JP6915708B2 - Bolus manufacturing method and liquid material for bolus formation - Google Patents

Description

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

It is widely practiced to irradiate the human body with radiation such as X-rays, γ-rays, electron beams, neutron rays, and α-rays, or laser beams, and use them for the treatment of diseases such as cancer. In general, when a substance is irradiated with radiation, the original amount of radiation decreases exponentially as it goes deeper, but the scattered radiation increases relatively as it goes deeper, and its direction varies.

Especially in high-energy radiation, since the direction of the rebounding electrons (scattered rays) is mainly in the front, the scattering to the side is reduced, and the dose at a depth higher than the surface dose is maximized. If treatment is performed without considering the nature of such radiation in the skin, it may have a harmful effect on normal tissues other than the target (affected area) due to unnecessary radiation irradiation.
In order to prevent this, bolus, which is used to flatten the irregular surface of the human body or fill the defective part, irradiates only the target with a substance equivalent to human tissue. The method of doing is done.
Here, the substance equivalent to the human tissue means a substance that exhibits substantially the same properties as the human tissue in terms of absorption or scattering of radiation.

In general, a bolus worthy of practical use is (1) a substance equivalent to human tissue, (2) homogeneous, (3) excellent in plasticity, appropriately elastic, and to a living body. Shape compatibility, good adhesion, (4) no toxicity, (5) no energy change, (6) uniform thickness, (7) no air contamination, ( It is necessary to satisfy the characteristics and functions such as 8) high transparency and (9) ease of disinfection.

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

An object of the present invention is to provide a bolus that can adhere to the skin surface of a patient without gaps and has an appropriate radiation transmittance distribution corresponding to the affected part of the patient.

The bolus of the present invention as a means for solving the above-mentioned problems is a bolus for being applied to a patient undergoing radiotherapy.
It has a shape along the surface of the body to be irradiated by 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 gaps 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 area of a patient with X-rays using a bolus. FIG. 2 is a diagram when X-rays are irradiated using a homogeneous bolus. FIG. 3 is a diagram when X-rays are irradiated using a bolus having a composition distribution. FIG. 4 is a top view of a bolus having a composition distribution and a conceptual diagram showing the amount of transmitted light of X-rays. FIG. 5 is a conceptual diagram in which the shape of the bolus is changed. FIG. 6 is a schematic view showing an example of a state in which a water-swellable layered clay mineral as a mineral and the water-swellable layered clay mineral are dispersed in water. FIG. 7 is a schematic view of a male breast bolus produced by a three-dimensional printer. FIG. 8 is a schematic view of a female breast bolus manufactured by a three-dimensional printer. FIG. 9 is a schematic view combining a breast bolus produced by a three-dimensional printer. FIG. 10 is a schematic view of the bolus taken out from the mold. FIG. 11 is a schematic view of a three-dimensional printer for producing a bolus. FIG. 12 is a schematic view of a bolus produced by a three-dimensional printer peeled off from a support material. FIG. 13 is a schematic view of a three-dimensional printer having another configuration for producing a bolus.

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

Since the bolus of the present invention has a flat plate-like shape produced by using a mold in the conventional bolus, it is difficult to completely adhere to the skin surface of the patient without any gaps, and by such a method. Since the produced bolus itself does not change the composition of the entire bulk and has one characteristic, the radiation transmittance is controlled only by the thickness of the bolus, so the shape is restricted and it is not easy to use. It is based on.
Further, in the technique described in Patent Document 5, two boluses are used in combination, the composition of these boluses is uniform, and the radiation transmittance is not controlled. It only filters non-transparent. On the other hand, in the present invention, one bolus is used, a radiation transmittance distribution is provided by controlling the composition and shape, and the irradiation amount distribution of the radiation passing through the distribution is controlled. For this reason, the two are essentially different.

<Shape along the body surface to be irradiated by the patient>
The bolus produced by the present invention uses the patient's personal data and has a shape along the body surface to be irradiated by the patient. As a result, a bolus that fits the patient's skin perfectly can be formed.
Here, having a shape along the body surface means a certain shape that is a convex portion or a concave portion with respect to each of the concave portion or the convex portion of the body on the body surface to be irradiated by the individual patient. Means holding.

<Radiation transmittance distribution corresponding to the affected area of the patient>
The bolus produced by 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 non-cancer cells.
Here, the advantages of having a radiation transmittance distribution will be described. For example, treatment by X-ray irradiation has the following drawbacks.
-Body surfaces other than cancer cells are affected by more radiation than cancer cells, and cells behind cancer cells are also affected.
・ The shape cannot be processed.
・ When a heart or lung disorder occurs, it is necessary to avoid deadly organs and irradiate.

