Device for tumor radiotherapy and preparation method

Abstract

The invention relates to a device for tumor radiotherapy, which is particularly used for isolating tumor tissues from normal tissues in tumor radiotherapy, and comprises an external material made of an absorbable polymer fiber membrane and dry hydrogel filled in the external material, the mechanical property of the device is controlled by the volume ratio of the dry hydrogel filled in the external material. According to the invention, the mechanical property of the whole bag material is changed by utilizing the different volume proportions of the dry hydrogel filling bag, so that the device for tumor radiotherapy is designed. The multi-layer structural design realizes all-around protection of normal tissues, provides structural support, designs the surface layer to ensure attachment, and maximizes radiation absorption of the inner layer. According to the device provided by the invention, a stable isolation space can be established, and the irradiation dose to other adjacent tissues is reduced.

Description

Technical Field

[0001] The present invention relates to the technical field of medical polymer materials, and in particular to a device for tumor radiotherapy and a preparation method thereof, which are mainly used for tumor radiotherapy protection. Background Art

[0002] Radiotherapy is a method of treating malignant tumors using high-energy radiation. It achieves the therapeutic purpose by destroying the DNA of tumor cells and preventing their proliferation and growth. In radiotherapy, accurately focusing the radiation dose on the tumor while minimizing exposure to surrounding normal tissue is the key to improving treatment efficacy and patient safety. To achieve this goal, modern radiotherapy technology is committed to creating a sharply changing dose gradient at the junction of tumor and normal tissue. The steep drop in this dose gradient means that the radiation dose from the tumor area to normal tissue can be quickly reduced, thereby effectively protecting normal tissue from damage. In order to protect the surrounding normal tissue while treating the tumor, researchers have explored a new strategy: setting up a physical barrier between the tumor organ and the normal organ. This barrier can effectively block radiation and reduce the radiation dose received by normal tissue.

[0003] In clinical practice, various types of injectable hydrogels have been widely studied and applied in the medical field. In particular, polyethylene glycol (PEG), due to its unique physical and chemical properties, is used as an isolation material in tumor radiotherapy to protect surrounding normal tissues from radiation damage. However, PEG-based hydrogels have certain technical challenges in practical applications. In a study involving 258 patients, 1.6% (i.e., 4 cases) of patients suffered complications of rectal wall penetration. This suggests that special attention needs to be paid to avoid damage to adjacent tissues during injection. In addition, the preparation and injection process of PEG hydrogels is relatively cumbersome. During the operation, polyethylene glycol needs to be mixed with a dilute solution of trilysine through a Y-type connector to induce a cross-linking reaction. This mixed liquid needs to be injected quickly and polymerized in situ into a soft gel in about 10 seconds. If any unexpected situation is encountered during the injection process, resulting in interruption of the injection, equipment blockage may occur, which requires the operator to prepare a backup system to deal with it. This process is not only complicated to operate, but also has high requirements on the operator's technical level and adaptability.

[0004] In cervical cancer, intracavitary radiotherapy is an important treatment method in radical radiotherapy, and the standard method to reduce the rectal dose is gauze filling. However, during the treatment process, the position of the gauze may shift due to changes in the patient's body position or intestinal peristalsis, and the gauze may absorb intestinal secretions, increase the volume, and thus affect its isolation effect. At present, 3D printed tissue fillers are also used as physical barriers between tumor organs and normal organs, but the current tissue fillers have disadvantages in mechanical properties, surface characteristics, stress distribution, etc. For example, the incoordination of the mechanical properties such as elastic modulus, hardness, and compressive strength of the printed tissue fillers leads to incoordination and non-fitting between the fillers and the surrounding tissues, and even tissue fillers can cause damage to the body tissues. Tissue fillers may also cause uneven stress distribution at the interface, and the concentration of local stress can easily lead to tissue damage or displacement of the filler. In addition, under continuous or periodic loads (such as squeezing between organs), tissue fillers may deform or rupture, thus failing to achieve the purpose of isolation.

[0005] Patent document with publication number CN 103961805A discloses a tissue equivalent filler for cancer radiotherapy, which is prepared by mixing liquid paraffin and styrene-ethylene-butadiene block copolymer to obtain a mixture, and then heating and curing the mixture to obtain the tissue equivalent filler. Although the filler can increase the compatibility with the patient's skin, it can only be used for isolating the skin surface, and cannot be used for isolating tumor tissue from adjacent normal tissue. Furthermore, the mechanical properties of the filler when the patient changes position or other activities are not considered, and the filler may denature or rupture during operation, thereby resulting in uneven distribution of the emission dose.

