A tissue compensator for radiotherapy and its preparation method

Abstract

This invention discloses a tissue compensator for radiotherapy and its preparation method, belonging to the field of medical devices. The radiotherapy tissue compensator comprises the following components by weight: 15-30 parts of hydrogen-containing silicone oil, 30-45 parts of vinyl silicone oil, 30-50 parts of silicone diluent, 2-3 parts of silicone tackifier, 1-5 parts of catalyst, and 0.3-2 parts of photosensitizer; the photosensitizer is polymer microspheres; the average particle size of the polymer microspheres is 3-8 μm; the refractive index of the polymer microspheres is 1.44-1.52; the refractive index parameter of the silicone system composed of hydrogen-containing silicone oil, vinyl silicone oil, silicone diluent, and silicone tackifier is 1.41-1.47; the refractive index parameter of the silicone system is equal to the weighted average of the refractive indices of the hydrogen-containing silicone oil, vinyl silicone oil, silicone diluent, and silicone tackifier. The radiotherapy tissue compensator provided by this invention possesses good transparency and can be effectively identified by the SGRT system.

Description

Technical Field

[0001] This application relates to the field of medical device technology, and more specifically, to a tissue compensator for radiotherapy and a method for preparing the same. Background Technology

[0002] Radiotherapy has become an important means of cancer treatment due to its significant efficacy and low side effects. However, due to the "build-up effect" of radiotherapy rays, it is often difficult to maximize the radiation dose to the lesion area when performing radiotherapy on superficial tumors. In this regard, tissue compensators are often used clinically to increase the build-up depth of the skin surface, thereby increasing the dose to the target area.

[0003] In recent years, surface-guided radiation therapy (SGRT) systems have been increasingly used in clinical practice as a supplement to image-guided radiotherapy due to their advantages such as zero radiation and real-time monitoring. Through optical surface positioning and tracking technology, patients can be positioned before treatment and their position tracked and monitored in real time during treatment, improving positioning speed and simplifying workflow. SGRT is finding increasing application in clinical radiotherapy practice.

[0004] To ensure clear visibility of the marking lines on the body surface and to confirm the proper integration of the compensator with the body surface contours, as well as the absence of cavities and air bubbles between the compensator and the body surface, currently used clinical compensators typically possess good transparency. However, such transparent compensators are often difficult to effectively identify in surface optical image-guided radiotherapy systems, thus limiting their application in these systems.

[0005] Therefore, there is an urgent need to develop a tissue compensator for radiotherapy that can be effectively identified by a radiotherapy system guided by optical images of the body surface. Summary of the Invention

[0006] The primary objective of this invention is to overcome the problem that existing transparent tissue compensators for radiotherapy are difficult to effectively identify in body surface optical image-guided radiotherapy systems, and to provide a tissue compensator for radiotherapy.

[0007] Another object of the present invention is to provide a method for preparing the above-mentioned tissue compensator for radiotherapy.

[0008] Another object of the present invention is to provide the application of the above-mentioned tissue compensator for radiotherapy in a body surface optical image-guided radiotherapy system.

[0009] To achieve the above objectives, the present invention employs the following technical solution: A tissue compensator for radiotherapy comprises the following components in parts by weight: 15-30 parts of hydrogen-containing silicone oil; 30-45 parts of vinyl silicone oil; 30-50 parts of silicon-containing diluent; 2-3 parts of silicone-containing tackifier; 1-5 parts catalyst; 0.3 to 2 parts of photosensitizer; The photosensitizer is a polymer microsphere; the average particle size of the polymer microsphere is 3~8μm; The refractive index of the polymer microspheres is 1.44~1.52; The refractive index parameter of the silicone system composed of hydrogen-containing silicone oil, vinyl silicone oil, silicone diluent, and silicone tackifier is 1.41~1.47. The refractive index parameter value of the silicone system is equal to the weighted average of the refractive indices of the hydrogen-containing silicone oil, the vinyl silicone oil, the silicone diluent, and the silicone tackifier.

[0010] In this invention, the "refractive index parameter value of the silicone system" is calculated according to the following formula (1-1):

[0011] Equation (1-1); Where m is the mass and n is the refractive index.