Here, FIG. 1 shows how the affected portion 32 of the patient is irradiated with X-rays. A bolus 30 is placed on the skin surface 31 of the affected area 32, and X-rays are irradiated from the surface.
As shown in FIG. 2, when the conventional bolus 33 is used, the composition of the bolus 33 is homogeneous, so that the X-ray irradiation depth can be controlled, but it is uniformly controlled. Therefore, it works only to uniformly control the peak of the incident X-ray even in the depth direction and the surrounding area. This is the point that the above-mentioned shape cannot be processed. Therefore, cells other than cancer cells and the body surface are strongly affected by radiation (X-rays). 34 in FIG. 2 shows X-rays (homogeneous) transmitted through the bolus.
On the other hand, the case where the X-ray transmittance distribution is given is shown in FIG. 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. Although the thickness is constant and only the composition is changed in FIG. 3, the film thickness can be changed at the same time, and by combining the two, it becomes possible to irradiate the cancer cells with focused X-rays. .. This makes it possible to reduce adverse effects on non-cancer cells. 36 in FIG. 3 shows X-rays (having a distribution) that have passed through the bolus.
In order to form the X-ray transmittance distribution, as shown below, there are two methods, one is to provide a bolus composition distribution, the other is to control by shape, or a combination of both.

-Composition distribution-
In order to form the X-ray transmittance distribution in the bolus as described above, there is a method of imparting a composition distribution constituting the bolus.
FIG. 4 is a diagram showing a state in which the bolus 35 with the composition distribution is viewed from above and the X-ray transmission amount distribution. The black part of the bolus has a composition that attenuates X-rays in a large proportion, and the white portion has a large proportion of transmission. The X-rays that have passed through such a bolus have high intensity in the central portion and can be focused on and irradiated to cancer cells and the like.
This can be achieved by using, for example, an inkjet three-dimensional printer as a method for forming the composition distribution, and using a plurality of liquid materials for forming bolus. In particular, in the hydrogel used in the present invention, the relationship between the composition (water content) and the X-ray transmittance is uniquely determined, and the transmittance can be easily controlled.

-Shape control-
There is also a shape control method for imparting an X-ray transmittance distribution.
For example, by forming the shape as shown in FIG. 5, it is possible to reduce the amount of irradiation to the peripheral portion of the cancer cell.
As described above, 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 modeling method using a three-dimensional printer that can produce such an epoch-making means, which is an important point of the present invention.

The bolus of the present invention comprises a hydrogel, which comprises water, a polymer and a mineral, preferably containing an organic solvent, and more preferably containing other components as needed.
In the bolus, the solvent is contained in a three-dimensional network structure formed by cross-linking the mineral dispersed in an organic solvent and the polymer polymerized with a polymerizable monomer to form a composite. It preferably consists of a gel.
The bolus is produced using a bolus-forming liquid material containing water, minerals, and a polymerizable monomer, which will be described later.

-Polymer-
Examples of the polymer include polymers 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), a heteropolymer (copolymer), may be modified, or a known functional group may be introduced. It may be in the form of a salt, but a homopolymer is preferable.
In the present invention, the water solubility of the polymer means, for example, that when 1 g of the polymer is mixed with 100 g of water at 30 ° C. and stirred, 90% by mass or more of the polymer dissolves.

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

-Water-
As the water, for example, pure water such as ion-exchanged water, ultra-filtered water, reverse osmosis water, distilled water, or ultrapure water can be used.
Other components such as an organic solvent may be dissolved or dispersed in the water depending on the purpose of imparting moisturizing property, antibacterial property, conductivity, hardness adjustment and the like.

-Minerals-
The mineral is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include water-swellable layered clay minerals.
As shown in the upper figure of FIG. 6, the water-swellable layered clay mineral is dispersed in water in a single layer state, and exhibits a state in which two-dimensional disk-shaped crystals having a unit cell in the crystal are stacked. When the water-swellable layered clay mineral is dispersed in water, as shown in the lower figure of FIG. 6, each single layer state is separated into disk-shaped crystals.

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 from the viewpoint of obtaining a highly elastic bolus.
The water-swellable hectorite may be appropriately synthesized or may be a commercially available product. Examples of the commercially available product include synthetic hectorite (Raponite XLG, manufactured by RockWood), SWN (manufactured by Coop Chemical Ltd.), and fluorinated hectorite SWF (manufactured by Coop Chemical Ltd.). Among these, synthetic hectorite is preferable from the viewpoint of elastic modulus of bolus.
The water swelling property means that water molecules are inserted between layers of layered clay minerals 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, and more preferably 1% by mass or more and 25% by mass or less, based on the total amount of the bolus, from the viewpoint of elastic modulus and hardness of the bolus.