[0006] In addition, on the one hand, there are differences in understanding among those skilled in the art; on the other hand, the applicant studied a large number of documents and patents when making the present invention, but due to space limitations, not all details and contents are listed in detail. However, this does not mean that the present invention does not have the characteristics of these prior arts. On the contrary, the present invention already has all the characteristics of the prior art, and the applicant reserves the right to add relevant prior art to the background technology. Summary of the invention

[0007] In view of the shortcomings of the prior art, the present invention provides a device for tumor radiotherapy, which is particularly used for isolating tumor tissue and normal tissue during tumor radiotherapy, and comprises: an external material made of an absorbable polymer fiber membrane and a dry hydrogel filled in the external material. The mechanical properties of the device are controlled by the volume ratio of the dry hydrogel filled in the external material.

[0008] According to a preferred embodiment, the volume proportion of the dry hydrogel filled in the external material is 5% to 100%, preferably 10% to 80%.

[0009] According to a preferred embodiment, the device includes a surface bag with a lower Young's modulus that contacts human tissue and / or organs, formed by filling an external material with a second filling volume of dry hydrogel, and a core bag with a greater radiation absorption rate or radiation absorption dose, formed by filling an external material with a third filling volume of dry hydrogel.

[0010] According to a preferred embodiment, the device further comprises: a skeleton bag with a higher Young's modulus formed by filling the dry hydrogel into an external material at a first filling volume.

[0011] According to a preferred embodiment, the first filling volume of the dry hydrogel is smaller than the second filling volume, and the second filling volume is smaller than the third filling volume. The first filling volume is preferably 5-10%. The second filling volume is preferably 20-60%. The third filling volume is preferably 80-100%.

[0012] According to a preferred embodiment, the volume ratio of the dry hydrogel filled in the external material can control the ability of the device to resist deformation.

[0013] The second aspect of the present invention provides a multi-layer stacked device for tumor radiotherapy, comprising: a surface bag with a lower Young's modulus that contacts human tissue and / or organs formed by filling the dry hydrogel provided by the first aspect of the present invention with a second filling volume into an external material, and a core bag with a greater radiation absorption rate or radiation absorption dose formed by filling the dry hydrogel with a third filling volume into an external material, wherein the core bag is the central layer, and the surface bags are respectively covered from the central layer to the upper and lower layers, thereby forming a multi-layer stacked device for isolating tumor tissue and normal tissue in tumor radiotherapy.

[0014] According to a preferred embodiment, the device further comprises: a skeleton bag with a higher Young's modulus formed by filling the dry hydrogel into an external material at a first filling volume.

[0015] A skeleton bag is preferably included between the core bag and the surface bag.

[0016] According to a preferred embodiment, the first filling volume of the dry hydrogel is smaller than the second filling volume, and the second filling volume is smaller than the third filling volume. The first filling volume is preferably 5-10%. The second filling volume is preferably 20-60%. The third filling volume is preferably 80-100%.

[0017] The third aspect of the present invention provides a multi-layer wrapped device for tumor radiotherapy, comprising: a surface bag with a lower Young's modulus that contacts human tissue and / or organs, formed by filling the dry hydrogel provided by the first aspect of the present invention with a second filling volume in an external material, and a core bag with a greater radiation absorption rate or radiation absorption dose, formed by filling the dry hydrogel with a third filling volume in an external material, wherein the core bag is the central layer, and the surface bags are respectively wrapped from the central layer to the outside, thereby forming a multi-layer wrapped device for isolating tumor tissue and normal tissue in tumor radiotherapy.

[0018] According to a preferred embodiment, the device further comprises: a skeleton bag with a higher Young's modulus formed by filling the dry hydrogel into an external material at a first filling volume.

[0019] A skeleton bag is preferably included between the core bag and the surface bag.

[0020] According to a preferred embodiment, the first filling volume of the dry hydrogel is smaller than the second filling volume, and the second filling volume is smaller than the third filling volume. The first filling volume is preferably 5-10%. The second filling volume is preferably 20-60%. The third filling volume is preferably 80-100%.

