JP7570629B2 - Radiation Therapy Bolus Material - Google Patents

Description

The present invention relates to a bolus material used in radiation therapy.

When irradiating the human body with radiation to treat cancerous tissues inside the body, it is desirable to concentrate the radiation on the affected area and avoid exposing healthy tissues other than the affected area to radiation as much as possible.

Therefore, as shown in Patent Documents 1 to 3, a resin material called a bolus material is attached to the surface of the human body to adjust the position of the peak point of the radiation energy to match the depth of the affected area. Patent Document 1 discloses a bolus material made of an aqueous gel, Patent Document 2 discloses a polyurethane-based bolus material, and Patent Document 3 discloses a silicone rubber-based bolus material.

In addition to characteristics such as having a specific gravity close to that of the human body, not impeding the permeability of radiation, and being transparent, radiation therapy bolus materials are also required to be flexible and adhere easily to the human body. However, flexible soft materials have low strength, making them difficult to reuse. In addition, radiation therapy bolus materials are often used in sheet form, cut according to the shape of the radiation site, but the remaining parts of the cut sheets are usually discarded.

Japanese Unexamined Patent Publication No. 62-204770 JP 2018-76478 A Japanese Patent Application Publication No. 11-221294

The object of the present invention is therefore to solve the above-mentioned problems and provide a reusable bolus material for radiation therapy.

The bolus material for radiotherapy of the present invention, which has been made to solve the above problems, is a bolus material for radiotherapy made of a self-repairing polymer containing a highly hydrophilic solvent in a crosslinked structure in which a host group and a guest group are crosslinked by interaction, and is characterized in that the cut pieces are rejoined to be tightly integrated to form a bolus material for radiotherapy having a larger volume than the cut pieces . Also, the method for using the bolus material for radiotherapy is to contact at least two or more sheets of the bolus material for radiotherapy with each other to tightly integrate them to form a bolus material for radiotherapy having a larger volume than the original bolus material for radiotherapy.

In addition, a bolus material for radiation therapy, which is characterized by being composed of a self-repairing polymer containing a highly hydrophilic solvent in a crosslinked structure in which a host group and a guest group are crosslinked by interaction , can be structured by laminating a styrene-based thermoplastic elastomer having polystyrene as a hard segment and polyethylene/polybutylene as a soft segment.

Radiation therapy bolus materials are often used in sheet form, cut to fit the shape of the human body surface at the radiation site, but the radiation therapy bolus material of the present invention is made of a self-repairing polymer and has self-repairing properties, so if the cut pieces are overlapped, they will rejoin and become one piece. This allows for repeated use. Furthermore, this type of self-repairing polymer loses its self-repairing properties when it dries, but by laminating it with a sheet of soft, water-impermeable thermoplastic elastomer, it is possible to prevent drying without impairing its function as a bolus material. This allows for reuse for a longer period of time.

FIG. 2 is a diagram illustrating the principle of the bolus material. FIG. 1 is a diagram illustrating the principle of a self-repairing polymer. FIG. 11 is a cross-sectional view showing an embodiment having a laminated structure. FIG. 11 is a cross-sectional view showing another embodiment of a laminate structure.

Figure 1 shows the principle of the bolus material for radiation therapy.
For example, when the depth from the surface 10 of the human body to the affected tissue 11 is d, if radiation is applied as shown in Fig. 1(A), the position of the peak point P of the radiation dose will be Δd lower than d as shown in the graph on the right, and the radiation dose may not be maximum in the affected tissue 11. In such a case, as shown in Fig. 1(B), if a bolus material 12 for radiotherapy with a thickness Δd and radiation permeability equivalent to that of the human body is brought into close contact with the surface 10 of the human body, the position of the peak point P with the maximum dose will shift upward by Δd, and the radiation dose can be maximized in the affected tissue 11.

The bolus material for radiation therapy of the present invention is described below.

The bolus material for radiotherapy of the present invention is made of a self-healing polymer that contains a highly hydrophilic solvent in a cross-linked structure in which a host group and a guest group are cross-linked by interaction. As conceptually shown in Figure 2, this self-healing polymer is a cross-linked structure in which a host group having a host molecule 20 in its side chain is cross-linked with a guest molecule group having a guest molecule 21 in its side chain. This self-healing polymer itself is sold as a self-healing gel by Yushiro Chemical Industry Co., Ltd., and an overview of it is provided below.

The host molecule 20 is, for example, cyclodextrin. Cyclodextrin is a cyclic oligosaccharide with a donut-shaped molecular structure, and has the property of encapsulating a guest molecule 21 of a suitable size inside this ring. Known types of cyclodextrin include α-cyclodextrin, which has six glucose residues, β-cyclodextrin, which has seven glucose residues, and γ-cyclodextrin, which has eight glucose residues, and any of these can be used.

