TWI602594B - Reactant and system of treating biological tissue - Google Patents

Description

Treatment of biological tissue reactants and systems

The present invention relates to a method of treating biological tissue with a proton beam, and more particularly to a method of irradiating biological tissue with a proton beam generated by a synchrotron or a cyclotron.

In various countries of the world, various cancers have always been one of the main causes of human death. In addition to surgical removal of lesions, radiation therapy is also an important method for treating cancer.

Early radiotherapy mostly used photon knives (X-rays, gamma rays) to illuminate cancer cells, but in addition to harming cancer cells, photon knives can easily damage normal cells next to cancer cells, thus directing radioactive materials. Targeted treatment of specific targets was proposed, one of which was Boron Neutron Capture Therapy (BNCT).

Boron is a metalloid and the chemical symbol is represented by B. It is currently known that there are nine isotopes of boron, of which boron 10 ( ¹⁰ B) and boron 11 ( ¹¹ B) are stable. Boron 10 absorbs thermal neutrons and forms boron 11 transiently, and then alpha decays and releases alpha particles or gamma rays. Therefore, the reactant containing boron 10 is first attached to the target cancer cells and then irradiated with thermal neutrons. The reactants produce alpha particles or gamma rays and cause damage to cancer cells.

At present, the neutron source commonly used in the boron capture neutron method is divided into two types, one is to make a thermal neutron in a nuclear fission reactor or a proton generated by a reaction furnace to hit a target to generate thermal neutrons. The neutron beam generated by this method The flow rate is high and the effect is good, but it is very expensive, and the nuclear waste generated by nuclear fission is still difficult to solve until now; the other is that the synchrotron generates protons and the protons hit the special target to emit thermal neutrons. This method will not have nuclear waste. The problem, but the resulting neutron beam flow is not as good as the neutron beam produced by the nuclear splitting reactor.

In summary, when the neutron treatment, the neutron beam does not directly act on the target cancer cells, but scatters into the human body without direction. In addition to the limited effect, these neutron beams scattered into the human body will also be on the human body. This causes extra damage, so the present invention considers that there is a need for improvement in existing radiotherapy methods.

In order to enhance the effect of treating biological tissues with proton beams, the present invention proposes a new method.

In order to achieve the above object, the present invention provides a method for treating biological tissue using a proton beam, comprising the steps of: irradiating a proton beam with a biological tissue comprising a reactant, wherein the reactant comprises a first composite and a a second complex; the first complex reacts with more than one proton in the proton beam to release more than one neutron in the biological tissue; the second complex reacts with the neutron and is released in the biological tissue More than one alpha particle or one gamma ray is produced, and the alpha particle or the gamma ray acts on the biological tissue.

The present invention provides another method for treating biological tissue using a proton beam, comprising the steps of: providing a reactant, wherein the reactant comprises a first complex and a second complex; and introducing the reactant into a biological tissue And distributing the reactants in the biological tissue; irradiating the biological tissue with a proton beam to react the first complex with more than one proton in the proton beam to release more than one neutron in the biological tissue The second complex reacts with the neutron to release more than one alpha particle or a gamma ray in the biological tissue, and the alpha particle or the gamma ray has an effect on the biological tissue.

The present invention provides another method for treating biological tissue using a proton beam, comprising the steps of: irradiating a proton beam with a biological tissue comprising a reactant, wherein the reactant comprises a complex; the complex and the proton beam After more than one proton reaction, more than one alpha particle or a gamma ray is released in the biological tissue, and the alpha particle or the gamma ray has an effect on the biological tissue.

The present invention provides another method for treating biological tissue using a proton beam, comprising the steps of: providing a reactant, wherein the reactant comprises a complex; introducing the reactant into a biological tissue, and distributing the reactant Within the biological tissue; irradiating the biological tissue with a proton beam, and reacting the complex with more than one proton in the proton beam to release more than one alpha particle or a gamma ray in the biological tissue, the alpha particle or the Gamma rays have an effect on the biological tissue.

By irradiating the biological tissue with the proton beam according to the present invention, the biological tissue containing the reactant is irradiated with the proton beam to cause the reactant to release more than one alpha particle or a gamma ray, the alpha particle or the gamma ray to the living body The tissue acts to achieve the goal of completely preserving neutron energy and minimizing the impact on tissues outside the biological tissue.