-Organic solvent-
The organic solvent is contained to enhance the moisturizing property of the bolus.
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. , Amids such as dimethylacetamide; ketones or ketone alcohols such as acetone, methylethylketone, diacetone alcohols; ethers such as tetrahydrofuran and dioxane; ethylene glycol, propylene glycol, 1,2-propanediol, 1,2-butanediol , 1,3-butanediol, 1,4-butanediol, diethylene glycol, triethylene glycol, 1,2,6-hexanetriol, thioglycol, hexylene glycol, polyhydric alcohols such as glycerin; polyethylene glycol, polypropylene glycol Polyalkylene glycols such as; lower alcohol ethers of polyhydric alcohols such as ethylene glycol monomethyl (or ethyl) ether, diethylene glycol methyl (or ethyl) ether, triethylene glycol monomethyl (or ethyl) ether; monoethanolamine, diethanolamine, etc. Alkanolamines such as triethanolamine; N-methyl-2-pyrrolidone, 2-pyrrolidone, 1,3-dimethyl-2-imidazolidinone and the like can be mentioned. These may be used alone or in combination of two or more. Among these, polyhydric alcohol is preferable, and glycerin and propylene glucol are more preferable from the viewpoint of moisturizing property.
The content of the organic solvent is preferably 10% by mass or more and 50% by mass or less with respect to the total amount of the bolus. When the content is 10% by mass or more, the effect of preventing drying can be sufficiently obtained. Further, when it 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, the deviation from the composition of the human body is small, and a good function as a bolus can be obtained.

-Other ingredients-
The other components are not particularly limited and may be appropriately selected depending on the intended purpose. For example, a phosphonic acid compound such as 1-hydroxyethane-1,1-diphosphonic acid, a stabilizer, a surface treatment agent, etc. Examples thereof include polymerization initiators, colorants, viscosity regulators, adhesive imparting agents, antioxidants, antiaging agents, cross-linking accelerators, ultraviolet absorbers, plasticizers, preservatives, and dispersants.

-Film-
It is effective to provide a film on the surface of the bolus for the following three purposes.
(1) Maintain the shape of the bolus.
(2) Improve the storage stability (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 to give the film an elastic force in order to prevent the bolus from collapsing due to its own weight. The difference in Young's modulus of the bolus with and without the film is preferably 0.01 MPa or more.
The material for forming the film is not particularly limited and may be appropriately selected depending on the intended purpose. For example, polyester, polyolefin, polyethylene terephthalate, PPS, polypropylene, polyvinyl alcohol (PVA), polyethylene, polyvinyl chloride, cellophane , Acetate, polystyrene, polycarbonate, nylon, polyimide, fluororesin, paraffin wax and the like. These may be used alone or in combination of two or more. Further, as the film forming material, a commercially available product can be used, and examples of the commercially available product include Plasticoat # 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 intended purpose, but is preferably 100 μm or less, and 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 there are scratches or surface roughness on the surface of the bolus, the appearance can be supplemented by a film. In addition, the surface film serves as a sacrificial layer, so that the internal bolus can be protected.
In addition, since the surface of the bolus cannot be marked, etc., by forming a film on the surface of the bolus, it is possible to write the procedure at the time of radiotherapy, the patient name, etc., and thus function as a bolus. Gender can be imparted.

The method for forming the film is not particularly limited and may be appropriately selected depending on the intended 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 the bolus. Examples of the coating method include brushing, spraying, and dipping coating.
Further, a method of using a heat-shrinkable film as the film-forming material and laminating on the surface of the hydrogel structure can be mentioned.
Further, the film-forming material may be dissolved in a solvent to form a film at the same time when the bolus is formed by the three-dimensional printer using the bolus-forming liquid material.
In either case, adhesion to the skin is important, so it is possible to form a film that does not impair the shape of the bolus surface created based on the three-dimensional data of the body surface to be irradiated by the individual subject. It is essential.

In order to improve the storage stability of the bolus, it is necessary to improve the drying resistance and antiseptic property.
In order to improve the drying resistance, it is effective to reduce the water vapor transmission rate and the oxygen permeability of the film. Specifically, the water vapor transmission rate (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, it is preferable that the film contains an antiseptic. The preservative is not particularly limited and may be appropriately selected depending on the intended purpose. For example, dehydroacetate, sorbate, benzoate, sodium pentachlorophenol, 2-pyridinethiol-1-oxide can be selected. Examples thereof include 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 intended purpose.
The bolus has a flat plate shape, and when it is brought into close contact with the surface of the human body, it is used by pressing it against the skin, or it is cut into an appropriate size and joined together.

In the bolus of the present invention, the CT value (HU) measured by the computed tomography method is in the range of -100 or more and 100 or less, preferably 0 or more and 100 or less, and more preferably 0 or more and 70 or less. ..
The CT value is a value calibrated with 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 it is desirable that the bolus has a body composition close to that of the bolus.
Even if it says body composition, the CT value differs depending on the part. It is known that the muscles are about 35 to 50, the internal organs are also different depending on the site, the liver is about 45 to 75, and the pancreas is about 25 to 55.
Further, fat has a value of about -50 to -100, and blood has a value of about 10 to 30.
Therefore, although it depends on the irradiation site, when the CT value is -100 or more and 100 or less, a bolus exhibiting substantially the same properties as human tissue in terms of radiation absorption or scattering can be obtained. More preferably, it is 0 or more and 100 or less, and further 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 composed mainly 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, the composition ratio of the materials constituting the hydrogel (the abundance ratio of polymers and minerals to water, the mixing ratio of water and an organic solvent) can be arbitrarily changed 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 radiotherapy.
As described above, the bolus composed of hydrogel has the physical properties and properties necessary for the bolus, and hydrogel is listed as one of the most excellent materials as a material constituting the bolus.