[0021] The fourth aspect of the present invention provides a frame-type device for tumor radiotherapy, comprising: a surface bag with a lower Young's modulus that contacts human tissue and / or organs formed by filling the dry hydrogel provided by the first aspect of the present invention with a second filling volume in an external material, and a core bag with a greater radiation absorption rate or radiation absorption dose formed by filling the dry hydrogel with a third filling volume in an external material, wherein the surface bag is draped over an outer contour frame to form a closed structure, and the core bag is filled inside the closed structure, thereby forming a frame-type device for isolating tumor tissue and normal tissue in tumor radiotherapy.

[0022] According to a preferred embodiment, the device further comprises: a skeleton bag with a higher Young's modulus formed by filling the dry hydrogel into an external material at a first filling volume.

[0023] According to a preferred embodiment, the skeleton bag forms an outer contour frame member to protect normal tissue in a frame-covering manner.

[0024] According to a preferred embodiment, the first filling volume of the dry hydrogel is smaller than the second filling volume, and the second filling volume is smaller than the third filling volume. The first filling volume is preferably 5-10%. The second filling volume is preferably 20-60%. The third filling volume is preferably 80-100%.

[0025] The fifth aspect of the present invention provides a hemispherical device for tumor radiotherapy, comprising: a surface bag with a lower Young's modulus that contacts human tissue and / or organs formed by filling the dry hydrogel provided by the first aspect of the present invention with a second filling volume into an external material, and a core bag with a greater radiation absorption rate or radiation absorption dose formed by filling the dry hydrogel with a third filling volume into an external material, wherein the surface bag is used to form a hemispherical outer shell surface to abut against normal tissue / or organs, and the core bag is used to form a hemispherical base surface to absorb radiation, thereby forming a hemispherical device for isolating tumor tissue and normal tissue in tumor radiotherapy.

[0026] According to a preferred embodiment, the device further comprises: a skeleton bag with a higher Young's modulus formed by filling the dry hydrogel into an external material at a first filling volume.

[0027] According to a preferred embodiment, a skeleton bag is provided between the hemispherical shell and the base surface to form a canine-tooth occlusion.

[0028] According to a preferred embodiment, the first filling volume of the dry hydrogel is smaller than the second filling volume, and the second filling volume is smaller than the third filling volume. The first filling volume is preferably 5-10%. The second filling volume is preferably 20-60%. The third filling volume is preferably 80-100%.

[0029] The sixth aspect of the present invention provides a strip-shaped device for tumor radiotherapy, comprising: a surface pouch with a lower Young's modulus in contact with human tissue and / or organs formed by filling the dry hydrogel provided in the first aspect of the present invention with a second filling volume into an external material, and a core pouch with a greater radiation absorption rate or radiation absorption dose formed by filling the dry hydrogel with a third filling volume into an external material, wherein the core pouch is taken as the center and the surface pouch is wrapped from the center to the outside to form a strip-shaped device for isolating tumor tissue and normal tissue in tumor radiotherapy.

[0030] According to a preferred embodiment, the device further comprises: a skeleton bag with a higher Young's modulus formed by filling the dry hydrogel into an external material at a first filling volume.

[0031] A skeleton bag is preferably included between the core bag and the surface bag.

[0032] According to a preferred embodiment, the first filling volume of the dry hydrogel is smaller than the second filling volume, and the second filling volume is smaller than the third filling volume. The first filling volume is preferably 5-10%. The second filling volume is preferably 20-60%. The third filling volume is preferably 80-100%.

[0033] The strip-shaped capsule can be used to isolate head and neck tumors, such as blood vessels and nerves in the neck. In the treatment of oral cancer or other maxillofacial tumors, the strip-shaped capsule can be used to isolate tumor tissue and normal tissue to protect important structures and functions. In the treatment of brain tumors or other neurological diseases, the hydrogel strip may be used to isolate and protect important neural structures.

[0034] A seventh aspect of the present invention provides a hydrogel composition, which comprises a pouch made of an absorbable polymer fiber membrane and a dry hydrogel filled in the pouch, wherein the mechanical properties of the hydrogel composition are controlled by the volume ratio of the dry hydrogel filled in the pouch.