The method for treating biological tissue by proton beam proposed by the present invention meets the requirements of biocompatibility of general radiotherapy without any additional impact on the human body.

1‧‧‧ Biological organization

2‧‧‧Reactants

3‧‧‧ catheter

4‧‧‧Proton beam

5‧‧‧ Illumination direction

201, 202, 203‧ ‧ steps

301, 302, 303‧ ‧ steps

Figure 1 is a schematic diagram of treatment of a target biological tissue using a proton beam; Figure 2 is a schematic diagram of a target biological tissue introduced into a body by a catheter; Figure 3 is a schematic diagram of a point scanning irradiation of a target biological tissue by a proton beam; A flow chart of a method for treating a target biological tissue using a proton beam according to an embodiment of the present invention.

Figure 5 is a flow chart of a method for treating a target biological tissue using a proton beam according to another embodiment of the present invention.

The present invention relates to a biological tissue containing a reactant by proton irradiation. The proton accelerates to obtain a suitable energy by a synchrotron or a cyclotron before illuminating the biological tissue, so that the proton can reach a certain depth in the biological tissue. The reactant generates one or more alpha particles or a gamma ray due to proton irradiation, and the alpha particle or the gamma ray acts on the biological tissue. How the synchrotron or the cyclotron accelerates the proton beam is well known to those skilled in the art and is not the focus of the present invention, and therefore will not be described again.

Please refer to FIG. 1 , which is a schematic diagram of processing biological tissue by proton beam in an embodiment of the present invention. As shown in Fig. 1, in the present embodiment, the reactant 2 is guided into the biological tissue 1 by the catheter 3. The manner of guiding is not limited to the use of a catheter, but also includes one of the methods of intramuscular injection, intravenous injection, oral administration or subcutaneous injection into the biological tissue. The intravenous injection method further includes one of a manner of intravenous addition, an intravenous drip method or a pressurized intravenous injection. Intravenous addition refers to the use of a syringe or other device to extract the reactants, and the patient is directly administered intravenously; intravenous drip refers to the rate of guiding the reactants into the vein by gravity or automatic device; intravenous intravenous injection Refers to manual or mechanical pressurization to stably introduce the reactants into the vein.

Next, the target biological tissue 1 containing the reactant is irradiated with the proton beam 4, the reactant 2 absorbs these protons entering in a certain direction and emits neutrons, and the released neutrons further react with the reactant 2 in the biological tissue 1 and The reactant 2 is caused to release alpha particles or gamma rays, and the alpha particles or gamma rays act on the target biological tissue 1, for example, to destroy cells of the biological tissue.

The reactant 2 of the present invention comprises a first complex and a second composite for the purpose of reacting the reactants 2 with protons, neutrons and finally releasing alpha particles or gamma rays. Wherein, the first complex absorbs protons and emits neutrons, and the second composite absorbs neutrons and emits alpha particles or gamma rays; in a preferred embodiment of the invention, the second composite is selected from boron compounds For example: BPA, BSH, BSH saccharide derivatives, GB-10, D-CDU, N5-2OH, H2DCP, DEQ-B, trimethyl hydrazine derivatives, aziridine derivatives, acridine, phenanthrene Pyridine, carbonyl polyamine, platinum (II)-amine complex, dibenzo, tribenzimidazole, glucose molecule, mannose molecule, ribose molecule, gulose molecule, fucose molecule, galactose molecule, maltose molecule , lactose molecule, phosphate, phosphate, phenylurea, thiourea, nitroimidazole, amine, benzamide, isocyanate, nicotinamide or hydrazine and other reactants containing boron 10, boron 10 is absorbing energy After less than 0.5 electron volts of thermal neutrons, boron 11 is formed transiently and alpha decay occurs simultaneously, while gamma rays are emitted. However, the present invention does not limit which material is selected for the second composite; and the characteristics of the second composite are first A compound is a substance that absorbs protons and emits thermal neutrons. Proton impact energy (Bombarding energy), the neutron generation rate (Neutron production rate), a target electrode m.p. (Target melting point), extreme heat capacity of the target (Target thermal conductivity), lithium ⁷ (7 Li) and beryllium ⁹ (9 Be) are It can meet the demand, in which lithium 7 ( ⁷ Li) is easier to obtain than 9 ( ⁹ Be ), and 铍 9 ( ⁹ Be ) is toxic and may have other effects on biological tissues, so it is better in the present invention. In the embodiment, lithium 7 ( ⁷ Li) is used as the first composite; in addition, it is obvious that the reactant 2 containing the first composite and the second composite is a mixture (or a compound); As shown in FIG. 2, when the target biological tissue 1 is in a human body, the present invention can guide the reactant 2 from the outside of the human body to the target biological tissue 1 in the human body by the catheter 3, wherein the catheter 3 can be a human body Externally inserted into the epidermal venous blood vessels and extending along the venous blood vessels to the target biological tissue 1 . In this manner, the reactant 2 can be distributed in the target biological tissue, and when the target biological tissue 1 is subsequently irradiated with the proton beam 4, the reactant 2 can be allowed to react with the proton inside the target biological tissue 1.

