JPH05228219A - Cancer treating thermo-element composition - Google Patents

Abstract

PURPOSE:To provide a cancer treating thermo-element composition capable of artificially controlling the local administration of an anticancer drug, being inserted with a catheter or a retention needle, and concurrently applying the cancer chemotherapy and thermotherapy requiring no electromagnetic wave output adjustment and no temperature measurement. CONSTITUTION:A cancer treating thermo-element composition is covered with a conducting metal film 2 of 0.5-3mum on the surface of magnetic powder having the curie temperature of 42-90 deg.C, an anti-cancer drug 3 is coated or stuck on it, and a thermosensitive macromolecule 4 meltable at 40-70 deg.C is coated on it.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a thermal element composition for treating cancer, and more specifically, it is a magnetic induction method in hyperthermia (hyperthermia), which is one of the methods for treating malignant tumors such as cancer, and locally heats it. The present invention relates to a thermal element composition for cancer treatment, which can be used as an implant material for cancer and can be used in combination with cancer chemotherapy by releasing an anticancer agent.

[0002]

2. Description of the Related Art The usual method of drug administration in cancer chemotherapy is systemic administration by intravenous injection using a syringe. However, side effects due to toxicity of the drug to be administered have become a problem. That is, the anti-cancer agent has similar toxicity exertion values to tumor cells and normal cells regardless of their origin and action. Therefore, how to selectively concentrate the anti-cancer agent on the cancer cells and make it act for a long time is a problem.

As a method for solving the above problems, research on microcapsules and microspheres has been conducted. The microcapsule has a mechanism in which an anticancer agent is put in the capsule and the anticancer agent can be gradually released into the living body through the outer wall of the capsule. In addition, since the microcapsules themselves have no tumor tropism, chemoembolization therapy by selective injection into the tumor-dominant artery is mainly applied. However, the control of anticancer drug administration in microcapsules depends on the physical and physical properties of the outer wall constituents.
It has the drawback that it is easily determined by its chemical properties and structure, and that it cannot be controlled artificially.

Microspheres are particles in which an anticancer agent is dispersed in albumin microspheres used as a blood circulation system contrast agent. However, since albumin microspheres may swell or dissolve in an aqueous solution, the release behavior of the contained drug becomes complicated, and it is difficult to control artificial release.

As a mechanism for artificially releasing an anticancer agent by some method, a drug releasing element to which a magnetic material is applied has been disclosed in Utility Model No. 2-35750. This element is
Since it is a ferrite sintered body, an incision operation is required to implant it in the living body. Further, the drug release control is performed by the heat generation of the magnetic body by applying a magnetic field, but since it is a ferrite sintered body, the heat generation of the sintered body differs depending on the magnetic field application direction, so it is considered that actual release control is difficult.

[0006] In recent years, the therapeutic effect of cancer by the combined use of chemotherapy for cancer and hyperthermia has been revealed. As a reason for enhancing the lethal effect of cancer cells by the combined use, a compensatory effect due to the difference between the hypersensitive cancer cell cycle (cell age) by hyperthermia and the hypersensitive cancer cell cycle by anticancer agents, the prevention of cancer recurrence by heating when the anticancer agent effects decrease, and It can be mentioned that the cancer cell membrane permeability of the anticancer agent is increased by heating.

[0007] In general, local hyperthermia often uses electromagnetic waves. If the frequency is increased, local heating is possible but deep heating becomes difficult, and if the frequency is lowered, deep heating is facilitated. It has an essential problem of widening the heating range. If the temperature inside the living body is not measured and the measured temperature is not used for feedback control of the electromagnetic wave output, the temperature of the heated portion of the living body rises excessively, which may be harmful to the living body.

A method called soft heating method is being developed in recent years to cover the problems of hyperthermia applying these electromagnetic waves. 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 exciting with a high-frequency magnetic field is used as a heat source to heat. According to this method, since the treatment temperature is determined by the Curie temperature of the temperature sensitive element, it is not necessary to adjust the electromagnetic wave output.

[0009]

From the above, the problem to be solved by the present invention is to artificially control the local administration of an anticancer agent so that implantation in a living body does not damage the patient as much as possible. Can be injected with a catheter or indwelling needle,
Moreover, the local heating is performed by the soft heating method which does not require the adjustment of the electromagnetic wave output and the temperature measurement, and the combined treatment of the cancer chemotherapy and the hyperthermia is intended to be performed by one type of element.

Therefore, an object of the present invention is to provide a hyperthermia for cancer treatment which can be used as an implant material for local heating in the soft heating method in the magnetic induction system and can be used in combination with cancer chemotherapy by artificial release control of an anticancer agent. It is to provide an element.

[0011]

As a result of various studies for solving the above problems, as a result, a magnetic powder having a disk-like magnetic powder having a Curie temperature of 42 ° C. to 90 ° C. and a powder shape of 0.5 to 3 is formed.
A conductive metal film is coated to a thickness of μm, an anticancer agent is coated or adhered on it, and a temperature-sensitive polymer is further coated thereon to prepare a temperature-sensitive magnetic powder.
When a high frequency alternating magnetic field of 00KHz · 3400A / m is applied, the temperature-sensitive magnetic powder is heated, the temperature-sensitive polymer film is melted, and the release of the anticancer drug can be artificially controlled. After melting and dispersing the anticancer agent, it was confirmed that hyperthermia can be performed by the residual temperature-sensitive magnetic material, and the present invention was completed.