[0012] In this invention, the "refractive index" is obtained by testing with an Abbe refractometer.

[0013] The inventors discovered that by selecting polymer microspheres with specific refractive indices and average particle sizes as photosensors and adding them to radiotherapy tissue compensators, phase separation can occur within the continuous nonpolar silica phase while maintaining good transparency. This results in the formation of micro- and nano-scale aggregates, thereby constructing numerous scattering interfaces. When this radiotherapy tissue compensator is irradiated by a beam from an SGRT system, the beam undergoes repeated deflection and diffusion at the scattering interfaces, enhancing the light signal and enabling effective recognition by the SGRT system.

[0014] Preferably, the refractive index of the polymer microspheres is 1.46 to 1.50. More preferably, the refractive index of the polymer microspheres is 1.47 to 1.49.

[0015] The refractive index parameter of the silicone system affects the hardness and transparency of tissue compensators for radiotherapy. When the refractive index parameter of the silicone system is 1.41 to 1.47, the tissue compensator for radiotherapy has suitable transparency and hardness. More preferably, the refractive index parameter of the silicone system is 1.420 to 1.465. More preferably, the refractive index parameter of the silicone system is 1.443 to 1.461.

[0016] Preferably, the difference between the refractive index of the polymer microspheres and the refractive index parameter of the silicone system is ≤0.05. In this case, the tissue compensator for radiotherapy has better transparency.

[0017] In this invention, the difference between the refractive index of the polymer microspheres and the refractive index parameter value of the silicone system is equal to (the refractive index of the polymer microspheres) minus (the refractive index parameter value of the silicone system).

[0018] This invention uses "transmittance" to characterize the transparency of the radiotherapy tissue compensator. The transmittance is measured using a UV-Vis spectrophotometer; the higher the value, the higher the transparency.

[0019] In this invention, the "viscosity at 25°C" is measured using a glass capillary viscometer, and the test standard is GB / T265-1988.

[0020] Preferably, the average particle size of the polymer microspheres is 4~7μm.

[0021] More preferably, the average particle size of the polymer microspheres is 5~6 μm.

[0022] Preferably, the photosensitizer is polymethyl methacrylate microspheres.

[0023] Optionally, the weight of the photosensitizer is one or any two of the following: 1 part, 2 parts, 3 parts, 4 parts, 5 parts.

[0024] Preferably, the molar ratio of active hydrogen in the hydrogen-containing silicone oil to vinyl groups in the vinyl silicone oil is 1.2~1.5:1.

[0025] If vinyl groups remain in the tissue compensator used for radiotherapy, it can easily cause yellowing, thereby affecting the long-term stability of the product.

[0026] In this invention, there is no particular limitation on the type of hydrogen-containing silicone oil; any commonly used hydrogen-containing silicone oil in the art can be selected. Preferably, the hydrogen-containing silicone oil is a phenyl hydrogen-containing silicone oil.

[0027] Preferably, the hydrogen content of the hydrogen-containing silicone oil is 1~3 mmol / g, and the viscosity at 25°C is 200~1000 cs.

[0028] More preferably, the hydrogen-containing silicone oil has a hydrogen content of 1.2~1.6 mmol / g and a viscosity of 400~800 cs at 25°C.

[0029] Optionally, the weight parts of the hydrogen-containing silicone oil are one or any two of the following: 15 parts, 16 parts, 17 parts, 18 parts, 19 parts, 20 parts, 21 parts, 22 parts, 23 parts, 24 parts, 25 parts, 26 parts, 27 parts, 28 parts, 29 parts, and 30 parts.

[0030] In this invention, there is no particular limitation on the type of vinyl silicone oil; any vinyl silicone oil commonly used in the art can be selected. Preferably, the vinyl silicone oil is a phenyl vinyl silicone oil.

[0031] Preferably, the vinyl silicone oil has a vinyl content of 0.5~1 mmol / g and a viscosity of 200~1000 cs at 25°C.

[0032] More preferably, the vinyl silicone oil has a vinyl content of 0.6~0.8 mmol / g and a viscosity of 400~800 cs at 25°C.