It should be noted that the reactant 2 of the present invention may also include only the second composite material composed of the boron-containing reactant described above, wherein the second composite absorbs protons and emits alpha particles or gamma rays.

Next, referring to FIG. 3, a schematic diagram of spot scanning of the target biological tissue 1 by the proton beam 4 according to an embodiment of the present invention. In order to illuminate the proton beam 4 irradiated from a certain direction on the target biological tissue 1, the present embodiment adopts the spot scanning irradiation as shown in FIG. 3; when performing the point scanning irradiation, the target biological tissue 1 is first The Z-axis direction is cut into a plurality of planes. Obviously, each cut plane layer is parallel to the X-axis and the Y-axis. The proton beam 4 is adjusted in intensity so that the depth of illumination is fixed on one of the plane layers, and then along X. The axis and the Y axis move, And presenting an illumination path such as an illumination direction 5, after a planar layer is completely irradiated, and then adjusting the intensity and irradiating the next planar layer; according to the above illumination mode, the present invention allows the proton beam 4 to be uniformly irradiated on each target tissue 1 In one place, but this is only a preferred embodiment of the irradiation of the proton beam 4, the present invention is not limited to the way in which the proton beam 4 irradiates the target biological tissue 1 in a passive scanning or an active scanning. Passive scanning increases the range of illumination by protons of different energies by scattering; then, in order to conform to the shape of the tumor, a second collimator is used for scattering, and finally the beam is adjusted to conform to the tumor with a compensator shape. Active scanning uses protons of different energies to regulate their sweep position with magnets for therapeutic purposes; there are two main ways of scanning: Continuous Scanning and Spot Scanning, both of which are mainly The difference is that there is no time interval between points and points of continuous scanning, while the interval scanning is a very short interval between points to scan. Additionally, the proton beam 4 of the present invention may be issued by a synchrotron or cyclotron.

As shown in FIG. 4, the present embodiment is a method for providing a reactant 2 and treating a target biological tissue containing the reactant 2 with a proton beam; the reactant 2 of the embodiment comprises a first composite and a second composite; Wherein, the first complex comprises, but is not limited to, lithium 7 ( ⁷ Li) or 铍 9 ( ⁹ Be); the second complex includes, but is not limited to, saccharide derivative of BPA, BSH, BSH containing boron 10 ( ¹⁰ B) , GB-10, D-CDU, N5-2OH, H2DCP, DEQ-B, trimethyl hydrazine derivative, aziridine derivative, acridine, phenanthridine, carbonyl polyamine, platinum (II)-amine Complex, dibenzo, tribenzimidazole, glucose molecule, mannose molecule, ribose molecule, gulose molecule, fucose molecule, galactose molecule, maltose molecule, lactose molecule, phosphate, phosphate, phenyl Reactants such as urea, thiourea, nitroimidazoles, amines, benzamides, isocyanates, nicotinamide or hydrazine. The steps of this embodiment are as follows:

Step 201: directing the reactant 2 to the target biological tissue 1, and distributing the reactant 2 in the target biological tissue 1, as shown in FIG. 1; the reactant 2 may be introduced into the target biological tissue through a catheter 3 1; As shown in Fig. 2, the catheter 3 can be introduced into the human body via a venous blood vessel and reach the target biological tissue 1 to guide the reactant 2 to the target biological tissue 1 in the human body.

