JPH04116146A - Temperature-sensitive amorphous alloy coated with polymer - Google Patents

Abstract

PURPOSE:To prevent an allay constituted of transition metals and semimetals and having a low Curie temp. from heating to a prescribed temp. or above when it is used for thermotherapy and to secure the safety of living bodies by coating the surface of the above alloy with a resin. CONSTITUTION:This amorphous allay is formed by coating the surface of an alloy with 42 to 90 deg.C Curie temp. with a polymer resin harmless to living bodies. The above alloy is formed from a compsn. constituted of transition metals selected from Fe, Ni and Co and semimetals selected from P, C, Si and B. At the time of using this amorphous alloy to an inplant material for local heating, even in the case an external magnetic field is increased, it is not heated to a prescribed temp. or above, and, by the coated resin, the flow of metallic ions into living bodies is prevented to secure the safety of living bodies.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to a magnetic material for biological heating, and more specifically, in hyperthermia, which is a type of treatment for malignant tumors such as cancer, as an in-bran mill material for local heating. The present invention relates to a temperature-sensitive amorphous alloy that can be used.

[Prior Art] Focusing on the difference in heat sensitivity that exists between malignant tumor cells such as cancer and normal cells, cancer treatment is carried out by heating the temperature near the tumor to 42°C or higher. Research into the method of heating (hyperthermia) began around the 1960s, and with recent remarkable advances in heating technology, a wide range of applications are being attempted. Hyperthermia is broadly classified into whole body thermotherapy and local thermotherapy depending on the heating method used.

Whole body thermotherapy uses warm water and melted paraffin.
In Japan, extracorporeal circulation blood warming is the most popular method.

Local heat therapy often uses electromagnetic waves, such as microwave heating (2,450MHz, 915MHz, 43
4MHz, etc.), RF induction heating (27, 12MHz, 1
3.56MHz), RF dielectric heating (13,56MHz
, 8MIIz) and ultrasonic heating (1-3 MHz)
Various external warming devices based on the above have been approved by the Ministry of Health and Welfare for clinical use. In particular, RF dielectric heating devices are the mainstream for Japanese people who have little subcutaneous fat.

In principle, microwave heating can only be heated to a depth of several centimeters from the epidermis, and is effective only for superficial tumors. In RF dielectric heating, the area around the electrode and subcutaneous fat are selectively heated, making it difficult to heat only the affected area. Also, RF
Although induction heating allows deep heating, it has the disadvantage that the heat generation pattern is likely to be disrupted due to nonuniform impedance within the body, and areas other than the lesion are also heated. Furthermore, heating by ultrasonic waves has good convergence and is suitable for deep local heating, but there are limits to the areas where it can be applied because it is reflected at the interface with bones and air.

Although the methods described above all have the advantage of being non-aggressive in terms of heating, it is not easy to reliably achieve local heating deep within the body.

Therefore, high temperature areas (1 (ot 5 pots)
), it is necessary to constantly measure the temperature, which can be invasive. More flot 5po
The location where t occurs is difficult to predict, and an appropriate temperature distribution measurement method has not yet been established. Also, generally when using electromagnetic waves,
If the frequency is increased, local heating is possible but deep heating becomes difficult, and if the frequency is lowered, deep heating becomes easier but the heating range becomes wider, which is an essential problem.

In order to overcome these problems with electromagnetic wave-applied hyperthermia, a method called the soft heating method has been developed in recent years. In this method, a temperature-sensitive magnetic material is implanted into a tumor in a living body, and a high-frequency alternating magnetic field is applied. The hysteresis loss generated by excitation is used as a heat source.

Temperature-sensitive magnetic materials (ferrite, Ni-5i, Fe5C, etc.) that have been considered as implant materials for this soft heating method all have poor heating efficiency near room temperature, and are difficult to treat. Maintaining the stable temperature required for this is not easy. In order to improve these practical characteristics, composite heating elements made by combining magnetic and non-magnetic materials have been devised, but there are many instability factors and the characteristics that lead to practical use have not yet been achieved.

Recently, it has been proposed to use amorphous alloy powder as a hyperthermia implant material (rB
iomedical thermography J
XVof! ,.

7, No. 1.7-10, 1987). This implant material is embedded in an agar phantom, inserted into a cancerous area deep within a living body, and heated by induction using 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, above about 45°C. Therefore, in order to set the affected area to a desired temperature, the external magnetic field must be controlled to adjust the temperature. However, the heating state differs depending on the location and condition of the affected area, and the temperature of the affected area must be accurately detected and adjusted, making the heating therapy complicated.

