JP6651976B2 - Liquid material for bolus formation, bolus, and method of manufacturing the same - Google Patents

Description

  The present invention relates to a liquid material for forming a bolus, a bolus, and a method for manufacturing the bolus.

  2. Description of the Related Art Irradiation of human body with radiation or laser beam such as X-ray, γ-ray, electron beam, neutron beam, α-ray and the like is widely used for treating diseases such as cancer. In general, when a material is irradiated with radiation, the amount of the original radiation decreases exponentially as it goes deeper, but the scattered radiation increases relatively deeper and its direction varies.

In particular, in the case of high-energy radiation, since the direction of the recoil electrons (scattered rays) is mainly ahead, scattering to the side is reduced, and the dose at a certain depth than the surface dose is maximized. If treatment is performed without considering the nature of such radiation in the skin, harmful effects of unnecessary radiation irradiation may be exerted on normal tissues other than the target (affected part).
In order to prevent this, a bolus is used to fill an irregular surface of the human body or the like, or to fill a missing part, and irradiates only a target using a substance equivalent to human body tissue. There is a way to do that.
Here, the substance equivalent to the human body tissue means a substance having substantially the same properties as radiation absorption or scattering as the human body tissue.

  In general, a bolus worthy of practical use is (1) a substance equivalent to human tissue, (2) a homogeneous substance, (3) excellent in plasticity, has appropriate elasticity, and is suitable for living organisms. (4) No toxicity, (5) No change in energy, (6) Uniform thickness, (7) No air mixing, ( It is necessary to satisfy characteristics and functions such as 8) high transparency and (9) easy disinfection.

Until now, bolus materials include, for example, plastics, paraffins, synthetic rubbers, silicones, gum bases, agar, acetoacetylated aqueous polymer compounds (for example, see Patent Document 1), and specific polyvinyl alcohols that are frozen or thawed. Non-fluid gels (for example, see Patent Literature 2), specific hydrogels of natural organic polymers (for example, see Patent Literature 3), and transparent silicone gels (for example, see Patent Literature 4) produced by repeating the operation. Proposed.
Patent Literature 5 proposes a bolus for radiation therapy. This is a bolus for radiation therapy such as a particle beam, which is used in a method of irradiating an affected part of a patient with radiation from two directions to treat the affected part. As shown in FIG. 5 of Patent Document 5, two boluses are combined to control the irradiation shape of radiation in order to conform to the shape of a lesion in the body, and are used for treatment.

  SUMMARY OF THE INVENTION It is an object of the present invention to provide a bolus that can adhere to a patient's skin surface without any gap and has an appropriate radiation transmittance distribution corresponding to an affected part of the patient.

The bolus of the present invention as a means for solving the above-mentioned problem is a bolus for applying to a patient who receives radiation treatment,
It has a shape along the body surface to be irradiated with radiation of the patient and a radiation transmittance distribution corresponding to the affected part of the patient.

  According to the present invention, it is possible to provide a bolus that can adhere to the skin surface of a patient without any gap and has an appropriate radiation transmittance distribution corresponding to the affected part of the patient.

FIG. 1 is a conceptual diagram of irradiating an affected part of a patient with X-rays using a bolus. FIG. 2 is a diagram in a case where X-rays are irradiated using a uniform bolus. FIG. 3 is a diagram in the case where X-rays are irradiated using a bolus having a composition distribution. FIG. 4 is a conceptual diagram showing a bolus having a composition distribution as viewed from above and a transmitted light amount of X-rays. FIG. 5 is a conceptual diagram in which the shape of the bolus is changed. FIG. 6 is a schematic diagram showing an example of a water-swellable layered clay mineral as a mineral and a state in which the water-swellable layered clay mineral is dispersed in water. FIG. 7 is a schematic diagram of a male bolus for a breast produced by a three-dimensional printer. FIG. 8 is a schematic diagram of a female bolus for a breast produced by a three-dimensional printer. FIG. 9 is a schematic diagram combining a breast bolus produced by a three-dimensional printer. FIG. 10 is a schematic diagram of a bolus taken out of the mold. FIG. 11 is a schematic diagram of a three-dimensional printer for producing a bolus. FIG. 12 is a schematic diagram in which a bolus produced by a three-dimensional printer is peeled from a support material. FIG. 13 is a schematic diagram of a three-dimensional printer having another configuration for producing a bolus.

(Bolus)
The bolus of the present invention is a bolus for application to a patient undergoing radiation therapy,
It has a shape along the body surface to be irradiated with radiation of the patient and a radiation transmittance distribution corresponding to the affected part of the patient.

The bolus of the present invention is a conventional bolus having a flat plate shape manufactured using a mold, so that it is difficult to completely adhere to a patient's skin surface without any gap, and in such a method. Since the bolus itself does not change in the composition of the whole bulk and has one characteristic, the transmittance of radiation is controlled only by the thickness of the bolus. It is based on
Further, in the technique described in Patent Document 5, two boluses are used in combination, the compositions of these boluses are uniform, and the transmittance of the radiation is not controlled. It only filters out opacity. On the other hand, in the present invention, a single bolus is used to provide a radiation transmittance distribution by controlling the composition and shape, and the radiation dose distribution of the radiation passing therethrough is controlled. For this reason, the two are essentially different.

<Shape along the body surface to be irradiated by the patient>
The bolus produced in the present invention has a shape along the body surface to be irradiated with radiation of the patient, using the patient's personal data. As a result, a bolus that fits perfectly on the patient's skin can be formed.
Here, having a shape along the body surface, on the body surface to be subjected to radiation irradiation of the individual patient, a certain shape such as a convex portion or a concave portion with respect to the concave or convex portion of the body, respectively. It means holding.

<Transmission distribution of radiation corresponding to affected part of patient>
The bolus produced in the present invention has an appropriate radiation transmittance distribution corresponding to the affected area of the individual patient. This makes it possible to reduce adverse effects on other than cancer cells.
Here, an advantage in the case of having a radiation transmittance distribution will be described. For example, in the case of treatment by X-ray irradiation, there are the following disadvantages.
-The body surface other than cancer cells is affected by more radiation than cancer cells, and cells behind cancer cells are also affected.
・ The shape cannot be processed.
-When a disorder such as the heart or lungs occurs, it is necessary to avoid deadly organs and irradiate.