Step 202: irradiating the target biological tissue 1 with the proton beam 4, as shown in FIG. 1, causing the first complex in the reactant 2 to absorb protons and release neutrons; wherein the proton beam 4 may be a synchrotron or a maneuver The accelerator emits a proton beam and illuminates the target biological tissue 1 in a passive or active scanning manner.

Step 203: the second complex in the reactant 2 is absorbed in the interior of the target biological tissue 1 by the first The neutrons released by the complex release alpha particles or gamma rays, and the alpha particles or gamma rays destroy the cellular structure in the target biological tissue 1.

Next, referring to FIG. 5, in another embodiment of the present invention, a method for providing a reactant 2 and treating a target biological tissue containing the reactant 2 by using a proton beam; the reactant 2 of the embodiment comprises a complex, The complex includes, but is not limited to, a boron derivative containing B10, BSH, BSH of boron 10 ( ¹⁰ B), GB-10, D-CDU, N5-2OH, H2DCP, DEQ-B, trimethylphosphonium derivative , aziridine derivative, acridine, phenanthridine, carbonyl polyamine, platinum (II)-amine complex, dibenzo, tribenzimidazole, glucose molecule, mannose molecule, ribose molecule, gulose molecule , fucose molecule, galactose molecule, maltose molecule, lactose molecule, phosphate, phosphate, phenylurea, thiourea, nitroimidazole, amine, benzamide, isocyanate, nicotinamide or hydrazine, etc. Reactant. The steps of this embodiment are as follows:

Step 302: directing the reactant 2 to the target biological tissue 1 and distributing the reactant 2 to the target biological tissue 1, as shown in Fig. 1; wherein the reactant 2 may be introduced to the target organism through a catheter 3 The tissue 1; as shown in Fig. 2, the catheter 3 can be accessed from outside the human body via a venous blood vessel to the target biological tissue 1 to guide the reactant 2 to the target biological tissue 1 in the human body.

Step 303: irradiating the target biological tissue 1 with the proton beam 4, as shown in Fig. 1, causing the complex in the reactant 2 to absorb protons and release the alpha particles or gamma rays to act on biological tissues, for example, destroying biological tissue cells; The proton beam 4 may be a proton beam emitted by a synchrotron or a cyclotron, and irradiated to the target biological tissue 1, which may be a passive or active scanning mode.

The target biological tissue 1 mentioned above may refer to various malignant tumors, and the cells in the target biological tissue 1 may refer to cancer cells. Therefore, the present invention may, but is not limited to, radiotherapy for cancer, and the target biological tissue 1 may also It is a biological tissue other than a malignant tumor.

The method of the present invention using the proton beam treatment of biological tissue, the reactants can be employed have been widely used two human boron-containing reactant, such as adding the boron reactant lithium ⁷ (7 Li).

As described above, the present invention provides a method for capturing protons by boron in biological tissues and releasing boron to release neutrons to affect biological tissues. The characteristics of this method can be called "promotion". Boron Proton induce Capture Therapy; BPiCT.

While the present invention has been described above in terms of the preferred embodiments thereof, it is not intended to limit the invention, and the invention may be modified and modified without departing from the spirit and scope of the invention. The scope of patent protection of the invention shall be subject to the patent application attached to this specification. The scope is defined.

201, 202, 203‧ ‧ steps

Claims (15)