Therefore, an object of the present invention is to provide a temperature-sensitive amorphous alloy whose main body is coated with a harmless polymer resin for use as an implant material, which can constantly induce and warm the affected area to a predetermined temperature range without requiring special control. It is to be.

[Means for Solving the Problems] As a result of intensive research in view of the above objectives, the present inventors have found that by increasing Nil in the composition system of an amorphous alloy, the Curie temperature can be lowered to a desired level.
It has been discovered that the heating temperature of an amorphous alloy can be constantly maintained at a desired level of about 42 to 45°C without controlling an external alternating magnetic field during induction heating, and this has been disclosed in JP-A-2-52663 and JP-A-2-52663. The present invention was completed by further improving the magnetic materials disclosed in JP-A No. 2-47243.

That is, the temperature-sensitive amorphous alloy for thermotherapy of the present invention comprises one or more transition metals of Fe, Ni, and Co, and one or more semimetals of P, C, Si, and B. and has a Curie temperature of 42°C to 90°C,
It is characterized in that the surface of the a'1 fill amorphous alloy is coated with a polymer resin.

Furthermore, the present invention shows that when the Curie point is lowered to a desired level by adding Cr and/or Mo to the composition system of the amorphous alloy, the amorphous alloy can be heated without controlling an external alternating magnetic field during induction heating. heating temperature 4
A desired level of about 2 to 45°C can be maintained at all times.

That is, the temperature-sensitive amorphous alloy for thermotherapy of the present invention comprises one or more transition metals of Fe, Ni, and Co, and one or more semimetals of P, C, Si, and B. , Cr and /Mo, has a Curie temperature of 42° C. to 90° C., and is characterized in that the surface of the temperature-sensitive amorphous alloy is coated with a polymer resin.

The present invention will be explained in detail below.

The basic composition of the amorphous alloy of the present invention is (Fe, Ni,
Co) (P, C, Si, B).

Ni is an element added for the purpose of lowering the Curie temperature, and at the same time imparts corrosion resistance. In particular, lowering the Curie temperature is important as a magnetic material for soft heating.
This enables local heating to a temperature for treating malignant tumors and maintenance of the treatment temperature.

Furthermore, by adding Al2 to the above composition, the Curie temperature can be further lowered.

Therefore, AI! , an amorphous alloy with a low Curie temperature can be obtained even if the amount of Ni added is suppressed. In general, increasing the amount of Ni added tends to reduce the magnetic flux density of amorphous alloys, but if the amount of Ni added is suppressed by adding Al as described above, an amorphous alloy with a low Curie temperature and a small decrease in magnetic flux density can be produced. Alloys can be obtained.

The Curie temperature needs to be in the range of 42-90°C.

This is because if the temperature is 42°C or lower, it cannot be heated to a temperature range effective for hyperthermia, and if it is 90°C or higher, the inductance reduction temperature exceeds 55°C, exceeding the therapeutic temperature range and resulting in overheating.

For this purpose, Ni is about 40 to 50 atomic % in the Aj2-added alloy, and about 55 to 65 atomic % in the Af-free alloy. Naohe! In the case of additive alloys, the amount of l added is 2~
Preferably, it is 5 atom %.

The content of one or more metalloids of P, C, Si, and B is about 10 to 30 atomic % in the alloy.

When the obtained amorphous alloy powder is coated with a nonmagnetic metal, the temperature increase rate during induction heating can be increased.The nonmagnetic metal is preferably a metal with good electrical conductivity such as Cu, Ag, or Au. This is because it increases the skin effect in an alternating magnetic field and improves the temperature rise characteristics during heating by generating heat due to the eddy current product.

The thickness of the non-magnetic metal film is preferably equal to or less than the thickness of the temperature-sensitive amorphous alloy powder, and a film thickness of 5 μm to 10 μm is particularly preferred. If the film thickness is thin, the improvement in temperature rise characteristics during heating will be weak, and if the film thickness is thick, the actual filling rate of the amorphous alloy itself will decrease, and the constant temperature part of the heating curve (p
lateau) become unclear.

Such amorphous alloy powder can be produced by a normal melting and quenching method (single roll method, double roll method, cavitation method, etc.) or by pulverizing chips or flakes.

Furthermore, it can be obtained by coating the surface of a temperature-sensitive amorphous alloy with a polymer resin that is harmless to living organisms by chemical, physicochemical, or physical methods.