Here, FIG. 1 shows a state of irradiating the affected part 32 of the patient with X-rays. A bolus 30 is placed on the skin surface 31 of the affected part 32, and X-rays are emitted from the surface.
As shown in FIG. 2, when the conventional bolus 33 is used, since the composition of the bolus 33 is uniform, the irradiation depth of the X-ray can be controlled, but the bolus 33 is controlled uniformly. For this reason, only the peak of the incident X-rays is uniformly controlled in the depth direction and the surrounding area. This is the point that the aforementioned shape cannot be processed. For this reason, cells other than cancer cells and the body surface are strongly affected by radiation (X-rays). Reference numeral 34 in FIG. 2 indicates an X-ray (homogeneous) transmitted through the bolus.
On the other hand, FIG. 3 shows a case where an X-ray transmittance distribution is given. In this case, the composition of the bolus 35 is changed to provide a composition distribution. This makes it possible to change the X-ray transmittance and provide an X-ray transmittance distribution. FIG. 3 shows a state where the thickness is constant and only the composition is changed, but the film thickness can also be changed at the same time, and by combining the two, it becomes possible to irradiate cancer cells with focused X-rays. . This makes it possible to reduce adverse effects on other than cancer cells. Reference numeral 36 in FIG. 3 indicates an X-ray (having a distribution) transmitted through the bolus.
As shown below, there are two ways to form the X-ray transmittance distribution, a case where a bolus composition distribution is provided, and a case where the composition is controlled by the shape, or a combination of both.

-Composition distribution-
As described above, in order to form the bolus of the X-ray transmittance distribution, there is a method of giving a composition distribution constituting the bolus.
FIG. 4 is a diagram showing a state in which a bolus 35 with a composition distribution is viewed from above and a transmission amount distribution of X-rays. The black portion of the bolus has a composition with a high rate of attenuating X-rays, and the white portion has a high rate of transmission. X-rays that have passed through such a bolus have a high intensity at the center and can be focused and irradiated on cancer cells and the like.
The composition distribution can be formed, for example, by using an ink-jet type three-dimensional printer and using a plurality of bolus forming liquid materials. In particular, the relationship between the composition (moisture content) and the X-ray transmittance of the hydrogel used in the present invention is uniquely determined, and the transmittance can be easily controlled.

−Shape control−
There is also a shape control method for giving an X-ray transmittance distribution.
For example, by making the shape as shown in FIG. 5, it becomes possible to reduce the irradiation amount to the peripheral part of the cancer cell.
Thus, the bolus composition distribution, the arbitrary control of the film thickness, and the combination of both cannot be achieved by the conventional method (molding). It is a molding method using a three-dimensional printer that can produce such epoch-making means, which is an important point of the present invention.

The bolus of the present invention is made of a hydrogel, and the hydrogel contains water, a polymer, and a mineral, preferably contains an organic solvent, and more preferably contains other components as necessary.
The bolus is formed by cross-linking the mineral dispersed in an organic solvent and the polymer obtained by polymerizing the polymerizable monomer, and forming a complex in a three-dimensional network structure, wherein the solvent is included in the hydrogel. It preferably comprises a gel.
The bolus is manufactured using a bolus-forming liquid material containing water, a mineral, and a polymerizable monomer, which will be described later.

-Polymer-
Examples of the polymer include a polymer having an amide group, an amino group, a hydroxyl group, a tetramethylammonium group, a silanol group, an epoxy group, and the like, and are preferably water-soluble.
The polymer may be a homopolymer (homopolymer) or a heteropolymer (copolymer), may be modified, or may have a known functional group. Or a salt form, but a homopolymer is preferred.
In the present invention, the water solubility of the polymer means that, for example, when 1 g of the polymer is mixed with 100 g of water at 30 ° C. and stirred, 90% by mass or more thereof is dissolved.

  The polymer is obtained by polymerizing a polymerizable monomer. The polymerizable monomer will be described in a bolus forming liquid material described later.

−Water−
As the water, for example, pure water such as ion exchange water, ultrafiltration water, reverse osmosis water, and distilled water, or ultrapure water can be used.
Other components such as an organic solvent may be dissolved or dispersed in the water according to the purpose of imparting moisture retention, imparting antibacterial properties, imparting conductivity, adjusting hardness, and the like.

-Mineral-
The mineral is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include a water-swellable layered clay mineral.
The water-swellable layered clay mineral has a state in which two-dimensional disc-shaped crystals having a unit cell in the crystal are stacked as shown in the upper diagram of FIG. 6 dispersed in water in a single layer state, When the water-swellable lamellar clay mineral is dispersed in water, as shown in the lower diagram of FIG.

Examples of the water-swellable layered clay mineral include water-swellable smectite and water-swellable mica. More specifically, water-swellable hectorite containing sodium as an interlayer ion, water-swellable montmorillonite, water-swellable saponite, water-swellable synthetic mica and the like can be mentioned. These may be used alone or in combination of two or more. Among these, water-swellable hectorite is preferable because a highly elastic bolus can be obtained.
The water-swellable hectorite may be appropriately synthesized or may be a commercially available product. Examples of the commercially available products include synthetic hectorite (Laponite XLG, manufactured by Rockwood), SWN (Coop Chemical Ltd.), and fluorinated hectorite SWF (Coop Chemical Ltd.). Among these, synthetic hectorite is preferred from the viewpoint of the elastic modulus of the bolus.
The water swelling means that water molecules are inserted between layers of the layered clay mineral and dispersed in water as shown in FIG.

  The content of the mineral is preferably 1% by mass or more and 40% by mass or less, more preferably 1% by mass or more and 25% by mass or less with respect to the total amount of the bolus from the viewpoint of the elastic modulus and hardness of the bolus.

-Organic solvent-
The organic solvent is included to enhance the bolus' moisture retention.
Examples of the organic solvent include alkyl alcohols having 1 to 4 carbon atoms such as methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, sec-butyl alcohol, and tert-butyl alcohol; dimethylformamide And ketone alcohols such as acetone, methyl ethyl ketone and diacetone alcohol; ethers such as tetrahydrofuran and dioxane; ethylene glycol, propylene glycol, 1,2-propanediol and 1,2-butanediol. , 1,3-butanediol, 1,4-butanediol, diethylene glycol, triethylene glycol, 1,2,6-hexanetriol, thioglycol, hexylene glycol Polyalkylene glycols such as polyethylene glycol and polypropylene glycol; polyhydric alcohols such as ethylene glycol monomethyl (or ethyl) ether, diethylene glycol methyl (or ethyl) ether, and triethylene glycol monomethyl (or ethyl) ether. Lower alcohol ethers of polyhydric alcohols; alkanolamines such as monoethanolamine, diethanolamine, and triethanolamine; N-methyl-2-pyrrolidone, 2-pyrrolidone, 1,3-dimethyl-2-imidazolidinone, and the like. . These may be used alone or in combination of two or more. Among these, polyhydric alcohols are preferred from the viewpoint of moisture retention, and glycerin and propylene glycol are more preferred.
The content of the organic solvent is preferably from 10% by mass to 50% by mass with respect to the total amount of the bolus. When the content is 10% by mass or more, the effect of preventing drying is sufficiently obtained. When the content is 50% by mass or less, the layered clay mineral is uniformly dispersed.
When the content of the organic solvent is 10% by mass or more and 50% by mass or less, deviation from the composition of the human body is small, and a good function as a bolus can be obtained.