(Liquid material for bolus formation)
The liquid material for bolus formation of the present invention contains water, minerals, and a polymerizable monomer, preferably 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 liquid material for forming the bolus, the same ones as the bolus can be used.

-Polymerizable monomer-
The polymerizable monomer is a compound having one or more unsaturated carbon-carbon bonds, and examples thereof include a monofunctional monomer and a polyfunctional monomer. Further, examples of the polyfunctional monomer include a bifunctional monomer, a trifunctional monomer, a tetrafunctional or higher functional monomer, and the like.

The monofunctional monomer is a compound having one unsaturated carbon-carbon bond, for example, acrylamide, N-substituted acrylamide derivative, N, N-di-substituted acrylamide derivative, N-substituted methacrylamide derivative, N, N-. Examples thereof include di-substituted 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-di-substituted acrylamide derivative, N-substituted methacrylamide derivative, or N, N-di-substituted methacrylamide derivative include N, N-dimethylacrylamide (DMAA) and N-. Examples include isopropylacrylamide.

Examples of the other monofunctional monomer include 2-ethylhexyl (meth) acrylate (EHA), 2-hydroxyethyl (meth) acrylate (HEA), 2-hydroxypropyl (meth) acrylate (HPA), and acryloylmorpholine (ACMO). ), Caprolactone-modified tetrahydrofurfuryl (meth) acrylate, isobonyl (meth) acrylate, 3-methoxybutyl (meth) acrylate, tetrahydrofurfuryl (meth) acrylate, lauryl (meth) acrylate, 2-phenoxyethyl (meth) acrylate, Examples thereof include isodecyl (meth) acrylate, isooctyl (meth) acrylate, tridecyl (meth) acrylate, caprolactone (meth) acrylate, ethoxylated nonylphenol (meth) acrylate, and 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 and the like is an advantageous constituent component for maintaining the strength of the bolus.

The content of the monofunctional monomer is not particularly limited and may be appropriately selected depending on the intended purpose, but is preferably 1% by mass or more and 10% by mass or less with respect to the total amount of the liquid material for forming a bolus. % Or more and 5% by mass or less are more preferable. 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 forming the bolus is maintained and the stretchability of the bolus is improved. The stretchability refers to a property that stretches when the bolus is pulled and does not break.

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. Esterdi (meth) acrylate (MANDA), neopentyl glycol hydroxypivalate 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 hydroxypivalate neopentyl glycol ester di (meth) acrylate, propoxylated neopentyl glycol di (meth) acrylate, ethoxy-modified bisphenol A di (meth) Examples thereof include acrylate, polyethylene glycol 200 di (meth) acrylate, polyethylene glycol 400 di (meth) acrylate, and methylenebisacrylamide. 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, and tris (2-hydroxyethyl) isocyanurate tri (meth) acrylate. , Eethoxylated trimethylolpropane tri (meth) acrylate, propoxylated trimethylolpropane tri (meth) acrylate, propoxylated glyceryl tri (meth) acrylate and the like. These may be used alone or in combination of two or more.

Examples of the tetrafunctional or higher functional monomer include pentaerythritol tetra (meth) acrylate, ditrimethylolpropane tetra (meth) acrylate, dipentaerythritol hydroxypenta (meth) acrylate, ethoxylated pentaerythritol tetra (meth) acrylate, and penta (pentaerythritol tetra (meth) acrylate). Examples thereof include meta) acrylate ester and dipentaerythritol hexa (meth) acrylate (DPHA). 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, and more preferably 0.01% by mass or more and 0.5% by mass or less, based on the total amount of the liquid material for forming a bolus. When the content is in the range of 0.001% by mass or more and 1% by mass or less, the elastic modulus and hardness of the obtained bolus can be adjusted in an appropriate range.

-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. For example, an azo-based initiator, a peroxide initiator, a persulfate initiator, and a redox (oxidation-reduction) initiator. And so on.
Examples of the azo-based 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 (methylisobutyrate) (V-601) (Wako Pure Chemicals) (Available from Kogyo Co., Ltd.).

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

Examples of the persulfate initiator include potassium persulfate, sodium persulfate, ammonium persulfate, sodium peroxodisulfate and the like.
Examples of the redox (oxidation-reduction) initiator include a combination of the persulfate initiator and a reducing agent such as sodium metahydrosulfate and sodium hydrogen sulfite, and a system based on the organic peroxide and a tertiary amine. Examples include benzoyl peroxide and dimethylaniline-based systems, organic hydroperoxide and transition metal-based systems (eg, cumene hydroperoxide and cobalt naphthate-based systems), and the like.