[0033] Optionally, the vinyl silicone oil is in the range of one or any two of the following weight parts: 30 parts, 31 parts, 32 parts, 33 parts, 34 parts, 35 parts, 36 parts, 37 parts, 38 parts, 39 parts, 40 parts, 41 parts, 42 parts, 43 parts, 44 parts, and 45 parts.

[0034] Preferably, the silicon-containing diluent is dimethyl silicone oil.

[0035] More preferably, the silicon-containing diluent is dimethyl silicone oil with a viscosity of 20-50 cs at 25°C.

[0036] Optionally, the weight parts of the silicon-containing diluent are one or any two of the following: 30 parts, 31 parts, 32 parts, 33 parts, 34 parts, 35 parts, 36 parts, 37 parts, 38 parts, 39 parts, 40 parts, 41 parts, 42 parts, 43 parts, 44 parts, 45 parts, 46 parts, 47 parts, 48 ​​parts, 49 parts, and 50 parts.

[0037] Preferably, the silicone-containing tackifier is one or more of MQ silicone resin or boron silicone tackifier.

[0038] More preferably, the silicone-containing tackifier is MQ silicone resin.

[0039] MQ silicone resin is composed of tetrafunctional siloxane units (SiO2). 4 / 2 Organosilicon compounds containing monofunctional siloxane units (R3SiO) and Q) 1 / 2 The silicone resin (MQ) is a three-dimensional spherical silicone ester produced by co-hydrolysis-condensation polymerization of organosilicon compounds. The organic portion of the MQ silicone resin improves its compatibility with the radiotherapy tissue compensator, acting as an adhesive. The siloxane chains enhance the mechanical strength, cohesive strength, and peel strength of the radiotherapy tissue compensator, providing reinforcement.

[0040] More preferably, the silicone-containing tackifier is phenyl vinyl MQ silicone resin.

[0041] The phenyl vinyl MQ silicone resin can also undergo a hydrosilylation reaction with hydrogen-containing silicone oil to further form a cross-linked structure, thereby improving the mechanical strength, cohesive strength, and peel strength of the tissue compensator for radiotherapy.

[0042] Most preferably, the silicone-containing tackifier is a phenyl vinyl MQ silicone resin with a number average molecular weight of 2800-3500, an M / Q ratio of 0.7-0.8, and a vinyl content of 1.0-1.4%.

[0043] In this invention, the catalyst can be any catalyst well-known to those skilled in the art capable of causing a hydrosilylation reaction between hydrogen-containing silicone oil and vinyl silicone oil, such as one or more of chloroplatinic acid, castor catalyst, or platinum catalyst. Preferably, the catalyst is a castor catalyst.

[0044] Optionally, the catalyst may be in the range of one, two, three, four, or five parts by weight, or any two of these ranges.

[0045] The method for preparing the above-mentioned tissue compensator for radiotherapy is also within the scope of protection of this invention, and includes the following steps: After mixing all the raw materials evenly, the mixture is poured into a mold and reacted at room temperature for 2-6 hours. Then, the mixture is heated to react, cooled, and demolded to obtain the tissue compensator for radiotherapy.

[0046] In the preparation method of the tissue compensator for radiotherapy, the raw materials react at room temperature for a period of time to complete the initial polymerization and solidification, so as to prevent the reaction from being too violent and producing "explosive polymerization" when heated later.

[0047] In this invention, the room temperature has a technical meaning known in the art, generally referring to 20-30°C.

[0048] Preferably, the temperature of the heating reaction is 50~80℃.

[0049] Preferably, the heating reaction time is 4 to 8 hours.

[0050] Preferably, the mold has dimensions of 300mm × 300mm × 5mm.

[0051] The application of the aforementioned tissue compensators for radiotherapy in surface optical image-guided radiotherapy systems is also within the scope of protection of this invention.

[0052] Compared with the prior art, the beneficial effects of the present invention include: This invention selects polymer microspheres with specific refractive index and average particle size as photosensitizers and adds them to tissue compensators for radiotherapy, so that the tissue compensators for radiotherapy can be effectively recognized by the SGRT system while maintaining transparency.

[0053] In addition, the tissue compensator for radiotherapy provided by this invention also has good softness, skin-friendliness, and adhesion. Attached Figure Description

[0054] Figure 1 This is an appearance diagram of the tissue compensator for radiotherapy prepared in Example 2 of the present invention.