-Other components-
The other components are not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include a phosphonic acid compound such as 1-hydroxyethane-1,1-diphosphonic acid, a stabilizer, and a surface treatment agent. Examples include a polymerization initiator, a colorant, a viscosity modifier, an adhesion-imparting agent, an antioxidant, an antioxidant, a crosslinking accelerator, an ultraviolet absorber, a plasticizer, a preservative, and a dispersant.

-Coating-
It is effective to provide a coating on the surface of the bolus for the following three purposes.
(1) Maintain the bolus shape.
(2) Improve the preservability (drying resistance, antiseptic property) of the bolus.
(3) Improve the appearance of the bolus.

In order to maintain the shape of the bolus, it is preferable that the film has elasticity in order to prevent the bolus from collapsing due to its own weight. It is preferable that the difference in the Young's modulus of the bolus between the presence and absence of the film is 0.01 MPa or more.
The material for forming the film is not particularly limited and can be appropriately selected depending on the purpose. Examples thereof include polyester, polyolefin, polyethylene terephthalate, PPS, polypropylene, polyvinyl alcohol (PVA), polyethylene, polyvinyl chloride, and cellophane. , Acetate, polystyrene, polycarbonate, nylon, polyimide, fluororesin, paraffin wax and the like. These may be used alone or in combination of two or more. As a material for forming the film, a commercially available product can be used. Examples of the commercially available product include Plastic Coat # 100 (manufactured by Daikyo Chemical Co., Ltd.).
The film thickness of the film is not particularly limited and may be appropriately selected depending on the purpose. However, the film thickness is preferably 100 μm or less, more preferably 10 μm or more and 50 μm or less. When the film thickness is 100 μm or less, the texture of the hydrogel constituting the bolus can be maintained.

By forming a film on the surface of the bolus, the appearance of the bolus can be improved. For example, if the bolus has scratches or surface roughness on the surface, the appearance can be supplemented by a film. Moreover, the bolus inside can be protected by the film on the surface serving as a sacrificial layer.
In addition, since the surface of the bolus cannot be marked or the like, it is possible to write a procedure at the time of radiation treatment or a patient name by forming a film on the surface of the bolus. Properties can be imparted.

The method for forming the film is not particularly limited and may be appropriately selected depending on the purpose. Examples thereof include a method in which the material for forming the film is dissolved in a solvent and applied to the surface of a bolus. Examples of the coating method include brushing, spraying, and dip coating.
Further, there is a method in which a heat-shrinkable film is used as the film-forming material, and a laminate is formed on the surface of the hydrogel structure.
Alternatively, the film-forming material may be dissolved in a solvent, and the film may be formed at the same time when the bolus is formed by the three-dimensional printer using the bolus-forming liquid material.
In any case, since adhesion to the skin is important, it is possible to form a film that does not impair the bolus surface shape created based on the three-dimensional data of the body surface to be irradiated by the individual to be treated. It is important.

In order to improve the storage stability of the bolus, it is necessary to improve the drying resistance and the preservability.
In order to improve the drying resistance, it is effective to reduce the water vapor permeability and oxygen permeability of the film. Specifically, the water vapor permeability (JIS K7129) is preferably 500 g / m ² · d or less. Further, the oxygen permeability (JIS Z1702) is preferably 100,000 cc / m ² / hr / atm or less.
In order to improve the antiseptic property, the film preferably contains an antiseptic. The preservative is not particularly limited and can be appropriately selected depending on the intended purpose. For example, dehydroacetate, sorbate, benzoate, pentachlorophenol sodium, 2-pyridinethiol-1-oxide Sodium, 2,4-dimethyl-6-acetoxy-m-dioxane, 1,2-benzthiazolin-3-one and the like.

The shape, size, structure, and the like of the bolus are not particularly limited, and can be appropriately selected depending on the purpose.
The bolus is in the form of a flat plate. When the bolus is brought into close contact with the surface of the human body, it is used by pressing it against the skin or cut into a suitable size and connected.

In the bolus of the present invention, the CT value (HU) measured by computer tomography is in a range of −100 or more and 100 or less that can be actually used, preferably 0 or more and 100 or less, more preferably 0 or more and 70 or less. .
The CT value is a value calibrated by a computer tomography apparatus as bone 1,000, water 0, and air-1,000.
The bolus of the present invention is used for radiotherapy, and preferably has a composition close to the body composition.
Even if it says body composition, a CT value changes with parts. It is known that the muscle is about 35 to 50, the internal organ also varies depending on the site, the liver is about 45 to 75, and the pancreas is about 25 to 55.
Fat has a value of about -50 to -100, and blood has a value of about 10 to 30.
For this reason, if the CT value is generally -100 or more and 100 or less, a bolus exhibiting substantially the same properties as radiation absorption or scattering as human body tissue can be obtained, though it depends on the site to be irradiated. More preferably, it is 0 or more and 100 or less, and more preferably 0 or more and 70 or less, it can be said that the properties are very close.

Since the hydrogel used in the present invention is mainly composed of a polymer and water, it is close to the composition of the human body in the first place, and therefore the CT value is close to the value of the human body.
Furthermore, it is possible to arbitrarily change the composition ratio of the materials constituting the hydrogel (the ratio of the polymer or mineral to water and the mixing ratio of water and the organic solvent) to some extent. Along with this, the CT value can be changed, so that the CT value can be controlled to some extent according to the site to be subjected to radiation treatment.
As described above, a bolus made of a hydrogel has both physical properties and characteristics necessary for the bolus, and the hydrogel is one of the most excellent materials as a material of the bolus.

(Liquid material for bolus formation)
The liquid material for forming a bolus of the present invention preferably contains water, a mineral, and a polymerizable monomer, contains an organic solvent and a polymerization initiator, and further contains other components as necessary.
As the water, the mineral, the organic solvent, and the other components in the bolus-forming liquid material, those similar to the bolus can be used.