The guest molecule 21 is a chain or cyclic alkyl compound having 4 to 18 carbon atoms and its derivatives. Examples of alkyl compounds having 4 to 18 carbon atoms include butane, pentane, hexane, heptane, octane, nonane, decane, undecane, dodecane, tetradecane, pentadecane, hexadecane, octadecane, adamantane, etc.

Bonds are formed between these host molecules 20 and guest molecules 21 through interaction, and a cross-linked structure is formed using these bonds as cross-linking points. Examples of such interactions include hydrophobic interactions, hydrogen bonds, intermolecular forces, electrostatic interactions, and coordinate bonds between the host molecules 20 and the guest molecules 21, but are not limited to these.

The most preferred combinations of host molecule 20 and guest molecule 21 are α-cyclodextrin and n-dodecyl group, and β-cyclodextrin and adamantyl group. This is because the closer the size of guest molecule 21 and the size of the internal cavity of host molecule 20 are, the stronger the inclusion force becomes.

Examples of monomers having a host molecule in their molecular structure include 6-(meth)acrylamide-α-cyclodextrin, 6-(meth)acrylamide-β-cyclodextrin, α-cyclodextrin methacrylate, β-cyclodextrin methacrylate, α-cyclodextrin acrylate, β-cyclodextrin acrylate, etc.

Examples of monomers that have a guest molecule in their molecular structure include n-butyl (meth)acrylate, t-butyl (meth)acrylate, 1-acrylamidodamantane, N-(1-adamantyl)(meth)acrylamide, N-benzyl(meth)acrylamide, and N-1-naphthylmethyl(meth)acrylamide.

The crosslinked structure described above contains a highly hydrophilic solvent. This is because the self-repairing polymer dries up when the water evaporates, and the self-repairing function that occurs in the hydrogel state decreases. Examples of this highly hydrophilic solvent include ethylene glycol, diethylene glycol, propylene glycol, dipropylene glycol, polyethylene glycol, polypropylene glycol, glycerin, and diethylene glycol monoethyl ether. This makes it less likely to dry out even over time or when the temperature environment changes, so it is possible to maintain a stable self-repairing function for a long period of time.

Such a self-repairing polymer can be produced by mixing a monomer having a host molecule in its molecular structure, a monomer having a guest molecule in its molecular structure, a monomer not containing a host molecule or a guest molecule, a highly hydrophilic solvent as an anti-drying liquid, and a polymerization initiator, and polymerizing them at room temperature. The monomers can be mixed together to form an aqueous monomer solution. The amount of the aqueous monomer solution added is preferably 30% to 70% by weight. The amount of the anti-drying agent added is preferably 20% to 40%. Furthermore, the amount of the polymerization initiator is preferably 1% to 10%.

Polymerization initiators include, but are not limited to, ammonium persulfate, azobisisobutylnitrile, 2,2'-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride, etc., and various polymerization initiators such as benzoyl peroxide and photopolymerization initiators can be used.

This self-repairing polymer contains host molecules 20 and guest molecules 21 inside, and even if it is cut, the host molecules 20 exposed at the interface encapsulate the guest molecules 21, forming crosslinks again and repairing the cut surface. This self-repairing function occurs in a swollen state, and its function decreases in a dry state, but by including a highly hydrophilic solvent, a stable self-repairing function can be obtained. It has been confirmed that the gel strength of the self-repaired portion after cutting reaches 85% of that before cutting.

The bolus material for radiotherapy of the present invention is made of the above-mentioned self-repairing polymer, and is often formed into a sheet for use. For example, by varying the thickness of the sheets in 1 mm increments and stacking the required number of sheets according to the depth of the affected area, they will adhere to each other and can be used as a bolus material for radiotherapy of the required thickness. Even if the sheet is cut according to the condition of the affected area, if the cut pieces are collected, they can be adhered to each other and integrated, and can be reused. Therefore, there is no waste as with conventional bolus materials for radiotherapy.

As described above, the self-repairing polymer can be used alone as a bolus material for radiation therapy, but it can also be used by laminating a sheet 22 of the self-repairing polymer and a sheet 23 of a styrene-based thermoplastic elastomer as shown in Figure 3. Figure 3 shows a bolus material for radiation therapy in which these two types of sheets 22, 23 are alternately laminated.

As a styrene-based thermoplastic elastomer with polystyrene as the hard segment, one that is soft, impermeable, and has a specific gravity of less than 1 is preferred, and in this embodiment, a thermoplastic elastomer with polystyrene as the hard segment and polyethylene/polybutylene as the soft segment is used. This is a material called SEBS (styrene-ethylene-butylene-styrene), which is obtained by hydrogenating a polystyrene-polybutadiene-polystyrene block copolymer.