A reactant for treating a biological tissue, after the reactant is introduced into the biological tissue, the biological tissue containing the reactant is subjected to a proton beam irradiation, and the reactant reacts with at least one proton in the proton beam in the biological tissue. At least one alpha particle or one gamma ray is released, and the at least one alpha particle or the gamma ray acts on the biological tissue. The reactant for treating a biological tissue according to claim 1, wherein the reactant comprises a first complex and a second complex, wherein the first complex reacts with the at least one proton after the biological tissue At least one neutron is released internally; the second complex reacts with the at least one neutron to release the at least one alpha particle or the gamma ray in the biological tissue. The reaction was treated biological tissue of the patent's scope of item 2, wherein the second complex contains boron ¹⁰ (10 B). The reactant for treating biological tissues according to claim 3, wherein the second complex is a carbohydrate derivative of BPA, BSH, BSH, GB-10, D-CDU, N5-2OH, H2DCP, DEQ -B, trimethyl hydrazine derivative, aziridine derivative, acridine, phenanthridine, carbonyl polyamine, platinum (II)-amine complex, dibenzo, tribenzimidazole, glucose molecule, mannose Molecules, ribose molecules, gulose molecules, fucose molecules, galactose molecules, maltose molecules, lactose molecules, phosphates, phosphates, phenylureas, thioureas, nitroimidazoles, amines, benzamides , isocyanate, nicotinamide or hydrazine. The reactant for treating biological tissue according to claim 2, wherein the first complex is lithium 7 ( ⁷ Li) or 铍 9 ( ⁹ Be ). The reactant for treating a biological tissue according to claim 1, wherein the proton beam is irradiated with the biological tissue by passive scanning or active scanning when the biological tissue containing the reactant is irradiated with the proton beam. The reaction was treated biological tissue in item 1 of the scope of patent applications, wherein the boron-containing reactant is ¹⁰ (10 B) consisting of a composite, the composite is of BPA, BSH, saccharide derivatives of BSH , GB-10, D-CDU, N5-2OH, H2DCP, DEQ-B, trimethyl hydrazine derivative, aziridine derivative, acridine, phenanthridine, carbonyl polyamine, platinum (II)-amine complex , dibenzo, tribenzimidazole, glucose molecule, mannose molecule, ribose molecule, gulose molecule, fucose molecule, galactose molecule, maltose molecule, lactose molecule, phosphate, phosphate, phenylurea And a thiourea, a nitroimidazole, an amine, a benzamide, an isocyanate, a nicotinamide or a hydrazine, the complex absorbing the at least one proton and releasing the at least one alpha particle or the gamma ray. A system for treating biological tissue, comprising a reactant introduced into the biological tissue; and a proton accelerator, the proton accelerator generating a proton beam; and the biological tissue containing the reactant is subjected to the proton beam irradiation, the reactant and At least one proton in the proton beam reacts to release at least one alpha particle or a gamma ray in the biological tissue, and the at least one alpha particle or the gamma ray has an effect on the biological tissue. The system for treating a biological tissue according to claim 8, wherein the reactant comprises a first complex and a second complex, wherein the first complex reacts with the at least one proton in the biological tissue Dissipating at least one neutron; the second complex reacts with the at least one neutron to release the at least one alpha particle or the gamma ray in the biological tissue. The system for processing biological tissue in item 9 of the patent application range, wherein the second complex contains boron ¹⁰ (10 B). The system for treating biological tissues according to claim 10, wherein the second complex is a carbohydrate derivative of BPA, BSH, BSH, GB-10, D-CDU, N5-2OH, H2DCP, DEQ- B, trimethyl hydrazine derivative, aziridine derivative, acridine, phenanthridine, carbonyl polyamine, platinum (II)-amine complex, dibenzo, tribenzimidazole, glucose molecule, mannose molecule , ribose molecule, gulose molecule, fucose molecule, galactose molecule, maltose molecule, lactose molecule, phosphate, phosphate, phenylurea, thiourea, nitroimidazole, amine, benzamide, Isocyanate, nicotinamide or hydrazine. The system for treating biological tissues according to claim 9, wherein the first complex is lithium 7 ( ⁷ Li) or 铍 9 ( ⁹ Be ). The system for treating biological tissues according to claim 8, wherein the proton beam is irradiated with the biological tissue by passive scanning or active scanning when the biological tissue is irradiated with the proton beam. The system for treating biological tissue according to claim 8, wherein the proton beam is obtained by a synchrotron or a cyclotron to obtain appropriate energy and then transferred to the biological tissue. The biological tissue processing system of item 8 of the patent application range, wherein the reactant is a boron-containing compound ¹⁰ (10 B) consisting of the composite is a saccharide derivative of BPA, BSH, BSH, and GB-10, D-CDU, N5-2OH, H2DCP, DEQ-B, trimethyl hydrazine derivative, aziridine derivative, acridine, phenanthridine, carbonyl polyamine, platinum (II)-amine complex , dibenzo, tribenzimidazole, glucose molecule, mannose molecule, ribose molecule, gulose molecule, fucose molecule, galactose molecule, maltose molecule, lactose molecule, phosphate, phosphate, phenylurea, Thiourea, nitroimidazole, amine, benzamide, isocyanate, nicotinamide or hydrazine, the complex will absorb the at least one proton and liberate the at least one alpha particle or the gamma ray.