As the photopolymerization initiator, any substance that generates radicals by irradiation with light (particularly ultraviolet rays 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 ketone. , Phenyl, benzoin, benzoin methyl ether, benzoin ethyl ether, benzoin isopropyl ether, benzoin-n-propyl ether, benzoin isobutyl ether, benzoin-n-butyl ether, benzylmethyl ketal, thioxanthone, 2-chlorothioxanthone, 2-hydroxy-2 -Methyl-1-phenyl-1-one, 1- (4-isopropylphenyl) 2-hydroxy-2-methylpropan-1-one, methylbenzoylformate, 1-hydroxycyclohexylphenylketone, azobisisobutyronitrile , Benzoyl peroxide, di-tert-butyl peroxide and the like. These may be used alone or in combination of two or more.
Tetramethylethylenediamine is used as an initiator for a polymerization / gelation reaction using acrylamide as a polyacrylamide gel.

(Manufacturing method of bolus)
The method for producing a bolus of the present invention is to produce a bolus using a liquid material for forming a bolus containing water, minerals, and a polymerizable monomer.
As the bolus-forming liquid material, the bolus-forming liquid material of the present invention is used.

The method for producing a bolus of the present invention is roughly divided into two methods, a method of forming using a mold and a method of directly forming using a three-dimensional printer.

<Method of forming using a 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 on the surface of the patient's skin. Based on the shape data, it is poured into a mold produced by a three-dimensional printer and cured to form it.

Here, having a shape along the body surface means a certain shape that is a convex portion or a concave portion with respect to each of the concave portion or the convex portion of the body on the body surface to be irradiated by the individual patient. Means holding. This forms a bolus that fits snugly on the patient's skin.

The method of the three-dimensional printer is not particularly limited, but since the bolus-forming liquid material is injected and cured, the bolus-forming liquid material is formed by a material or method that does not leak. It is preferable that an inkjet (material jet) method, a stereolithography method, a laser sintering method, or the like is effectively used.
When curing with a thermal polymerization initiator, the reaction temperature is controlled according to the type of initiator. A liquid material for forming a bolus is injected, sealed to block air (oxygen), and then heated to room temperature or a predetermined temperature to allow the polymerization reaction to proceed. After the polymerization is complete, the bolus is formed by removing it from the mold.
When curing using a photopolymerization initiator, it is necessary to irradiate the bolus-forming liquid material with energy rays such as ultraviolet rays as a curing means. Therefore, the mold used is made of a material that is transparent to the energy rays. After injecting into such a mold and sealing it to block 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 it from the mold.

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

<Method of forming directly using a 3D printer>
The modeling using the three-dimensional printer is a direct modeling using the three-dimensional printer using the liquid material for forming a bolus.
It is preferable that the three-dimensional printer is an inkjet type three-dimensional printer or a stereolithography type three-dimensional printer. By using these methods, the composition distribution and the shape can be controlled according to the condition of the treatment site of the individual patient, and a bolus having a radiation transmittance distribution can be formed.

For example, using the personal data of the person to be treated (patient), it is possible to provide a radiation transmittance distribution as needed, as well as having a shape along the body surface to be irradiated.
In this case as well, it is created based on individual patient data.
For example, when producing a mold that matches the shape of the breast, CT data of the breast is acquired and converted into three-dimensional (3D) data so that a male and female mold can be produced based on the CT data. Based on this 3D data, a bolus is directly produced by a three-dimensional printer.
The three-dimensional printer preferably has a method capable of printing a bolus material, and a method of ejecting ink by an inkjet (material jet) method or a dispenser method and curing by UV light is effectively used. In the case of this method, since a plurality of materials forming the bolus can be used, it is possible to provide a distribution in the composition of the entire bolus instead of the same composition. In particular, a composition distribution capable of controlling the X-ray transmittance can be provided according to the affected area to be treated by the patient. This is an effective method that does not damage normal cells other than cancer cells as much as possible.

Here, the inkjet (IJ) type three-dimensional printer 10 as shown in FIG. 11 supports the liquid material for bolus formation from the liquid material injection head unit 11 for a model by using the head unit in which the inkjet heads are arranged. Liquid material for body injection The liquid material for forming a support is injected from the head units 12 and 12, and the liquid material for forming a bolus and the liquid material for forming a support are laminated while being cured by the adjacent ultraviolet irradiators 13 and 13.
In order to keep the gap between the liquid material injection head units 11 and 12 and the ultraviolet irradiator 13 and the modeled body (bolus) 17 and the support 18 constant, the stages 15 are laminated while being lowered according to the number of times of lamination.
In the three-dimensional printer 10, the ultraviolet irradiators 13 and 13 are used when moving in any of the directions of arrows A and B, and the surface of the laminated liquid material for forming a support is generated 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 molding is completed, when the bolus 17 and the support 18 are pulled and peeled off in the horizontal direction as shown in FIG. 12, the support 18 is peeled off as a unit, and the bolus 17 can be easily taken out.