[0035] According to a preferred embodiment, the bag made of absorbable polymer fiber membrane is composed of one or more of polyethylene glycol acid, hexafluoroisopropanol, polylactic acid, polydioxanone, polycaprolactone, polylactic acid-polyethylene glycol acid copolymer, and poly L-lactic acid-ε-caprolactone.

[0036] An eighth aspect of the present invention provides a method for preparing a device for tumor radiotherapy, comprising the following steps:

[0037] The absorbable polymer fiber membrane is prepared by 3D printing or electrospinning technology.

[0038] Obtaining a dry hydrogel by one or more methods selected from freeze drying, room temperature drying, solvent replacement, vacuum drying or supercritical drying;

[0039] The dry hydrogel is filled into a capsule made of an absorbable polymer fiber membrane according to a specific volume ratio to form a device for tumor radiotherapy.

[0040] According to a preferred embodiment, the volume proportion of the dry hydrogel filled in the external material is 5% to 100%, preferably 10% to 80%.

[0041] The ninth aspect of the present invention provides the use of the device provided by the first to sixth aspects of the present invention, the hydrogel composition provided by the seventh aspect of the present invention, and the preparation method provided by the eighth aspect of the present invention in tumor radiotherapy protection.

[0042] The tenth aspect of the present invention provides the use of the device provided by the first to sixth aspects of the present invention, the hydrogel composition provided by the seventh aspect of the present invention, and the preparation method provided by the eighth aspect of the present invention in interventional surgery.

[0043] The present invention utilizes the different volume proportions of the dry hydrogel filled in the capsule to change the mechanical properties of the overall capsule material and designs a device for tumor radiotherapy. Unexpectedly, the present invention finds that the Young's modulus of the dry hydrogel filled in the capsule with the second filling volume is smaller than the Young's modulus of the capsule filled with the first filling volume. This phenomenon may be related to the interaction between the external material made of the absorbable polymer fiber membrane and the dry hydrogel filled in the external material. The interface bonding between the dry hydrogel and the fiber membrane can be achieved by physical adsorption or chemical cross-linking. The dry hydrogel and the fiber membrane contain reactive functional groups, and the two may react chemically at the interface, thereby increasing the structural integrity and mechanical properties of the composite material. The combination of the dry hydrogel and the fiber membrane can increase the stability of the composite material. Under the first filling volume condition, the dry hydrogel forms a good interface bonding with the fiber membrane after rehydration, thereby improving the overall strength of the material. At this time, the overall Young's modulus of the capsule is higher, the rigidity is larger, the capsule is not easy to deform, and has better support characteristics. Therefore, the structure formed when the proportion of the volume of the pouch filled with dry hydrogel is low is used as a skeleton pouch, which can form an outer contour frame to protect healthy tissue. Second, when the proportion of the volume of the pouch filled with dry hydrogel gradually increases, such as 20%, the Young's modulus is small, and the overall properties of the pouch are gradually affected by the dry hydrogel, and its rigidity is low. Specifically, materials with low Young's modulus are easier to integrate with human soft tissue because they have similar mechanical properties, thereby reducing the mechanical mismatch with surrounding tissues. The pouch material with low Young's modulus can provide better comfort. Therefore, the pouch under this filling condition is used as the outermost layer (directly in contact with human tissue or organs) because it can better adapt to the natural shape and movement of the body, especially the changes in body position and the activities of the organs themselves (such as gastrointestinal peristalsis). The pouch material with low Young's modulus changes in accordance with the changes in organ or tissue activities, has a higher degree of flexibility, and is not easy to cause additional damage to the body. Because tumor tissue undergoes radiotherapy, it may produce inflammatory reactions, acute and chronic pain and other symptoms, and the tumor site is more sensitive. If the outer surface of the capsule used to isolate the tumor tissue and adjacent healthy tissue is more rigid, the patient is more likely to feel uncomfortable when moving or changing position. In addition, as the outermost layer of the capsule, it is easy to conform to the tissue structure to form a fitting protective wall, and it is not easy to shift even if the body moves. Because of its low filling rate and limited water absorption, it causes little damage to the tissue. Third, when the volume of the dry hydrogel-filled capsule increases to 80%, the Young's modulus increases and has a certain rigidity. As the core, it can maintain the specific shape and position of the overall device when absorbing water. At the same time, the 80% filling rate can absorb as much radiation as possible, further reducing damage to normal tissues.