In the present invention, the Curie temperature of the temperature-sensitive magnetic powder must be in the range of 42 to 90 ° C. and above the melting point of the polymer film. Examples of magnetic materials having a Curie temperature in the range of 42 to 90 ° C. include temperature-sensitive amorphous alloys and Fe—Pt alloys described in JP-A-2-47243 and JP-A-2-61036. This is because if the Curie temperature is less than 42 ° C., it is not possible to heat the treatment temperature range effective as hyperthermia, and if it exceeds 90 ° C., the treatment temperature range of hyperthermia is exceeded and overheating occurs. The preferred Curie temperature range is 45-55 ° C. The device of the present invention can be specifically injected into a living body by a catheter or the like by setting the device particle size to 100 μm or less. Further, the temperature-sensitive magnetic material must be disk-shaped and have an aspect ratio of diameter to thickness of 3 to 10. When the aspect ratio is 3 or the diameter is 30 μm or less, the magnetic flux is not sufficiently focused and heat is not generated. If the aspect ratio exceeds 10 or the diameter exceeds 100 μm, the fluidity of the powder becomes extremely poor, and injection becomes difficult. A preferable range is an aspect ratio of 5 to 8 and a diameter of 40 to 60 μm.

The conductive metal coating the magnetic material must have a coating thickness of 0.5 to 3 μm. When the thickness is 0.5 μm or less, the resistance of the conductive metal is too high and eddy current does not occur.
On the other hand, if it exceeds 3 μm, the temperature cannot be controlled by the magnetic material. The preferred range is 1-2 μm.

The anticancer agent need not be coated on the entire surface of the temperature-sensitive magnetic powder, but may be a scattered coating. The anticancer agent can be coated by determining the required addition amount from the amount of the element of the present invention to be injected. The coating method includes chemical, physicochemical, and physical methods. As a simple method, the surface of the magnetic substance can be coated with the anticancer agent by mechanical granulation.

When the temperature-sensitive polymer film has a melting point of 40 ° C. or lower, it may melt when injected into a living body without applying a high frequency magnetic field, and is 70 ° C. or higher. Since the polymer film does not melt sufficiently even when the temperature-sensitive magnetic powder generates heat, the temperature-sensitive polymer film needs to be melted at 40 to 70 ° C. A preferable melting temperature range is 42 to 50 ° C.
As a polymer having a melting temperature in this range, a wax contained in a suppository, a polymer of polyacrylic amide and butyl methacrylate, or a complex of a low-melting polymer harmless to the living body is considered.

[0016]

EXAMPLE A device composition of the present invention in which an oxide magnetic powder having a Curie temperature of 50 ° C. is coated with a conductive metal film and an anticancer agent, and a suppository temperature-sensitive polymer composite which melts at 43 ° C. is further coated thereon. A schematic diagram of the product is shown in FIG. Reference numeral 1 is a disc-shaped temperature-sensitive magnetic powder, 2 is a conductive metal film, and 4 is a temperature-sensitive polymer. Although 3 is an anticancer agent, it is not necessary to cover the entire surface of the magnetic powder. Further, FIG. 2 shows that the temperature-sensitive polymer film is 2
The polymer film that is heavily (three or more layers can be coated) has a high melting temperature close to that of the magnetic powder, and the melting temperature becomes lower toward the outside. With this, when the magnetic powder generates heat, it is selectively melted from the outer polymer film, and the drug release can be controlled by artificially applying an alternating magnetic field. Further, in FIG. 3, after the polymer film was melted and dispersed, the frequency was 200 KHz and the magnetic field strength was 340 in physiological saline.
It is a temperature rise characteristic when a high frequency magnetic field of 0 A / m is applied. Three
It can be seen that the treatment temperature of hyperthermia is reached within minutes.

The thermal element composition for cancer treatment of the present invention can be injected with a syringe or the like without being placed in a living body without performing an incision operation.

[0018]

EFFECTS OF THE INVENTION By using the thermogenic composition for treating cancer according to the present invention, it is possible to artificially and effectively control the release of the anticancer drug to the cancer cells, and further, to suppress the self-retention of the residual magnetic powder after the release of the anticancer drug. Heat treatment with temperature control is possible.

[Brief description of drawings]

FIG. 1 is a schematic view showing an example of a thermal element composition for treating cancer according to the present invention.

FIG. 2 is a schematic view showing another example of the thermal element composition for cancer treatment according to the present invention.

FIG. 3 is a graph showing temperature rising characteristics when a high frequency magnetic field is applied to the heating element composition according to the present invention.

[Explanation of symbols]

 1 Oxide magnetic material 2 Conductive metal film 3 Anticancer agent 4 Thermosensitive polymer

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Sakae Minagawa 4-14-1, Suehiro, Kumagaya-shi, Saitama Stock company Riken Kumagaya Works

Claims (4)

[Claims] 1. A part or all of the surface of the oxide magnetic material having a Curie temperature of 42 ° C. to 90 ° C. is 0.5 to 3 μm.
A thermal treatment element for cancer characterized by being coated with a conductive metal film of m, coated with or adhered with an anticancer agent, and further coated with a temperature-sensitive polymer that melts at 40 ° C to 70 ° C. Composition. 2. The oxide magnetic material has an aspect ratio of thickness and diameter (diameter / thickness) of 3 to 10, and a diameter range of 30 to.
The thermal element composition for treating cancer according to claim 1, which has a disk shape of 100 μm. 3. The thermal element composition for cancer treatment according to claim 1, wherein the conductive metal film has a thickness of 1 μm −2 μm. 4. The thermal element composition for cancer treatment according to claim 1, wherein the temperature-sensitive polymer has a melting temperature range of 42 ° C. to 50 ° C.