 μm. The Curie temperature of the obtained amorphous alloy powder is 64 ° C, the crystallization temperature is 470 ° C, and the saturation magnetic flux density Bs is 420.
It was 0G.

This powder was classified to obtain a sample having the following particle size range.

Sample No. Particle size (μm) 163 to 149 2 149 to 297 3 297 to 500 4 500 to 1000 As shown in FIG. 1, each sample is filled in a non-magnetic pipe 1 having an inner diameter D6 mm and a length L50 mm. , 50 on the outer circumference of pipe 1
Wind the winding coil 2 for excitation at a frequency of 100 KHz and 2.
An alternating magnetic field of 0 KA / m was applied. FIG. 2 shows the boundary temperature characteristics of each sample. From FIG. 2, it can be seen that as the particle size increases, the rate of temperature rise increases, and the temperature control characteristics become more stable, reflecting the decrease in the demagnetizing coefficient.
The control temperature here is 41 ~ 44 ℃, Curie temperature 64 ℃
About 20 ℃ lower.

Next, FIG. 3 shows the inductance at each temperature for each particle size. It can be seen that the inductance decreases rapidly, that is, the impedance decreases at 40 to 45 ° C.

This indicates that the temperature rise control characteristics of the sample of the example depend not on the Curie temperature itself but on the temperature change of the inductance.

Example 2 An amorphous alloy powder having a composition of Fe _80-x Cr _x P ₁₃ C ₇ (atomic%) was produced in the same manner as in Example 1. The particle size of the powder was 63-1000 μm. FIG. 4 shows the results of measuring the Curie temperature Tc, the magnetic flux density B _10k at 10 KOe, and the magnetic flux density B ₁₀₀ at ₁₀₀ Oe for the samples having each Cr content.

FIG. 4 shows that as the Cr content increases, the Curie temperature Tc of the alloy decreases and B _10k and B ₁₀₀ also decrease. In order for Tc to be in the range of 42-90 ° C,
The Cr content in this system is 11.5-13.7 atomic%.

〔The invention's effect〕

As described above in detail, the implant material for hyperthermia of the present invention uses a temperature-sensitive amorphous alloy having a Curie point as low as 42 to 90 ° C., so that even when the external magnetic field is increased, the predetermined temperature or more correlated with the Curie temperature. It is not heated. Therefore, the temperature of the affected part, such as cancer, can always be kept at a desired level without requiring special control, and this is effective for induction-type therapy such as cancer treatment.

[Brief description of the drawings]

FIG. 1 is a schematic diagram showing an apparatus for measuring the temperature-raising characteristics and magnetic characteristics of a temperature-sensitive amorphous alloy powder used in the present invention, and FIG. 2 is a temperature-sensitive amorphous alloy powder used in the present invention. FIG. 3 is a graph showing the relationship between the particle size and the temperature-rise characteristics of FIG. 3, FIG. 3 is a graph showing the temperature dependence of the inductance of the temperature-sensitive amorphous alloy powder used in the present invention, and FIG. 4 is a graph showing the relationship between the Cr content of the thermosensitive amorphous alloy powder used, the Curie temperature, and the magnetic flux densities B _10k and B ₁₀₀ . 1 Non-magnetic pipe 2 Excitation coil

Claims (1)

(57) [Claims] (1) one or more semimetals of at least one of P, C, Si and B: 10 to 30 atomic%, Cr and / or Mo: 12 to 13 atomic%,
Thermosensitive amorphous having a composition consisting of one or more transition metals of Fe, Ni and Co, a Curie temperature of 42 ° C to 90 ° C, a thickness of 15 to 40 μm and an average diameter of 297 μm or more An implant material for hyperthermia, wherein an alloy powder is filled in a non-magnetic container.