-Polymerizable monomer-
The polymerizable monomer is a compound having one or more unsaturated carbon-carbon bonds, and includes, for example, a monofunctional monomer and a polyfunctional monomer. Furthermore, examples of the polyfunctional monomer include a bifunctional monomer, a trifunctional monomer, and a tetrafunctional or higher monomer.

  The monofunctional monomer is a compound having one unsaturated carbon-carbon bond, for example, acrylamide, N-substituted acrylamide derivative, N, N-disubstituted acrylamide derivative, N-substituted methacrylamide derivative, N, N- Examples include disubstituted methacrylamide derivatives and other monofunctional monomers. These may be used alone or in combination of two or more.

  Examples of the N-substituted acrylamide derivative, N, N-disubstituted acrylamide derivative, N-substituted methacrylamide derivative, or N, N-disubstituted methacrylamide derivative include, for example, N, N-dimethylacrylamide (DMAA), N- Isopropylacrylamide and the like.

  Examples of the other monofunctional monomer include 2-ethylhexyl (meth) acrylate (EHA), 2-hydroxyethyl (meth) acrylate (HEA), 2-hydroxypropyl (meth) acrylate (HPA), and acryloyl morpholine (ACMO). ), Caprolactone-modified tetrahydrofurfuryl (meth) acrylate, isobornyl (meth) acrylate, 3-methoxybutyl (meth) acrylate, tetrahydrofurfuryl (meth) acrylate, lauryl (meth) acrylate, 2-phenoxyethyl (meth) acrylate, Isodecyl (meth) acrylate, isooctyl (meth) acrylate, tridecyl (meth) acrylate, caprolactone (meth) acrylate, ethoxylated nonylphenol (meth) acrylate Urethane (meth) acrylate. These may be used alone or in combination of two or more.

By polymerizing the monofunctional monomer, a water-soluble organic polymer having an amide group, an amino group, a hydroxyl group, a tetramethylammonium group, a silanol group, an epoxy group, and the like can be obtained.
The water-soluble organic polymer having an amide group, an amino group, a hydroxyl group, a tetramethylammonium group, a silanol group, an epoxy group, or the like is an advantageous component for maintaining the bolus strength.

  The content of the monofunctional monomer is not particularly limited and can be appropriately selected depending on the purpose. However, the content of the monofunctional monomer is preferably 1% by mass or more and 10% by mass or less based on the total amount of the bolus-forming liquid material. % Or more and 5% by mass or less. When the content is in the range of 1% by mass or more and 10% by mass or less, there is an advantage that the dispersion stability of the layered clay mineral in the liquid material for bolus formation is maintained and the stretchability of the bolus is improved. The extensibility refers to a property that the bolus is stretched and does not break when pulled.

  Examples of the bifunctional monomer include tripropylene glycol di (meth) acrylate, triethylene glycol di (meth) acrylate, tetraethylene glycol di (meth) acrylate, polypropylene glycol di (meth) acrylate, and neopentyl glycol hydroxypivalic acid. Ester di (meth) acrylate (MANDA), neopentyl glycol hydroxypivalate ester di (meth) acrylate (HPNDA), 1,3-butanediol di (meth) acrylate (BGDA), 1,4-butanediol di (meth) Acrylate (BUDA), 1,6-hexanediol di (meth) acrylate (HDDA), 1,9-nonanediol di (meth) acrylate, diethylene glycol di (meth) acrylate DEGDA), neopentyl glycol di (meth) acrylate (NPGDA), tripropylene glycol di (meth) acrylate (TPGDA), caprolactone-modified neopentyl glycol hydroxypivalate ester di (meth) acrylate, propoxylated neopentyl glycol di (meth) A) acrylate, ethoxy-modified bisphenol A di (meth) acrylate, polyethylene glycol 200 di (meth) acrylate, polyethylene glycol 400 di (meth) acrylate, methylene bisacrylamide, and the like. These may be used alone or in combination of two or more.

  Examples of the trifunctional monomer include trimethylolpropane tri (meth) acrylate (TMPTA), pentaerythritol tri (meth) acrylate (PETA), triallyl isocyanate, tris (2-hydroxyethyl) isocyanurate tri (meth) acrylate And ethoxylated trimethylolpropane tri (meth) acrylate, propoxylated trimethylolpropane tri (meth) acrylate, and propoxylated glyceryl tri (meth) acrylate. These may be used alone or in combination of two or more.

  Examples of the tetrafunctional or higher-functional monomer include, for example, pentaerythritol tetra (meth) acrylate, ditrimethylolpropane tetra (meth) acrylate, dipentaerythritol hydroxypenta (meth) acrylate, ethoxylated pentaerythritol tetra (meth) acrylate, penta ( (Meth) acrylate esters, dipentaerythritol hexa (meth) acrylate (DPHA) and the like. These may be used alone or in combination of two or more.

  The content of the polyfunctional monomer is preferably 0.001% by mass or more and 1% by mass or less, more preferably 0.01% by mass or more and 0.5% by mass or less based on the total amount of the bolus-forming liquid material. When the content is in the range of 0.001% by mass or more and 1% by mass or less, the elasticity and hardness of the obtained bolus can be adjusted to appropriate ranges.

-Polymerization initiator-
Examples of the polymerization initiator include a thermal polymerization initiator and a photopolymerization initiator.
The thermal polymerization initiator is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include an azo initiator, a peroxide initiator, a persulfate initiator, and a redox (oxidation-reduction) initiator. And the like.
Examples of the azo initiator include VA-044, VA-46B, V-50, VA-057, VA-061, VA-067, VA-086, 2,2′-azobis (4-methoxy-2). , 4-Dimethylvaleronitrile) (VAZO 33), 2,2′-azobis (2-amidinopropane) dihydrochloride (VAZO 50), 2,2′-azobis (2,4-dimethylvaleronitrile) (VAZO 52) ), 2,2′-azobis (isobutyronitrile) (VAZO 64), 2,2′-azobis-2-methylbutyronitrile (VAZO 67), 1,1-azobis (1-cyclohexanecarbonitrile) ( VAZO 88) (all available from DuPont Chemical), 2,2'-azobis (2-cyclopropylpropionitrile), 2,2'-azobis Methyl isobutyrate - DOO) (V-601) (manufactured by Wako Pure Chemical Industries, available from KK).