Further, as shown in FIG. 13, in the stereolithography type three-dimensional printer, the bolus-forming liquid material is stored in the liquid tank 24, and the ultraviolet laser light 23 emitted by the laser light source 21 is emitted to the surface 27 of the liquid tank by the laser scanner 22. A cured product is produced on the modeling stage 26 by irradiating from. The modeling stage 26 is lowered by the operation of the piston 25, and this is repeated in sequence 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)
-Molding-
The CT data of the breast surface of the patient (the person to be treated) was used, and based on this, it was converted into data for three-dimensional (3D) printing. Based on this data, a male type 121 and a female type 122 for a three-dimensional breast bolus as shown in FIGS. 7 and 8 were produced using an azirister manufactured by KEYENCE CORPORATION as an inkjet stereolithography apparatus.

-Preparation of liquid material for bolus formation-
First, while stirring the pure water 200 parts by mass, as a water-swellable layered clay mineral _{[Mg 5.34 Li 0.66 Si 8 O} 20 (OH) 4] Na - 0.66 synthetic hectorite having a composition of ( Laponite XLG, manufactured by RockWood Co., Ltd.) 15 parts by mass was added little by little, 0.8 parts by mass of 1-hydroxyethane-1,1-diphosphonic acid was further added, and the mixture was stirred to prepare a dispersion.
Next, 20 parts by mass of acryloyl morpholine (manufactured by KJ Chemicals Co., Ltd.) from which the polymerization inhibitor was removed by passing through a column of activated alumina as a polymerizable monomer in the obtained dispersion was added to Light Acrylate 9EG-A (Kyoeisha Chemical Co., Ltd.). (Manufactured by Co., Ltd.) 1 part by mass was added.
Next, while cooling in an ice bath, 15 parts by mass of a 2% by mass aqueous solution of pure water of sodium peroxodisulfate (manufactured by Wako Pure Chemical Industries, Ltd.) was added, and further, tetramethylethylenediamine (manufactured by Wako Pure Chemical Industries, Ltd.) was added. Was added in an amount of 1 part by mass, and after stirring and mixing, degassing under reduced pressure was carried out for 10 minutes. Subsequently, filtration was performed to remove impurities and the like to obtain a homogeneous liquid material for bolus formation.

-Making a 3D bolus for breasts-
The male mold 121 and the female mold 122 produced above were combined as shown in FIG. 9, the liquid material for forming a bolus was poured into the mold, the lid was closed, and the curing reaction was carried out 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 the breast.

(Example 2)
In Example 1, a three-dimensional breast bolus was produced in the same manner as in Example 1 except that 50 parts by mass of 200 parts by mass of pure water was replaced with glycerin.

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

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

(Comparative Example 1)
A liquid material for forming a bolus was prepared according to an example of JP-A-11-22192. That is, 398.4 parts by mass of polysiloxane (viscosity 1200 cp at 25 ° C.), which is the main agent having a reactive vinyl group, and methylhydrodiene polysiloxane (viscosity 20 cp at 25 ° C.), which is a cross-linking agent having a hydrogen-silicon bond. 6 parts by mass and 0.06 parts by mass of a 1% by mass alcohol chloride alcohol solution as a curing catalyst were mixed, stirred, and then completely defoamed at room temperature to prepare a material for an addition reaction type silicone gel.
An attempt was made to form a bolus using this liquid material in the same manner as in Example 1, but the liquid material was so viscous that it could not be injected into the mold and the bolus could not be formed. ..

(Comparative Example 2)
A liquid material for forming a bolus 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 saponification degree 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 dissolved by heating to 60 ° C. Using this liquid material, it was injected into a mold in the same manner as in Example 1, shaped, and frozen and thawed 9 times to form a bolus.

(Comparative Example 3)
A liquid material for forming a bolus was prepared according to an 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 injected into a mold in the same manner as in Example 1, shaped, and cooled to form a bolus.

<Evaluation>
The following test items were evaluated for the three-dimensional breast bolus 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 and no air bubbles mixed in Δ: Slightly low transparency ×: Low transparency

(2) Dimensionality [evaluation criteria]
◯: Thickness and length are uniform ×: Thickness and length are non-uniform

(3) Elasticity [Evaluation criteria]
⊚: Has moderate elasticity and does not change such as tearing even when bent up to 180 degrees ○: Has moderate elasticity ×: Low elasticity and tears when bent up to 180 degrees

(4) Heat resistance After heating each bolus in hot water at 60 ° C. for 30 minutes, the 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 Each bolus was washed with ethanol, and then the shape and physical properties were measured and evaluated according to the following criteria.
[Evaluation criteria]
◯: No change in shape and physical properties △: Slightly swollen ×: Deterioration of shape and physical properties

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

(7) Preservation 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 slightly dry (weight change rate within 3%)
X: The shape and physical properties deteriorate