[0055] Figure 2 This is a diagram showing the SGRT system recognition effect of the tissue compensator for radiotherapy prepared in Example 2 of the present invention.

[0056] Figure 3 This is a diagram showing the SGRT system recognition effect of the tissue compensator for radiotherapy prepared in Comparative Example 3 of the present invention. Detailed Implementation

[0057] The present invention will be further described below with reference to embodiments and comparative examples. These embodiments are merely typical descriptions of the present invention, but the present invention is not limited thereto. Unless otherwise specified, the test methods used in the following embodiments and comparative examples are conventional methods, and the raw materials and reagents used are commercially available from conventional commercial sources.

[0058] Information on the raw materials used in each embodiment and comparative example is shown in Table 1.

[0059] Table 1 Raw Material Information Table

[0060] The refractive index of each raw material was measured using an Abbe refractometer, and the results are shown below: Hydrogen-containing silicone oil: refractive index 1.494; Vinyl silicone oil #1: Refractive index 1.476; Vinyl silicone oil #2: Refractive index 1.402; Silicon-containing diluent: refractive index 1.403; Silicon-containing tackifier: refractive index 1.515; Photosensitive agent #1: Refractive index 1.482; Photosensitive agent #2: Refractive index 1.597; Photosensitive agent #3: Refractive index 2.743; Photosensitive agent #4: Refractive index 1.482; Photosensitive agent #5: Refractive index 1.482.

[0061] The same reagents were used in the parallel experiments of all embodiments and comparative examples in this invention.

[0062] In Examples 1-3 and Comparative Examples 1-9, the tissue compensator for radiotherapy was prepared by the following method, including the following steps: According to the formula in Table 2, after mixing all the raw materials evenly, the mixture is poured into a mold with a size of 300mm×300mm×5mm, reacted at room temperature for 3 hours, then heated to 60℃ for 6 hours, cooled and demolded to obtain the tissue compensator for radiotherapy.

[0063] The specific formulations of each embodiment and comparative example are shown in Table 2.

[0064] Table 2. Specific formulations for each embodiment and comparative example (unit: g)

[0065] The refractive index parameter values ​​of the silicone system in the table are calculated according to formula (1-1) in the instruction manual.

[0066] Performance testing and characterization (1) Hardness test At 23±2℃, the hardness of the radiotherapy tissue compensators prepared in each embodiment and comparative example was tested using a Shore hardness tester. The test results are shown in Table 3.

[0067] (2) Light transmittance test The transmittance of the radiotherapy tissue compensators prepared in each embodiment and comparative example was tested at a wavelength of 550 nm using a UV-Vis spectrophotometer. The test results are shown in Table 3.

[0068] (3) SGRT system recognition test Point cloud images of the area covered by the tissue compensator (Bolus) were acquired using the ACCUTRAK SGRT system. If the acquired point cloud image is clear and complete without local missing parts, has uniform point cloud density without misalignment or gaps, and the noise points are within the ideal range (i.e., more than 90% of the target area is uniformly sampled, and the difference between the maximum and minimum density is ≤30%), it is determined that it can be effectively identified by the SGRT system. The test results are shown in Table 3.

[0069] Table 3. Test results of the tissue compensators for radiotherapy prepared in each embodiment and comparative example.

[0070] As shown in Table 3, the tissue compensator for radiotherapy provided by this invention has good transparency, with a transmittance of over 19%, and all of it can be effectively identified by the SGRT system. Comparing Examples 1-4, it can be seen that when the difference between the refractive index of the polymer microspheres and the refractive index parameter of the silicone system is ≤0.05, the prepared tissue compensator for radiotherapy has better transparency, with a transmittance of over 23%.

[0071] Comparing Example 2, Comparative Example 1, and Comparative Example 2, it can be seen that when no photosensitizer is added, the transmittance of the radiotherapy tissue compensator is the highest, reaching 32.65%, but it cannot be recognized by the SGRT system due to the lack of a scattering interface. When the amount of photosensitizer added is 0.1 parts, the amount of photosensitizer is insufficient to form a scattering interface with sufficient scattering intensity, and it still cannot be effectively recognized by the SGRT system. When the amount of photosensitizer added is increased to 0.3 parts, a scattering interface with sufficient scattering intensity can be formed, and it can be successfully recognized by the SGRT system.