  Examples of the peroxide initiator include benzoyl peroxide, acetyl peroxide, lauroyl peroxide, decanoyl peroxide, dicetyl peroxydicarbonate, di (4-t-butylcyclohexyl) peroxydicarbonate (Perkadox 16S). ) (Available from Akzo Nobel), di (2-ethylhexyl) peroxydicarbonate, t-butylperoxypivalate (Luppersol 11) (available from Elf Atochem), t-butylperoxy-2-ethyl Hexanoate (Trigonox 21-C50) (available from Akzo Nobel), dicumyl peroxide and the like.

Examples of the persulfate initiator include potassium persulfate, sodium persulfate, ammonium persulfate, and sodium peroxodisulfate.
Examples of the redox (redox) initiator include a combination of the persulfate initiator and a reducing agent such as sodium metabisulfite and sodium bisulfite, and a system based on the organic peroxide and a tertiary amine. (Eg, a system based on benzoyl peroxide and dimethylaniline), a system based on an organic hydroperoxide and a transition metal (eg, a system based on cumene hydroperoxide and cobalt naphthate), and the like.

As the photopolymerization initiator, any substance that generates a radical by irradiation with light (particularly, ultraviolet light having a wavelength of 220 nm to 400 nm) can be used.
Examples of the photopolymerization initiator include acetophenone, 2,2-diethoxyacetophenone, p-dimethylaminoacetophenone, benzophenone, 2-chlorobenzophenone, p, p′-dichlorobenzophenone, p, p-bisdiethylaminobenzophenone, and Michler's ketone. Benzyl, benzoin, benzoin methyl ether, benzoin ethyl ether, benzoin isopropyl ether, benzoin-n-propyl ether, benzoin isobutyl ether, benzoin-n-butyl ether, benzyl methyl ketal, thioxanthone, 2-chlorothioxanthone, 2-hydroxy-2 -Methyl-1-phenyl-1-one, 1- (4-isopropylphenyl) 2-hydroxy-2-methylpropan-1-one, methylbenzoylphen Meto, 1-hydroxycyclohexyl phenyl ketone, azobisisobutyronitrile, benzoyl peroxide, and di -tert- butyl peroxide. These may be used alone or in combination of two or more.
In addition, tetramethylethylenediamine is used as an initiator of a polymerization / gelation reaction for converting acrylamide into a polyacrylamide gel.

(Bolus manufacturing method)
The bolus manufacturing method of the present invention is to manufacture a bolus using a bolus-forming liquid material containing water, minerals, and a polymerizable monomer.
The bolus-forming liquid material of the present invention is used as the bolus-forming liquid material.

  The method of manufacturing a bolus according to the present invention is roughly classified into two methods: a method using a mold and a method using a three-dimensional printer.

<Method of forming using mold>
The method of forming using the mold is a method of pouring a bolus-forming liquid material containing water, minerals, and a polymerizable monomer into a mold, and curing the bolus-forming liquid material. Based on the shape data, it is poured into a mold made by a three-dimensional printer and cured to form.

  Here, having a shape along the body surface, on the body surface to be irradiated with radiation of the individual patient, a certain shape such as a convex or concave portion for each of the concave or convex portion of the body. It means holding. This forms a bolus that fits perfectly on the patient's skin.

The three-dimensional printer is not particularly limited to a system, but is formed by injecting and curing a bolus forming liquid material, and is formed of a material or a method that does not leak the bolus forming liquid material. Preferably, an ink jet (material jet) method, an optical molding method, a laser sintering method, or the like is used effectively.
When curing using a thermal polymerization initiator, the reaction temperature is controlled according to the type of the initiator. After injecting a bolus-forming liquid material, sealing and shutting off air (oxygen), the mixture is heated to room temperature or a predetermined temperature to allow the polymerization reaction to proceed. After the polymerization is completed, the bolus is formed by removing from the mold.
In the case of curing using a photopolymerization initiator, it is necessary to irradiate the bolus-forming liquid material with energy rays such as ultraviolet rays as curing means. For this reason, the mold used is made of a material transparent to energy rays. After pouring into such a mold, sealing and shutting off air (oxygen), energy rays are irradiated from the outside of the mold. After the polymerization is completed in this way, a bolus is formed by removing the mold from the mold.

  For example, when producing a mold conforming to the breast shape, CT data of the breast of the subject (patient) is acquired and converted into three-dimensional (3D) data based on the acquired CT data. On the basis of this data, a male type 121 for forming a three-dimensional bolus for a patient's breast shown in FIG. 7 is produced by a three-dimensional printer. A female mold 122 for forming a three-dimensional breast bolus shown in FIG. 8 is produced by a three-dimensional printer using the patient's personal data. As shown in FIG. 9, a gap 123 is formed between the produced male type 121 and female type 122 by combining them. When the liquid material for forming a bolus of the present invention is injected into the gap 123 and cured, a three-dimensional bolus for breast 124 shown in FIG. 10 can be formed.

<Method of forming directly using a three-dimensional printer>
The modeling using the three-dimensional printer involves directly modeling the three-dimensional printer using the liquid material for forming a bolus.
It is preferable that the three-dimensional printer is an ink-jet type three-dimensional printer or a stereolithography type three-dimensional printer. By using these methods, composition distribution and shape control can be performed according to the condition of the treatment site of the patient, and a bolus having a distribution of radiation transmittance can be formed.

For example, using the personal data of the subject (patient), it is possible not only to have a shape along the body surface to be irradiated, but also to provide a radiation transmittance distribution as needed.
In this case as well, it is created based on the data of the individual patient.
For example, when producing a mold conforming to the breast shape, CT data of the breast is acquired and converted into three-dimensional (3D) data based on the CT data so that a male and female mold can be produced. Based on the 3D data, a bolus is directly produced by a three-dimensional printer.
The three-dimensional printer is preferably a system capable of printing a bolus material, and a system in which ink is ejected by an ink jet (material jet) system or a dispenser system and cured by UV light is effectively used. In the case of this method, since a plurality of materials for forming the bolus can be used, the composition of the entire bolus is not the same but a distribution of the composition can be provided. In particular, a composition distribution can be provided so that the transmittance of X-rays can be controlled according to the affected part of the patient to be treated. This is an effective method such as not damaging normal cells other than cancer cells as much as possible.