(Example 5)
-Preparation of liquid material for bolus formation-
First, while stirring the pure water 165 parts by mass, as a water-swellable layered clay mineral _{[Mg 5.34 Li 0.66 Si 8 O} 20 (OH) 4] Na - 0.66 synthetic hectorite having a composition of ( Laponite XLG, manufactured by RockWood Co., Ltd.) 16 parts by mass was added little by little, and the mixture was stirred for 3 hours to prepare a dispersion. After that, 0.6 parts by mass of 1-hydroxyethane-1,1-diphosphonic acid (manufactured by Tokyo Kasei Co., Ltd.) was added, and the mixture was further stirred for 1 hour. Then, 30 parts by mass of glycerin (manufactured by Sakamoto Yakuhin Kogyo Co., Ltd.) was added, and stirring was performed for 10 minutes.
Next, 16 parts by mass of acroylmorpholin (manufactured by KJ Chemicals Co., Ltd.) from which the polymerization inhibitor was removed by passing through a column of activated alumina as a polymerizable monomer was added to the obtained dispersion, N, N-dimethylacrylamide. (Manufactured by Wako Pure Chemical Industries, Ltd.) was added by 4 parts by mass, and light acrylate 9EG-A (manufactured by Kyoeisha Chemical Co., Ltd.) was added by 1 part by mass. Further, 1 part by mass of Emargen SLS-106 (manufactured by Kao Corporation) was added as a surfactant and mixed.
Next, while cooling in an ice bath, 2.2 parts by mass of a solution of 4% by mass of methanol of a photopolymerization initiator (Irgacure 184, manufactured by BASF) was added, and after stirring and mixing, degassing under reduced pressure was carried out for 20 minutes. .. Subsequently, filtration was performed to remove impurities and the like to obtain a liquid material for forming a bolus.

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

-Formation of 3D bolus-
The inkjet type three-dimensional printer as shown in FIG. 11 is filled with the liquid material for forming a bolus and the liquid material for forming a support, and two inkjet heads (manufactured by Ricoh Industry Co., Ltd., GEN4) are filled and injected. The film was formed.
As in the case of Example 1, the CT data of the breast surface of the patient (the person to be treated) was used for modeling, and the data was converted into data for 3D printing based on the CT data. Based on this data, the bolus was modeled.
The bolus and support while curing the bolus-forming liquid material and the support-forming liquid material by irradiating a light amount ^{of 350 mJ / cm 2 with} an ultraviolet irradiator (SPOT CURE SP5-250DB, manufactured by Ushio Electric Co., Ltd.). The body was formed.
After modeling, when the bolus 17 and the support 18 were pulled and peeled off in the horizontal direction as shown in FIG. 12, the support 18 was peeled off as a unit, and the bolus 17 could be easily taken out. In this way, a three-dimensional breast bolus was formed.

(Example 6)
In Example 5, 0.5 parts by mass of light acrylate 9EG-A (manufactured by Kyoeisha Chemical Co., Ltd.) in the liquid material for forming a bolus was N, N-methylenebisacrylamide (manufactured by Wako Pure Chemical Industries, Ltd.). ) Was replaced, and a three-dimensional bolus for breast was prepared in the same manner as in Example 5.

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

(Example 8)
Using the liquid material for bolus formation used in Example 5, a three-dimensional printer of the stereolithography method shown in FIG. 13 was used to irradiate a light amount of ^{350 mJ / cm 2 with a laser (manufactured by COHERENT, wavelength 375 nm).} A three-dimensional breast bolus was formed by curing the bolus-forming liquid material.

<Evaluation>
Various characteristics of each bolus prepared in Examples 5 to 8 were evaluated 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 this was designated as the bolus-forming liquid material A.

-Preparation of liquid material B for bolus formation-
First, 30 parts by mass of glycerin (manufactured by Sakamoto Yakuhin Kogyo Co., Ltd.) was added to 165 parts by mass of pure water, and stirring was performed for 10 minutes.
Next, 1 part by mass of Emargen SLS-106 (manufactured by Kao Corporation) was added as a surfactant and mixed.
Further, 2.2 parts by mass of a solution of a photopolymerization initiator (Irgacure 184, manufactured by BASF) in methanol was added in an amount of 2.2 parts by mass, and after stirring and mixing, degassing under reduced pressure was carried out for 20 minutes. Subsequently, filtration was performed to remove impurities and the like to obtain a liquid material B for forming a bolus.

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

-Formation of 3D bolus-
An inkjet type three-dimensional printer as shown in FIG. 11 (in this case, having a plurality of heads for discharging the bolus-forming liquid material), the bolus-forming liquid material A, the bolus-forming liquid material B, and the bolus-forming liquid material B. A liquid material for forming a support was filled, and three inkjet heads (GEN4 manufactured by Ricoh Industry Co., Ltd.) were filled and sprayed to form a film.
For modeling, assuming the affected area (cancer cells) as shown in FIG. 1, data for flat plate-shaped 3D printing was created. At this time, as shown in FIG. 4, the mixed mass ratio of the bolus-forming liquid material A and the bolus-forming liquid material B was changed so that the X-ray absorption rate changed from the vicinity of the center of the bolus.
Specifically, the white area in the center of the bolus is 100% of the liquid material A for bolus formation, and the black area outside the bolus is the liquid material A for bolus formation: the liquid material B for bolus formation is 1: 1 (mass ratio). It was set to be, and a gradation was provided in the meantime.
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 irradiator (SPOT CURE SP5-250DB manufactured by Ushio Electric Co., Ltd.). The modeled body (bolus) and the support were formed. In this way, a 3D bolus having a composition distribution was formed.
When the bolus prepared in Example 9 is irradiated with X-rays, the X-ray transmittance distribution as shown in FIG. 4 can be obtained, and the irradiation amount of X-rays can be obtained at a high center of the cancer cell and a low irradiation distribution at the periphery. rice field.