Other styrene-based block-type thermoplastic elastomers having polystyrene as a hard segment include styrene-ethylene block copolymers, styrene-ethylene-butadiene block copolymers, styrene-butadiene block copolymers, styrene-butadiene block copolymers, and styrene-isoprene block copolymers. From the viewpoints of easily deforming to conform to the irregularities of the human body, easily fitting appropriately to the human body, and being strong and resistant to damage, SEBS (styrene-ethylene-butylene-styrene) obtained by hydrogenating a polystyrene-polybutadiene-polystyrene block copolymer is preferred.

This styrene-based thermoplastic elastomer has excellent rubber elasticity close to that of cross-linked rubber at room temperature, making it easy to adhere to the contours of the human body. Moreover, when heated to 140-230°C, it exhibits fluidity and can be molded in the same way as ordinary resins. It also has excellent transparency, and has a tensile strength of 1.3 MPa according to the JIS K 6251 testing method, which is sufficient strength. This styrene-based thermoplastic elastomer material itself is an existing product, and is commercially available, for example, from Aronkasei Co., Ltd.

From the viewpoint of radiation permeability, it is preferable that the specific gravity of the radiation therapy bolus material is as close as possible to the specific gravity of the human body (1.0). The specific gravity of the above self-healing polymer is 1.25, which is slightly above the preferred range. In contrast, the specific gravity of the above styrene-based thermoplastic elastomer is 0.86. Therefore, by alternately laminating the materials, the overall specific gravity can be brought closer to 1.0, making it possible to prevent deterioration of radiation permeability due to the difference in specific gravity with the human body. In addition, since styrene-based thermoplastic elastomers are not permeable to water, laminating them with self-healing polymers has the effect of reliably preventing the self-healing polymer from drying out.

In addition, as shown in FIG. 4, if a laminate structure is formed in which thermoplastic elastomer sheets 23 are placed on both the top and bottom of the self-repairing polymer sheet 22, the self-repairing polymer can be more reliably prevented from drying out.

60% by weight of monomer aqueous solution, available from Yushiro Chemical Industry Co., Ltd. under the trade name "Wizard Monomer", was mixed with 35% by weight of drying prevention liquid, and 5% by weight of polymerization initiator aqueous solution was added and stirred, then poured into a mold to form a sheet. The monomer aqueous solution was a mixture of a host group-containing polymerizable polymer, a guest group-containing polymerizable monomer, and a polymerizable monomer. The host group-containing polymerizable polymer was acrylamide-cyclodextrin, the guest group-containing polymerizable monomer was N-(1-adamantyl)acrylamide, and the polymerizable monomer was 4-hydroxybutyl acrylate. The drying prevention liquid was a water-soluble alcohol, and the polymerization initiator was ammonium persulfate. It hardened in about 20 minutes at room temperature and was peeled off from the mold to form a sheet-shaped bolus material for radiation therapy. Its specific gravity was 1.25, and it had excellent adhesion and transparency. The cut pieces of the sheet were collected and left in the air at room temperature, and fused together and integrated within 24 hours.

Next, a sheet was made from styrene-based thermoplastic elastomer pellets (SEBS) sold by Aronkasei Co., Ltd. The sheet was made by molding the pellet-shaped resin with a roll heated to 150°C to 190°C. The sheets made were layered alternately with sheets of self-repairing resin to create a bolus material for radiation therapy consisting of a total of six sheets. The overall specific gravity was 1.0, and it also had excellent adhesion and transparency. There are many possible configurations for the layering, such as varying the thickness of each layer.

As explained above, the bolus material for radiation therapy of the present invention has self-repairing properties and can be used repeatedly. Furthermore, by laminating it with a sheet of soft, water-impermeable thermoplastic elastomer, drying is prevented, making it possible to reuse it for a longer period of time.

10: human body surface 11: diseased tissue 12: bolus material for radiation therapy 20: host molecule 21: guest molecule 22: self-repairing polymer sheet 23: thermoplastic elastomer sheet
P Peak radiation dose

Claims (3)

A bolus material for radiation therapy comprising a self-repairing polymer containing a highly hydrophilic solvent in a crosslinked structure in which a host group and a guest group are crosslinked by interaction, characterized in that the cut pieces can be rejoined to form a bolus material for radiation therapy having a larger volume than the cut pieces by tightly bonding the cut pieces together . A method for using a bolus material for radiotherapy, comprising contacting at least two or more sheets of the bolus material for radiotherapy described in claim 1 with each other to form a bolus material for radiotherapy having a larger volume than the original bolus material for radiotherapy. A bolus material for radiation therapy, characterized in that it is made of a self-repairing polymer containing a highly hydrophilic solvent in a crosslinked structure in which a host group and a guest group are crosslinked by interaction, and is laminated with a styrene-based thermoplastic elastomer having polystyrene as a hard segment.

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