Here, the inkjet (IJ) type three-dimensional printer 10 as shown in FIG. 11 uses a head unit in which inkjet heads are arranged to support the liquid material for bolus formation from the liquid material ejecting head unit 11 for the molded object. The support-forming liquid material is ejected from the body-use liquid material ejecting head units 12, 12, and the bolus-forming liquid material and the support-forming liquid material are laminated while being cured by the adjacent ultraviolet irradiators 13, 13.
In order to keep the gaps between the liquid material jet head units 11 and 12 and the ultraviolet irradiation device 13 and the molded body (bolus) 17 and the support 18 constant, the layers are stacked while the stage 15 is lowered according to the number of times of stacking.
In the three-dimensional printer 10, the ultraviolet irradiators 13 and 13 are used when moving in either direction of the arrows A and B, and the surface of the laminated support-forming liquid material is heated by the heat generated by the ultraviolet irradiation. Is smoothed, and as a result, the dimensional stability of the bolus can be improved.
After the shaping, the bolus 17 and the support 18 are pulled apart in a horizontal direction as shown in FIG. 12, and the support 18 is peeled off as a single piece, so that the bolus 17 can be easily taken out.

  As shown in FIG. 13, in the stereolithography three-dimensional printer, a bolus forming liquid material is stored in a liquid tank 24, and an ultraviolet laser beam 23 emitted from a laser light source 21 is applied to a surface 27 of the liquid tank by a laser scanner 22. To form a cured product on the modeling stage 26. The molding stage 26 is lowered by the operation of the piston 25, and this is sequentially repeated to obtain a bolus.

  Hereinafter, examples of the present invention will be described, but the present invention is not limited to these examples.

(Example 1)
-Preparation of mold-
CT data of the breast surface of the patient (the subject) was used and converted into data for three-dimensional (3D) printing based on the CT data. Based on this data, a male type 121 and a female type 122 for a three-dimensional bolus for a breast as shown in FIGS. 7 and 8 were produced using an aziristor manufactured by KEYENCE CORPORATION as an inkjet stereolithography apparatus.

-Preparation of liquid material for bolus formation-
First, a synthetic hectorite having a composition of [Mg _5.34 Li _0.66 Si ₈ O ₂₀ (OH) ₄ ] Na ⁻ _0.66 as a water-swellable layered clay mineral while stirring 200 parts by mass of pure water. 15 parts by mass of Laponite XLG (manufactured by RockWood) were added little by little, and further 0.8 parts by mass of 1-hydroxyethane-1,1-diphosphonic acid was added, followed by stirring to prepare a dispersion.
Next, as a polymerizable monomer, 20 parts by mass of acryloylmorpholine (manufactured by KJ Chemicals Co., Ltd.) obtained by passing through a column of activated alumina and removing a polymerization inhibitor from the obtained dispersion, and light acrylate 9EG-A (Kyoeisha Chemical Co., Ltd.) 1 part by mass (manufactured by Co., Ltd.).
Next, while cooling in an ice bath, 15 parts by mass of a 2% by weight aqueous solution of sodium peroxodisulfate (manufactured by Wako Pure Chemical Industries, Ltd.) was added, and tetramethylethylenediamine (manufactured by Wako Pure Chemical Industries, Ltd.) was further added. Was added, and after stirring and mixing, deaeration under reduced pressure was carried out for 10 minutes. Subsequently, filtration was performed to remove impurities and the like, and a homogeneous bolus-forming liquid material was obtained.

-Production of three-dimensional bolus for breast-
The male mold 121 and the female mold 122 prepared above were combined as shown in FIG. 9, and the bolus-forming liquid material was poured into the mold, closed with a lid, and cured at room temperature for 6 hours. After curing, it was removed from the mold and washed with water to obtain a three-dimensional bolus for breast.

(Example 2)
A three-dimensional bolus for breast was prepared in the same manner as in Example 1 except that glycerin was used to replace 50 parts by mass of 200 parts by mass of pure water.

(Example 3)
In Example 2, except that 20 parts by mass of acryloylmorpholine was replaced with 10 parts by mass of N-dimethylacrylamide (manufactured by Wako Pure Chemical Industries, Ltd.) as a polymerizable monomer in the same manner as in Example 2, A three-dimensional bolus for the breast was made.

(Example 4)
A plastic coat # 100 (manufactured by Daikyo Chemical Co., Ltd.) was applied to the bolus surface prepared in Example 1 by a dip coating method to form a film having a thickness of 30 μm.

(Comparative Example 1)
A bolus-forming liquid material was prepared according to the example of JP-A-11-222293. That is, 398.4 parts by mass of a polysiloxane (viscosity at 25 ° C: 1200 cp) which is a main agent having a reactive vinyl group, and methylhydrogenpolysiloxane (viscosity: 20 cp at 25 ° C) which is a crosslinking agent having a hydrogen-silicon bond. 6 parts by mass and 0.06 parts by mass of a 1% by mass chloroplatinic acid alcohol solution as a curing catalyst were mixed, stirred, and then completely defoamed at room temperature to prepare an addition reaction type silicone gel material.
An attempt was made to form a bolus using this liquid material in the same manner as in Example 1. However, this liquid material had a very high viscosity, could not be poured into a mold, and could not form a bolus. .

(Comparative Example 2)
A bolus forming liquid material was prepared according to Example 1 of JP-A-6-47030. That is, polyvinyl alcohol having an average degree of polymerization of about 2,000 and a degree of saponification of 89 mol% was dissolved in water containing 0.9% by mass of NaCl. At this time, in order to dissolve the polyvinyl alcohol, it was heated to 60 ° C. and dissolved. Using this liquid material, it was poured into a mold in the same manner as in Example 1, molded, and subjected to nine times of freezing and thawing to form a bolus.

(Comparative Example 3)
A bolus forming liquid material was prepared according to the example of Japanese Patent No. 2999184. That is, 4.0 g of carrageenan, 3.0 g of locust bean gum, and 3.0 g of xanthan gum were added and dissolved by heating at 80 ° C. for 10 minutes with stirring. Using this liquid material, it was poured into a mold in the same manner as in Example 1, molded, and cooled to form a bolus.

<Evaluation>
The following test items were evaluated for the three-dimensional bolus for breast prepared in Examples 1 to 4 and Comparative Examples 2 to 3. The results are shown in Table 1.

(1) Appearance [Evaluation criteria]
：: high transparency, no air bubbles mixed △: slightly low transparency ×: low transparency

(2) Dimensionality [Evaluation criteria]
：: Thickness and length are uniform ×: Thickness and length are uneven

(3) Elasticity [Evaluation criteria]
◎: Moderate elasticity, no change such as tearing even when bent to 180 ° ○: Moderate elasticity ×: Low elasticity, tearing when bent to 180 °

(4) Heat resistance Each bolus was heated in hot water at 60 ° C. for 30 minutes, and then its shape and physical properties were measured and evaluated according to the following criteria.
[Evaluation criteria]
○: No change in shape and physical properties ×: Deterioration of shape and physical properties

(5) Solvent resistance After cleaning each bolus using ethanol, the shape and physical properties were measured and evaluated according to the following criteria.
[Evaluation criteria]
：: No change in shape and physical properties △: Swelled slightly ×: Deteriorated in shape and physical properties

(6) CT value The X-ray test apparatus: The CT value of each bolus was measured using Aquilion PRIME Beyond (manufactured by Toshiba Medical Co., Ltd.) and evaluated according to the following criteria.
[Evaluation criteria]
：: CT value is 0 or more and 100 or less, indicating a value close to the composition of the human body. ×: CT value is more than 100 and deviates from the composition of the human body.