[0044] Therefore, the device provided by the present invention can establish a stable isolation space (spacer) to reduce the radiation dose to other adjacent tissues. In this way, doctors can apply a single large dose of radiation therapy to the tumor without worrying about causing excessive damage to adjacent normal tissues. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] Figure 1 It is a granular dry hydrogel containing iodine;

[0046] Figure 2 It is a PLGA capsule;

[0047] Figure 3 It is a PLGA bag encapsulating iodine-containing granular dry hydrogel;

[0048] Figure 4 This is the CT imaging result of the capsular bag;

[0049] Figure 5 Comparison of cell status under different concentrations of iodine-containing capsule extracts;

[0050] Figure 6 is the cell survival rate under different concentrations of iodine capsule extract;

[0051] Figure 7 It is a powdered dry hydrogel containing HAp;

[0052] Figure 8 This is the CT imaging result of the capsular bag;

[0053] Fig. 9 Comparison of cell status under different extract concentrations of HAp-containing capsules;

[0054] Fig.10 is the cell survival rate under different concentrations of extracts containing HAp capsules;

[0055] Fig.11 The appearance of the pouch (after rehydration) corresponding to different dry hydrogel filling volumes;

[0056] Fig.12 is the Young's modulus corresponding to different dry hydrogel filling rates;

[0057] Fig.13 A side view of a multi-layer stacked device;

[0058] Fig.14 It is a structural diagram of a multi-layer wrapped device;

[0059] Fig.15 It is a structural diagram of a frame-type device;

[0060] Fig.16 This is a disassembled diagram of a frame-type device;

[0061] Fig.17 It is a structural diagram of a hemispherical device;

[0062] Fig.18 This is a disassembled diagram of the hemispherical device;

[0063] Fig.19 This is a disassembly diagram of the hemispherical device from another perspective;

[0064] Fig. 20 It is a structural diagram of a device in the form of a strip.

[0065] Reference numerals list

[0066] 100: pouch; 110: core pouch; 120: skeleton pouch; 130: surface pouch; 200: dry hydrogel. DETAILED DESCRIPTION

[0067] The following is a detailed description with reference to the accompanying drawings.

[0068] Main consumables and reagents: polylactic acid-polyethylene glycol acid copolymer (PLGA, 75:25, 1.0±0.2dL / g, Sichuan Dikang Technology Pharmaceutical Co., Ltd.); 1,1,1,3,3,3-hexafluoroisopropanol (HFIP); iohexol; poly (L-lactic acid-ε-caprolactone) (PLCL); hydroxyapatite (HAp, 25-40nm, Kunshan Huaqiao Technology New Materials Co., Ltd.).

[0069] Example 1

[0070] This embodiment provides a method for preparing a device for tumor radiotherapy, which includes steps of preparing an absorbable polymer fiber membrane, preparing a dry hydrogel 200, and preparing a capsule 100.

[0071] 1. Preparation of absorbable polymer fiber membrane

[0072] PLGA is fully dissolved in HFIP to obtain a polymer solution, and the concentration of the mixture solution is adjusted to a range suitable for electrospinning, usually between 5% and 30% (w / v), preferably prepared as a 15wt% polymer solution. The prepared polymer solution is loaded into a 10ml syringe, and the syringe is connected to an 18G needle to prepare an absorbable polymer fiber membrane through an electrospinning process. The positive and negative electrodes of the high-voltage power supply are connected to the syringe needle and the receiving plate, respectively, with a voltage of 15kV, a distance of 20cm between the needle and the receiving plate, and a flow rate of the polymer solution of 10μl / min. The polymer solution forms a jet under the action of the electric field, which is ejected from the needle. The solvent evaporates during the jet flying to the receiving plate, and the polymer gradually solidifies into fibers. The fibers are deposited on the receiver to form a nonwoven fiber membrane. The electrospinning is placed in a fume hood (temperature 23±2℃, relative humidity 50%±1%), and the resulting fiber membrane is left in the fume hood overnight to remove the residual solvent and ensure that the organic solvent in the fiber membrane is completely volatilized.