[0072] Comparing Examples 2, 3, and 4, it is evident that when titanium dioxide is selected as the photosensitizer, the transmittance of the tissue compensator for radiotherapy decreases significantly. Although increasing the amount of titanium dioxide can create a sufficient scattering interface, thereby enabling effective recognition by the SGRT system, the transmittance of the tissue compensator for radiotherapy is only 0.32%, and the hardness reaches 17, which fails to meet the application requirements.

[0073] Comparative Examples 2 and 5-7 show that when polystyrene microspheres are selected as the photosensitizer, although increasing the amount of polystyrene microspheres can form a sufficient scattering interface to achieve effective recognition by the SGRT system, the transmittance of the tissue compensator for radiotherapy is only 5.41% and the hardness is as high as 43, which cannot meet the application requirements.

[0074] Comparative Examples 2 and 8-9 show that when the average particle size of the polymethyl methacrylate (PMMA) microspheres is outside the specified range, they cannot be effectively identified by the SGRT system. This is because when the average particle size of the PMMA microspheres is too small, they are prone to aggregation and cannot form a uniform micro / nano-scale scattering interface. Conversely, when the average particle size of the PMMA microspheres is too large, geometric optical scattering of light easily occurs, leading to significant light deflection or even reflection, resulting in uneven light distribution, which is also difficult for the SGRT system to reliably identify.

[0075] The specific embodiments of the present invention have been described above. It should be understood that the present invention is not limited to the specific embodiments described above, and those skilled in the art can make various modifications or variations within the scope of the claims, which do not affect the essence of the present invention.

Claims

1. A tissue compensator for radiotherapy, characterized in that, Includes the following components by weight: 15-30 parts of hydrogen-containing silicone oil; 30-45 parts of vinyl silicone oil; 30-50 parts of silicon-containing diluent; 2-3 parts of silicone-containing tackifier; 1-5 parts catalyst; 0.3 to 2 parts of photosensitizer; The photosensitizer is a polymer microsphere; the average particle size of the polymer microsphere is 3~8μm; The refractive index of the polymer microspheres is 1.44~1.52; The refractive index parameter of the silicone system composed of hydrogen-containing silicone oil, vinyl silicone oil, silicone-containing diluent, and silicone-containing tackifier is 1.41~1.

47. The refractive index parameter value of the silicone system is equal to the weighted average of the refractive indices of the hydrogen-containing silicone oil, the vinyl silicone oil, the silicone diluent, and the silicone tackifier. The refractive index parameter of the silicone system is calculated according to the following formula (1-1): Equation (1-1).

2. The tissue compensator for radiotherapy according to claim 1, characterized in that, The polymer microspheres have a refractive index of 1.46 to 1.

50.

3. The tissue compensator for radiotherapy according to claim 1, characterized in that, The refractive index parameter of the silicone system is 1.420~1.

465.

4. The tissue compensator for radiotherapy according to claim 1, characterized in that, The difference between the refractive index of the polymer microspheres and the refractive index parameter of the silica gel system is ≤0.

05.

5. The tissue compensator for radiotherapy according to claim 1, characterized in that, The average particle size of the polymer microspheres is 4~7μm.

6. The tissue compensator for radiotherapy according to claim 1, characterized in that, The photosensitizer is polymethyl methacrylate microspheres.

7. The tissue compensator for radiotherapy according to claim 1, characterized in that, The molar ratio of active hydrogen in the hydrogen-containing silicone oil to vinyl groups in the vinyl silicone oil is 1.2~1.5:

1.

8. A method for preparing the tissue compensator for radiotherapy according to any one of claims 1 to 7, characterized in that, Includes the following steps: After mixing all the raw materials evenly, the mixture is poured into a mold and reacted at room temperature for 2-6 hours. Then, the mixture is heated to react, cooled, and demolded to obtain the tissue compensator for radiotherapy.

9. The preparation method according to claim 8, characterized in that, The temperature of the heating reaction is 50~80℃.

10. The use of the tissue compensator for radiotherapy as described in any one of claims 1 to 7 in a surface optical image-guided radiotherapy system.

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