(7) Preservability After storing each bolus in a sealed state (25 ° C., 50% RH) for 7 days, the shape and physical properties were measured and evaluated according to the following criteria.
[Evaluation criteria]
◎: No change in shape and physical properties ：: No change in shape, very dry (weight change rate within 3%)
×: Deterioration of shape and physical properties

(Example 5)
-Preparation of liquid material for bolus formation-
First, a synthetic hectorite having a composition of [Mg _5.34 Li _0.66 Si ₈ O ₂₀ (OH) ₄ ] Na ⁻ _0.66 as a water-swellable layered clay mineral while stirring 165 parts by mass of pure water. 16 parts by mass of Laponite XLG (manufactured by Rockwood) was added little by little, and the mixture was stirred for 3 hours to prepare a dispersion. Thereafter, 0.6 parts by mass of 1-hydroxyethane-1,1-diphosphonic acid (manufactured by Tokyo Chemical Industry Co., Ltd.) was added, and the mixture was further stirred for 1 hour. Thereafter, 30 parts by mass of glycerin (manufactured by Sakamoto Pharmaceutical Co., Ltd.) was added, and the mixture was stirred for 10 minutes.
Next, 16 parts by mass of acroylmorpholine (manufactured by KJ Chemicals Co., Ltd.), from which a polymerization inhibitor was removed by passing through a column of activated alumina, as a polymerizable monomer, was added to the obtained dispersion, and N, N-dimethylacrylamide was used. 4 parts by mass (manufactured by Wako Pure Chemical Industries, Ltd.) and 1 part by mass of light acrylate 9EG-A (manufactured by Kyoeisha Chemical Co., Ltd.) were added. Further, 1 part by mass of Emulgen SLS-106 (manufactured by Kao Corporation) as a surfactant was added and mixed.
Next, while cooling in an ice bath, 2.2 parts by mass of a 4% by mass solution of a photopolymerization initiator (Irgacure 184, manufactured by BASF) in methanol was added, and after stirring and mixing, deaeration was performed under reduced pressure for 20 minutes. . Subsequently, filtration was performed to remove impurities and the like, and a bolus-forming liquid material was obtained.

-Preparation of liquid material for forming support-
Urethane acrylate (manufactured by Mitsubishi Rayon Co., Ltd., trade name: Diabeam UK6038) 10 parts by mass, neopentyl glycol hydroxypivalate di (meth) acrylate (manufactured by Nippon Kayaku Co., Ltd., trade name: KAYARD MANDA) 90 as a polymerizable monomer 3 parts by mass of 1 part by mass of 1-hydroxycyclohexyl phenyl ketone (manufactured by BASF, trade name: Irgacure 184) as a polymerization initiator at a rotation speed of 2,000 rpm using a homogenizer (HG30, manufactured by Hitachi Koki Co., Ltd.). Dispersed until a homogeneous mixture was obtained. Subsequently, filtration was performed to remove impurities and the like, and finally vacuum deaeration was performed for 10 minutes to obtain a homogeneous liquid material for forming a support.

-3D bolus formation-
A liquid material for forming a bolus and a liquid material for forming a support are filled in an ink-jet type three-dimensional printer as shown in FIG. 11, and two ink-jet heads (GEN4, manufactured by Ricoh Industry Co., Ltd.) are charged and ejected. Then, a film was formed.
As in the case of Example 1, modeling was performed using CT data of the breast surface of the patient (the subject) and converted into data for 3D printing based on the CT data. A bolus was formed based on this data.
The bolus and the support are cured while irradiating an amount of 350 mJ / cm ^{2 with} an ultraviolet irradiation device (SPOT CURE SP5-250DB, manufactured by Ushio Inc.) to cure the bolus-forming liquid material and the support-forming liquid material. Body formation was performed.
After the shaping, the bolus 17 and the support 18 were pulled apart in the horizontal direction as shown in FIG. 12, and the support 18 was peeled off as a unit, so that the bolus 17 could be easily taken out. Thus, a three-dimensional bolus for the breast was formed.

(Example 6)
In Example 5, 0.5 part by mass of N, N-methylenebisacrylamide (manufactured by Wako Pure Chemical Industries, Ltd.) was included in 1 part by mass of light acrylate 9EG-A (manufactured by Kyoeisha Chemical Co., Ltd.) in the liquid material for forming a bolus. A three-dimensional breast bolus was produced in the same manner as in Example 5, except that the bolus was replaced with (3).

(Example 7)
Poval 205 (manufactured by Kuraray Co., Ltd.) was applied to the surface of the three-dimensional bolus for breast prepared in Example 5 by a dip coating method to form a film having a thickness of 30 μm.

(Example 8)
Using the bolus-forming liquid material used in Example 5, a laser (COHERENT, wavelength 375 nm) was used to irradiate 350 mJ / cm ² of light with a stereolithography three-dimensional printer shown in FIG. By curing the bolus forming liquid material, a three-dimensional bolus for breast was formed.

<Evaluation>
Various characteristics were evaluated for each bolus produced in Examples 5 to 8 in the same manner as in Example 1. The results are shown in Table 2.

(Example 9)
-Preparation of liquid material A for bolus formation-
A bolus-forming liquid material was prepared in the same manner as in Example 5, and was used as a bolus-forming liquid material A.

-Preparation of bolus forming liquid material B-
First, 30 parts by mass of glycerin (manufactured by Sakamoto Pharmaceutical Co., Ltd.) was added to 165 parts by mass of pure water, and the mixture was stirred for 10 minutes.
Next, 1 part by mass of Emulgen SLS-106 (manufactured by Kao Corporation) was added and mixed as a surfactant.
Further, 2.2 parts by mass of a 4% by mass solution of a photopolymerization initiator (Irgacure 184, manufactured by BASF) in methanol was added, and after stirring and mixing, deaeration was performed under reduced pressure for 20 minutes. Subsequently, filtration was performed to remove impurities and the like, and a bolus-forming liquid material B was obtained.