[0073] 2. Preparation of Dry Hydrogel 200

[0074] Select an appropriate hydrogel material (such as polyethylene glycol, polyacrylic acid, polyvinyl alcohol, etc.), dissolve iohexol in an appropriate solvent (such as distilled water or physiological saline) to form a uniform solution (preferably prepared as a 10wt% iohexol solution), and then introduce the iohexol solution into the hydrogel, and adjust the pH value of the mixed solution to neutral or the required pH range to promote the formation of the hydrogel. Allow the hydrogel to solidify under certain conditions to form a stable three-dimensional network structure. Place the solidified hydrogel in a freeze dryer and perform a freeze drying process to remove moisture from the hydrogel. After freeze drying, take out the dry hydrogel 200, and finally grind it into granular dry hydrogel 200 with a ball mill, such as Figure 1 As shown, the prepared granular dry hydrogel 200 is an iodine-containing granular dry hydrogel 200.

[0075] 3. Preparation of Capsule 100

[0076] The fiber membrane prepared in step 1 is cut into a suitable size and shape, and the fiber membrane is sutured into a bag shape with absorbable sutures, such as Figure 2 and Figure 3 As shown. A proper amount of dry hydrogel 200 is loaded into the pouch 100. Preferably, the volume of the dry hydrogel 200 is 10% to 80% (preferably 60%) of the volume of the pouch 100. After the dry hydrogel 200 is loaded into the pouch 100, it is sealed with sutures to finally obtain the pouch 100 encapsulating the dry hydrogel 200. The pouch 100 prepared in this embodiment refers to an iodine-containing pouch 100.

[0077] In order to test the CT imaging performance of the pouch 100 containing the dry hydrogel 200, the present embodiment further rehydrates the pouch 100 with physiological saline (preferably the rehydration time is 30 min) and then places it into a centrifuge tube containing a PBS solution to simulate the in vivo implantation of the pouch 100. The CT imaging data on day 0 and day 7 are collected, as shown in FIG. Figure 4 As shown, the CT image can clearly display the capsule 100 with clear boundaries, that is, the capsule 100 has good CT visualization. This feature of the capsule 100 helps doctors to accurately locate the boundary between tumor tissue and normal tissue. With the position of the capsule 100 clearly identified, doctors can more accurately plan the dose distribution of radiotherapy to ensure that the radiation dose is delivered to the tumor to the maximum extent while protecting the surrounding normal tissue. Doctors can also use CT visualization to monitor the position changes of the capsule 100 and the response of the tumor to timely evaluate the treatment effect. In addition, hydrogels with good CT visualization can reduce unnecessary repeated examinations and treatments, helping to reduce overall medical costs.

[0078] This embodiment further performs a biocompatibility evaluation on the pouch 100 encapsulating the dry hydrogel 200 .

[0079] In this embodiment, cytotoxicity testing of the pouch 100 is performed in accordance with GB / T 16886.5-2017 "Biological Evaluation of Medical Devices Part 5: In vitro Cytotoxicity Test". The detection method includes: inoculating L929 cells into a 96-well plate, culturing for 24 hours to form a semi-confluent monolayer, and then contacting with the pouch 100 sample test group and control group extracts (0.2g / ml extraction ratio, 72h extraction time). After 24 hours of contact, the cell growth of the test group and the control group was observed under a microscope. The formazan formation of each control group in combination with each test sample extract concentration (0%, 25%, 50%, 75% and 100%) was measured and compared with the formazan formation of the cultured cells in the blank control group. The relative survival rate of each test sample extract concentration group was calculated, and the results are as follows. Figure 5 and 6 As shown. When the concentration of the extract is 100%, the cell viability can reach more than 70% (the cells maintain high viability), the cells are in good condition, their morphology is regular, the number of cells increases steadily within a suitable period of time, and there is no decrease in cell proliferation. This result shows that the substances released during the extraction process are non-toxic or have very low toxicity to the cells. Even at a concentration of 100% extract, the cells can still maintain a high viability, indicating that the pouch 100 has good biocompatibility.

[0080] Example 2

[0081] This embodiment provides another method for preparing a device for tumor radiotherapy, which includes steps of preparing an absorbable polymer fiber membrane, preparing a dry hydrogel 200, and preparing a capsule 100.

[0082] 1. In the preparation steps of the absorbable polymer fiber membrane, PLGA in Example 1 was replaced by PLCL, and the other steps and conditions were the same as in Example 1.