Furthermore, the basic composition of the amorphous alloy of the present invention is (Fe
, Ni, Co) M+Mz (however, H3 is Cr and/or Mo, M2 is P
, C, Si and B or two or more metalloids.

).

Cr and/or Mo, which is h, is an element added for the purpose of lowering the Curie temperature, and at the same time imparts corrosion resistance. In particular, a reduction in the Curie temperature is important as a magnetic material for soft heating, and enables local heating to a temperature for treating malignant tumors and maintenance of the treatment temperature.

The Curie temperature needs to be in the range of 42-90°C.

This is because if the temperature is 42°C or lower, it cannot be heated to a temperature range effective for hyperthermia, and if it is 90°C or higher, the inductance reduction temperature exceeds 55°C, exceeding the therapeutic temperature range and causing overheating.

For such purposes 11. is about 12 to 13 atomic % in the alloy.

The semimetal F'I2 is one or more of P, C, Si, and B and accounts for about 10 to 30 atomic percent in the alloy.

Non-magnetic metals for increasing the induction heating rate include Cu,
Metals with good electrical conductivity such as Ag and Au are preferred. This is because it increases the skin effect in an alternating magnetic field and improves the temperature rise characteristics during heating due to heat generation due to eddy current. The thickness of the film is preferably equal to or less than the thickness of the amorphous flakes, and a film thickness of 5 μm to 10 μm is particularly preferred. If the thickness is small, the improvement in the heating characteristics is weak, and if the thickness is large, the actual filling rate of the amorphous alloy itself decreases, and the constant temperature plateau of the heating curve becomes unclear.

The temperature-sensitive amorphous alloy of the present invention is preferably in powder form so that it can be molded into a desired shape as an implant. 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 area to the desired temperature. However, by coating the surface of the temperature-sensitive amorphous alloy powder with a non-magnetic metal, the rate of temperature rise when an alternating magnetic field is applied can be significantly improved.

Such amorphous alloy powder can be produced by normal melting or
It can be obtained by crushing ribbons or flakes produced by cold processing (single roll method, double roll method, cavitation method, etc.).

In general, it can be obtained by coating the surface of the temperature-sensitive amorphous alloy with a polymer resin that is harmless to living organisms by chemical, physicochemical, or physical methods.

[For production]

Since the amorphous alloy of the present invention has a relatively low Curie temperature, it has the property that the heating curve becomes flat near the heating treatment temperature, and the temperature does not rise even if it is further excited. This leveled temperature is slightly lower than the Curie temperature, and rather corresponds to the temperature at which the inductance rapidly decreases in the case of coil excitation. Due to this property, the temperature of the amorphous alloy never rises above a certain temperature even without controlling external excitation, and stable heating treatment can be performed. By coating the amorphous alloy powder with a non-magnetic metal such as copper or silver, the temperature increase rate can be sufficiently increased. Furthermore, by coating the surface of the amorphous alloy with a polymer resin, it is possible to prevent the outflow of metal ions that are harmful to the living body, thereby ensuring the safety of the living body.

That is, the temperature-sensitive amorphous alloy itself has corrosion resistance.Although the amorphous alloy itself has corrosion resistance, since its surface is metal, metal ions may leak into living organisms, which may be harmful to living organisms. In the present invention, the outflow of metal ions is prevented by a polymer coating.

Regarding the outflow of metal ions, the following facts have been confirmed through the following tests.

Stir in physiological saline at 37°C for 8 hours.
Table 1 shows the observation results of the corrosion weight loss and outflowing metal ions after 3 weeks of repeating the cycle of standing for a period of time every day.

In the Fe-Cr amorphous alloy, the corrosion weight loss is zero, but the corrosion in the living body does not match the ionization tendency, and a complicated reaction progresses. In other words, when a metal is placed in a living body, the damage to cells caused by it varies depending on the strength and type of chemical reaction between the body fluid and the metal. For example, Ni in the T1Ni memory alloy is carcinogenic and allergenic, and the safety of metals to living organisms cannot be determined by a simple corrosion test. but,
With noble metals that have a smaller tendency to ionize than hydrogen, a polymer film is formed that suppresses the ionization of the metal.
Noble metals are used as in-vivo materials.

Amorphous alloys coated with polymers are similar to noble metals forming polymer films in vivo, and are effective as in vivo materials.

(Example) The present invention will be explained in further detail by the following examples.