-Preparation of liquid material for forming support-
In the same manner as in Example 5, a liquid material for forming a support was prepared.

-3D bolus formation-
The bolus-forming liquid material A, the bolus-forming liquid material B, and the bolus-forming liquid material B are provided in an ink-jet type three-dimensional printer (in this case, a plurality of heads for discharging the bolus-forming liquid material) as shown in FIG. A liquid material for forming a support was filled, and charged into three inkjet heads (GEN4, manufactured by Ricoh Industry Co., Ltd.), and sprayed to form a film.
The modeling assumed a diseased part (cancer cell) as shown in FIG. 1 and prepared flat 3D print data. At this time, as shown in FIG. 4, the mixing mass ratio of the bolus-forming liquid material A and the bolus-forming liquid material B was changed so that the absorptivity of X-rays changed near the center of the bolus.
Specifically, the white area at the center of the bolus is 100% bolus-forming liquid material A, and the black area outside the bolus is 1: 1 (mass ratio) bolus-forming liquid material A: bolus-forming liquid material B. , And a gradation was provided during that time.
In the same manner as in Example 5, the liquid material for forming a bolus and the liquid material for forming a support are cured by irradiating a light amount of 350 mJ / cm ² with an ultraviolet irradiation machine (SPOT CURE SP5-250DB, manufactured by Ushio Inc.). While forming, a formed body (bolus) and a support were formed. Thus, a 3D bolus having a composition distribution was formed.
When the bolus produced in Example 9 was irradiated with X-rays, an X-ray transmittance distribution as shown in FIG. 4 was obtained, and the irradiation dose of X-rays was high at the center of the cancer cell and low at the periphery. Was.

(Example 10)
A 3D bolus was produced in the same manner as in Example 9, except that the thickness of the bolus at the portion corresponding to the outer region of the cancer cells was changed as shown in FIG.
The 3D bolus of Example 10 was able to further reduce the amount of X-ray irradiation around the cancer cells, as compared with the 3D bolus prepared in Example 9.

Aspects of the present invention are, for example, as follows.
<1> a bolus to be applied to patients undergoing radiation therapy,
A bolus having a shape along a body surface to be irradiated with radiation of the patient and a radiation transmittance distribution corresponding to an affected part of the patient.
<2> The bolus according to <1>, comprising a hydrogel.
<3> The bolus according to <2>, wherein the hydrogel is a hydrogel containing water, a polymer, and a mineral.
<4> The bolus according to <3>, wherein the bolus includes a hydrogel in which the water is contained in a three-dimensional network structure formed by complexing the polymer and the mineral.
<5> The bolus according to any one of <3> to <4>, further containing a water-soluble organic solvent.
<6> The bolus according to <5>, wherein the water-soluble organic solvent is a polyhydric alcohol.
<7> The bolus according to <6>, wherein the polyhydric alcohol is at least one of glycerin and propylene glycol.
<8> The bolus according to any one of <6> to <7>, wherein the content of the organic solvent is 10% by mass or more and 50% by mass or less based on the total amount of the bolus.
<9> The bolus according to any one of <1> to <8>, wherein the mineral is a water-swellable layered clay mineral.
<10> The bolus according to <9>, wherein the water-swellable layered clay mineral is a water-swellable hectorite.
<11> The bolus according to any one of <1> to <10>, having a film on the surface.
<12> A bolus-forming liquid material containing water, a mineral, and a polymerizable monomer.
<13> The bolus-forming liquid material according to <12>, further including a polymerization initiator.
<14> The bolus-forming liquid material according to <13>, wherein the polymerization initiator is one of a thermal polymerization initiator and a photopolymerization initiator.
<15> A bolus-forming liquid material containing water, minerals, and a polymerizable monomer is poured into a mold made by a three-dimensional printer based on shape data of a patient's skin surface, and cured to form. Bolus manufacturing method.
<16> A bolus-forming liquid material containing water, minerals, and a polymerizable monomer is ejected by an inkjet head based on shape data of a patient's skin surface and shape data of an affected part of a patient, and is cured by ultraviolet light. A bolus manufacturing method characterized in that the bolus is formed by an ink-jet type three-dimensional printer.
<17> Using a liquid material for bolus formation containing water, minerals, and polymerizable monomers, formed with a stereolithography three-dimensional printer based on the shape data of the patient's skin surface and the shape data of the affected part of the patient. A bolus manufacturing method.
<18> The method for producing a bolus according to any one of <15> to <17>, wherein the bolus-forming liquid material contains a polymerization initiator.
<19> The method for producing a bolus according to <18>, wherein the polymerization initiator is one of a thermal polymerization initiator and a photopolymerization initiator.

  The bolus according to any one of <1> to <11>, the liquid material for forming a bolus according to any one of <12> to <14>, and any one of <15> to <19>. According to the method for manufacturing a bolus, the above problems in the related art can be solved and the object of the present invention can be achieved.

REFERENCE SIGNS LIST 30 modeling device 31 ink ejecting head unit for modeling object 32 ink ejecting head unit for support 33 UV irradiator 34 modeling substrate support substrate 35 stage 36 smoothing member 37 modeling object (bolus)
38 Support (support material)
41 Laser Light Source 42 Laser Scanner 43 Laser Beam 44 Bathtub 45 Piston 46 Modeling Stage 47 Ink Liquid Level 48 Modeled Product (Bolus: Laser-cured Part)
110 A mold for forming a bolus 111 A bolus 112 A mold for forming a bolus 113 Chest (breast)
114 Type adapted to chest surface 121 Male type for forming 3D bolus for breast 122 Female type for forming 3D bolus for breast 123 Gap when male and female types are combined 124 3D bolus for breast

Japanese Patent Publication No. 3-26994 Japanese Patent Publication No. 6-47030 Japanese Patent No. 2999184 JP-A-11-222293 JP-A-3-115897

Claims (4)

A bolus for application to a patient undergoing radiation therapy,
Shape along the body surface to be irradiated target of the patient, and the transmittance distribution of the radiation corresponding to the affected part of the patient possess,
The bolus is made of a hydrogel,
The hydrogel is a hydrogel containing water, a polymer, and a mineral,
The bolus includes a hydrogel in which the water is contained in a three-dimensional network formed by complexing the polymer and the mineral . The bolus according to claim 1, further comprising a water-soluble organic solvent. The bolus according to claim 2, wherein the water-soluble organic solvent is a polyhydric alcohol. The bolus according to any one of claims 1 to 3, having a coating on the surface.