(Example 10)
A 3D bolus was prepared in the same manner as in Example 9 except that the thickness of the bolus in the portion corresponding to the outer region of the cancer cell 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.
It is a bolus characterized by having a shape along the body surface to be irradiated by the patient and a radiation transmittance distribution corresponding to the affected part of the patient.
<2> The bolus according to <1>, which is made of 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 contains a hydrogel in which the water is contained in a three-dimensional network structure formed by combining the polymer and the mineral.
<5> Further, the bolus according to any one of <3> to <4>, which contains 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 with respect to 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 water-swellable hectorite.
<11> The bolus according to any one of <1> to <10>, which has 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>, which further contains a polymerization initiator.
<14> The bolus-forming liquid material according to <13>, wherein the polymerization initiator is either a thermal polymerization initiator or a photopolymerization initiator.
<15> A bolus-forming liquid material containing water, minerals, and a polymerizable monomer is poured into a mold prepared by a three-dimensional printer based on the shape data of the patient's skin surface, and cured to form the liquid material. This is a method for manufacturing a bolus.
<16> A bolus-forming liquid material containing water, minerals, and a polymerizable monomer is ejected by an inkjet head based on the shape data of the patient's skin surface and the shape data of the affected part of the patient, and cured by ultraviolet light. It is a method for producing a bolus, which is characterized in that it is formed by an inkjet type three-dimensional printer.
<17> Using a liquid material for bolus formation containing water, minerals, and polymerizable monomers, it is formed by 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. It is a method for producing a bolus, which is characterized by the fact that the bolus is manufactured.
<18> The method for producing a bolus according to any one of <15> to <17>, wherein the liquid material for forming a bolus contains a polymerization initiator.
<19> The method for producing a bolus according to <18>, wherein the polymerization initiator is either a thermal polymerization initiator or 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 producing a bolus of the above, it is possible to solve the above-mentioned problems in the past and achieve the above-mentioned object of the present invention.

30 Modeling device 31 Ink injection head unit for model body 32 Ink injection head unit for support body 33 UV irradiator 34 Model body support substrate 35 Stage 36 Smoothing member 37 Model body (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 Modeling object under construction (bolus: laser-cured part)
110 Mold for forming bolus 111 Bolus 112 Mold for forming bolus 113 Chest (breast)
114 Type that fits the chest surface 121 Male type for forming a 3D bolus for breasts 122 Female type for forming a 3D bolus for breasts 123 Gap when a male type and a female type are combined 124 3D bolus for breasts

Tokuhei 3-26994 Gazette Special Fair 6-47030 Gazette Japanese Patent No. 2999184 Japanese Unexamined Patent Publication No. 11-22192 Japanese Unexamined Patent Publication No. 3-115897

Claims (4)

A method for producing a bolus for producing a bolus composed of a hydrogel containing water, a polymer, and a mineral.
The bolus contains a hydrogel in which the water is contained in a three-dimensional network structure formed by combining the polymer and the mineral.
A bolus containing water, minerals, and a polymerizable monomer, which is formed by pouring a bolus-forming liquid material into a mold prepared by a three-dimensional printer based on the shape data of the patient's skin surface and curing the bolus. Manufacturing method. A method for producing a bolus for producing a bolus composed of a hydrogel containing water, a polymer, and a mineral.
The bolus contains a hydrogel in which the water is contained in a three-dimensional network structure formed by combining the polymer and the mineral.
An inkjet method in which a bolus-forming liquid material containing water, minerals, and a polymerizable monomer is ejected with an inkjet head based on the shape data of the patient's skin surface and the shape data of the affected part of the patient and cured with ultraviolet light. A method for manufacturing a bolus, which is characterized by being formed by a three-dimensional printer. A method for producing a bolus for producing a bolus composed of a hydrogel containing water, a polymer, and a mineral.
The bolus contains a hydrogel in which the water is contained in a three-dimensional network structure formed by combining the polymer and the mineral.
Using a liquid material for bolus formation containing water, minerals, and polymerizable monomers, it can be 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 area of the patient. A characteristic bolus manufacturing method. A bolus-forming liquid material used in the method for producing a bolus according to any one of claims 1 to 3.
A bolus-forming liquid material containing water, minerals, and polymerizable monomers.

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