1 soup Fe + 7. z Nii+o, 6Si++, 7B+z, a
(at.
Amorphous flakes with a length in the range of 0 μm were prepared, and flattened powder with a length of 63 to 1000 μm was produced by pulverization. The Curie temperature of the obtained amorphous alloy powder is 65
C.1 crystallization temperature was 520.degree.

The above amorphous alloy powder was mixed with polymer particles harmless to living organisms, and the mixture was heated and dried to coat the surface of the amorphous alloy powder with a polymer resin. In order to uniformly coat the surface of the amorphous alloy with polymer particles, it is desirable that the particle size of the polymer particles is 0.2 to 0.8 μm.

This powder was classified to obtain samples having the particle size range shown below.

Sample No. Particle size (μm) 1 63-149 2 149-297 3 297-500 4 500-1000 As shown in Figure 1, inner diameter D 6 mm, length L 50 m
Fill each sample into non-magnetic pipe 1 of m, and pipe 1
A 50-turn excitation coil 2 is wound around the outer circumference of the 2. An alternating magnetic field of OKA/m was applied. FIG. 2 shows the temperature rise characteristics for each sample not coated with a non-magnetic metal, and FIG. 3 shows the temperature rise characteristics for each sample coated with a non-magnetic metal. From FIG. 2, it can be seen that as the particle size increases, the temperature increase rate becomes faster and the temperature control characteristics become more stable, reflecting the decrease in the demagnetizing field coefficient. The control temperature here is 63-68°C,
This almost coincides with the Curie temperature of 65°C.

Next, FIG. 4 shows the inductance at each temperature for each particle size, and it can be seen that a sudden decrease in inductance, that is, a decrease in impedance occurs at 40 to 45 degrees Celsius.

From this, it can be seen that the temperature increase control characteristic of the sample of the example is approximately the Curie temperature, and is greatly influenced by the temperature change of the inductance.

Actual picture I L Fll, +l]-+ Ni, 5ino B10 (alloy A), FeaG-y, N1yP10 BIG
(alloy B) and F(-ts-x Nix PI6 B6
An amorphous alloy powder having a composition (atomic %) of 813 (alloy C) was produced in the same manner as in Example 1. The particle size of the powder was 63-11000u. The results of measuring the Curie temperature Tc for each Ni content sample are shown in the fifth column.
As shown in the figure.

It can be seen from FIG. 5 that the Curie temperature Tc of the alloy decreases as the Ni content increases. Tc is 42-9
In order to be within the range of 0°C, the Ni content in each prefecture must be 59.0 in the case of Fe-Ni-3i-B system (alloy A).
~62.3 at%, and in the case of Re-N1-P-B system (alloy B) it is 60.8-63.9 at%, and Fe-N
44.3 to 49 for 1-P-B-Δρ system (alloy C).
It is 4 atom%. That is, by adding 3 atomic % of i, the amount of Ni added can be reduced by 15 to 20 atomic %.

This makes it possible to suppress a decrease in the saturation magnetic flux density of the amorphous alloy.

Actual force I forceps 1 Febb,, lCr++, zPt:+, zCb, a (
From a molten metal having a composition of
Amorphous flakes with a length of 63 to 1000 μm were produced by pulverization to produce flat powder with a length of 63 to 1000 μm. The Curie temperature of the obtained amorphous alloy powder is 44℃1
Crystallization temperature is 470℃ 1 Saturation magnetic flux density Bs is 4200G
Met. The above amorphous alloy powder and polymer resin were mixed and dried by heating to coat the surface of the amorphous alloy powder with the polymer resin. In order to uniformly coat the surface of the amorphous alloy with the polymer, it is desirable that the particle size of the polymer particles is 0.2 to 0.8 μm.

The polymer-coated powder and the non-polymer-coated powder were classified, respectively, to obtain samples having the following particle size ranges.

Sample No., particle size (μm) 1
63-149 2 149-297 3 297-500 4 500-1000 As shown in Fig. 1, inner diameter D 6 mm, length L 50 m
Fill each sample into non-magnetic pipe 1 of m, and pipe 1
An excitation coil 2 of 50 turns was wound around the outer circumference of the tube, and an alternating magnetic field of 2.0/m was applied at a frequency of 100 KHz. FIG. 2 shows the temperature rise characteristics for each sample not coated with polymer. FIG. 7 shows a comparison of the temperature rise characteristics of Powder Sample No. 1 coated with polymer and a sample of the same particle size that is not coated with polymer. No change in temperature increase characteristics was observed due to coating with polymer.

It can be seen from FIG. 6 that as the particle size increases, the temperature increase rate becomes faster and the temperature control characteristics become more stable, reflecting the decrease in the demagnetizing field coefficient.