[0083] 2. In the preparation step of the dry hydrogel 200, the iohexol in Example 1 is replaced by HAp, and HAp is preferably prepared as a 10 wt% solution. The remaining steps are the same as in Example 1, but the dry hydrogel 200 is finally ground into a powdered dry hydrogel 200 by a ball mill, such as Figure 7 shown.

[0084] 3. The steps for preparing the pouch 100 are the same as those in Example 1, wherein the volume of the powdered dry hydrogel 200 is 40% of the volume of the pouch 100. The pouch 100 referred to in this example refers to a pouch 100 containing hydroxyapatite.

[0085] In this embodiment, the pouch 100 is further rehydrated with physiological saline (preferably for 30 minutes) and then placed in a centrifuge tube containing PBS solution to simulate the in vivo implantation of the pouch 100. CT imaging data on day 0 and day 7 are collected. Figure 8 As shown, the results indicate that the capsule 100 has good CT visualization properties (same as the results of Example 1).

[0086] This embodiment further performs a biocompatibility evaluation on the pouch 100 encapsulating the dry hydrogel 200. The results are as follows: Fig. 9 and 10 As shown, the results show that the cells are in good condition, their morphology is regular, the cell number increases steadily within a suitable period of time, there is no decrease in cell proliferation, and the cell viability corresponding to 100% extraction concentration is close to 70%, indicating that the pouch 100 has good biocompatibility.

[0087] Example 3

[0088] The steps and conditions for preparing the absorbable polymer fiber membrane, the dry hydrogel 200 and the pouch 100 of this embodiment are the same as those of Example 2, except that the volume of the dry hydrogel 200 is 10% of the volume of the pouch 100. The pouch 100 referred to in this embodiment refers to a pouch 100 containing hydroxyapatite.

[0089] Example 4

[0090] The preparation steps and conditions of the absorbable polymer fiber membrane, the dry hydrogel 200 and the pouch 100 of this embodiment are the same as those of embodiment 2, except that the volume of the dry hydrogel 200 is 20% of the volume of the pouch 100. The pouch 100 referred to in this embodiment refers to a pouch 100 containing hydroxyapatite.

[0091] Example 5

[0092] The preparation steps and conditions of the absorbable polymer fiber membrane, the dry hydrogel 200 and the pouch 100 of this embodiment are the same as those of embodiment 2, except that the volume of the dry hydrogel 200 is 60% of the volume of the pouch 100. The pouch 100 referred to in this embodiment refers to a pouch 100 containing hydroxyapatite.

[0093] Example 6

[0094] The preparation steps and conditions of the absorbable polymer fiber membrane, the dry hydrogel 200 and the pouch 100 of this embodiment are the same as those of embodiment 2, except that the volume of the dry hydrogel 200 is 80% of the volume of the pouch 100. The pouch 100 referred to in this embodiment refers to a pouch 100 containing hydroxyapatite.

[0095] Example 7

[0096] In this embodiment, the mechanical properties of the pouch 100 prepared in embodiments 2 to 6 were characterized to obtain the Young's modulus corresponding to the stress-strain linear range under the uniaxial compression test conditions. The results are shown in Tables 1 and Fig.12 shown.

[0097] Table 1

[0098]

[0099] Young's modulus, also known as elastic modulus, is used to characterize the elasticity or rigidity of a material. Specifically, it is used to characterize the material's ability to resist deformation. The higher the Young's modulus, the more rigid the material is and the less likely it is to deform; the lower the Young's modulus, the more flexible the material is and the easier it is to deform.

[0100] In the results in Table 1, when the volume proportion of the dry hydrogel 200 filling the pouch 100 is 10%, the Young's modulus of the pouch 100 is 21.73 kPa, and the Young's modulus under this proportion is the largest; when the volume proportion of the dry hydrogel 200 filling the pouch 100 is 20%, the Young's modulus of the pouch 100 is 4.18 kPa, and the Young's modulus under this proportion is the smallest; when the volume proportion of the dry hydrogel 200 filling the pouch 100 is 40%, the Young's modulus of the pouch 100 is 8.52 kPa; when the volume proportion of the dry hydrogel 200 filling the pouch 100 is 60%, the Young's modulus of the pouch 100 is 7.5 kPa; when the volume proportion of the dry hydrogel 200 filling the pouch 100 is 80%, the Young's modulus of the pouch 100 is 10.29 kPa.