An amorphous alloy powder having a composition of Feao-1Cr and PI3C7 (atomic %) was produced in the same manner as in Example 3. The particle size of the powder was 63-1000 μm.

Curie temperature Tc1 for each Cr content sample
Magnetic flux density BIOk at 10KOe, and 1000e
The magnetic flux density B1° at Figure 8 shows the measurement results.

From FIG. 8, as the Cr content increases, the Curie temperature Tc of the alloy decreases to 1310, 131
゜.

It can be seen that the value also decreases. In order for Tc to be within the range of 42-90°C, the Cr content in this system must be 11.5
~13.7 at%.

Comparison of temperature rise characteristics with the powder of Example 3, Sample No. 1, which had the same particle size as the powder coated with polymer, was coated with silver as a non-magnetic metal, and was further coated with polymer. The result is shown in Figure 9. It can be seen that the heating characteristics are significantly improved by coating the non-magnetic metal with the polymer.

[Effects of the Invention] As detailed above, the extreme temperature amorphous alloy of the present invention has a Curie temperature as low as 42 to 90°C due to an increase in the amount of Ni added. See you again! By adding , the Curie temperature can be lowered even if the amount of Ni added is suppressed,
At the same time, a decrease in saturation magnetic flux density can be avoided. In general, by coating the surface of the temperature-sensitive amorphous alloy with a non-magnetic metal, the time required to raise the temperature to the treatment temperature can be shortened. Such an amorphous alloy of the present invention will not be heated above a predetermined temperature correlated with the Curie temperature even if the external magnetic field is increased. Therefore, the temperature of the affected area, such as cancer, can always be set at a desired level without requiring special control, and is effective in induction heating therapy such as cancer treatment. Furthermore, by coating the surface of the temperature-sensitive amorphous alloy with a polymer resin that is harmless to living organisms, it is possible to prevent the outflow of metal ions that are harmful to living organisms, thereby ensuring the safety of living organisms.

Furthermore, the temperature-sensitive amorphous alloy of the present invention has Cr and/or
Or, it has a Curie point as low as 42 to 90°C due to the addition of Mo. Furthermore, by coating the surface with a non-magnetic metal, the heating rate can be increased and the heat generation efficiency can be increased. Such an amorphous alloy of the present invention will not be heated above a predetermined temperature correlated with the Curie temperature even if the external magnetic field is increased.

Therefore, the temperature of the affected area, such as cancer, can always be set at a desired level without requiring special control, and is effective in induction heating therapy such as cancer treatment. Furthermore, by coating the surface of the temperature-sensitive amorphous alloy with a polymer resin that is harmless to living organisms, it is possible to prevent the outflow of metal ions that are harmful to living organisms, thereby ensuring safety.

[Brief explanation of the drawing]

FIG. 1 is a schematic diagram showing an apparatus for measuring the temperature rise characteristics and magnetic properties of the temperature-sensitive amorphous alloy powder of the present invention, and FIGS. 2 and 6 show the particle size of the temperature-sensitive amorphous alloy powder. FIG. 3 is a graph showing the particle size and temperature rising characteristics of a temperature-sensitive amorphous alloy powder coated with a non-magnetic metal, and FIG. 4 is a graph showing the relationship between FIG. 5 is a graph showing the relationship between temperature-sensitive amorphous alloy powder and inductance.
FIG. 7 is a graph showing the relationship between Cr content and Curie temperature; FIG. 7 is a graph showing the temperature rise characteristics of polymer-coated and non-polymer coated materials; FIG. 8 is a graph showing the relationship between Cr content and Curie temperature. FIG. 7 is a graph, and FIG. 9 is a graph showing the temperature increase characteristics of a temperature-sensitive amorphous alloy coated with a polymer and a temperature-sensitive amorphous alloy coated with a noble metal and further coated with a polymer.

Claims (3)

[Claims] (1) Contains one or more transition metals of Fe, Ni, and Co and one or more metalloids of P, C, Si, and B, and has a Curie temperature of 42°C to 90°C 1. A temperature-sensitive amorphous alloy for thermotherapy, characterized in that the surface of the alloy is coated with a polymer resin that is harmless to living organisms. (2) The temperature-sensitive amorphous alloy for thermotherapy according to claim 1, characterized in that a small amount of Al is added thereto. (3) The temperature-sensitive amorphous alloy for thermotherapy according to claim 1, which contains Cr and/or Mo.