[0101] When the dry hydrogel 200 fills a low proportion of the volume of the pouch 100, such as the first filling volume, the dry hydrogel 200 forms a good interface bond with the fiber membrane after rehydration, thereby improving the overall strength of the material. At this time, the overall Young's modulus of the pouch 100 is high, the rigidity is large, the pouch 100 is not easy to deform, and has good support characteristics. Therefore, in this embodiment, when the dry hydrogel 200 fills 10% of the volume of the pouch 100, the Young's modulus is high and can reach 21.73 kPa. Under this condition, the pouch 100 is not easy to deform.

[0102] When the volume of the pouch 100 filled with the dry hydrogel 200 gradually increases, such as from 20% to 80%, the Young's modulus generally shows a trend of gradually increasing. As the filling amount of the dry hydrogel 200 increases, the porosity of the pouch 100 material increases, resulting in a decrease in the elastic modulus of the overall material.

[0103] When the dry hydrogel 200 fills 20% of the volume of the pouch 100, the Young's modulus is the smallest, which is 4.18 kPa. Under this condition, the pouch 100 can easily conform to the tissue structure to form a fitting protective wall.

[0104] When the dry hydrogel 200 fills 80% of the volume of the pouch 100, the Young's modulus increases to 10.29 kPa. Under this condition, the filling rate of the dry hydrogel 200 in the pouch 100 is high, which can provide more material to absorb as much radiation as possible (increasing the ability to absorb radiation). At the same time, the pouch 100 has a certain rigidity and strength, is less likely to deform, and can maintain uniform stress, thereby maintaining a specific shape and position.

[0105] Example 8

[0106] In this embodiment, the thickness of the pouch 100 after rehydration is analyzed under the conditions of different volume ratios of the pouch 100 filled with the dry hydrogel 200. The appearance of the pouch 100 (after rehydration) corresponding to the different filling volumes of the dry hydrogel 200 is as follows: Fig.11As shown, the results show that: when the volume of the pouch 100 filled with dry hydrogel 200 accounts for 10%, the thickness of the pouch 100 after rehydration ranges from 2 to 2.5 mm, preferably 2.45 mm; when the volume of the pouch 100 filled with dry hydrogel 200 accounts for 20%, the thickness of the pouch 100 after rehydration ranges from 3 to 3.5 mm, preferably 3.4 mm; when the volume of the pouch 100 filled with dry hydrogel 200 accounts for 40%, the thickness of the pouch 100 after rehydration ranges from 4 to 4.5 mm, preferably 4.4 mm; when the volume of the pouch 100 filled with dry hydrogel 200 accounts for 60%, the thickness of the pouch 100 after rehydration ranges from 4.5 to 5.2 mm, preferably 5.1 mm; when the volume of the pouch 100 filled with dry hydrogel 200 accounts for 80%, the thickness of the pouch 100 after rehydration ranges from 7 to 7.5 mm, preferably 7.1 mm.

[0107] The thickness of the pouch 100 after rehydration is different under different volume ratios of the dry hydrogel 200 filling the pouch 100. Generally, thicker hydrogels can provide better physical barriers and can absorb and block more external impacts. The thickness can be selected according to the required protection level, application scenario, fit, comfort, etc.

[0108] Example 9

[0109] This embodiment provides a device for isolating tumor tissue and normal tissue in tumor radiotherapy, such as Figures 13 to 20 . The device includes a skeleton pouch 120 with a higher Young's modulus formed by filling the dry hydrogel 200 with a first filling volume in an external material, a surface pouch 130 with a lower Young's modulus in contact with human tissue and / or organs formed by filling the dry hydrogel 200 with a second filling volume in an external material, and a core pouch 110 with a greater radiation absorption rate or radiation absorption dose formed by filling the dry hydrogel 200 with a third filling volume in an external material. The first filling volume is 10%, the second filling volume is 20%, and the third filling volume is 80%. The skeleton pouch 120 filled with a 10% filling volume has a larger elastic modulus of 21.73 kPa, forming an outer contour frame to protect healthy tissue. The surface pouch 130 filled with a 20% filling volume has a smaller elastic modulus of 4.18 kPa, which is easy to conform to the tissue structure to form a fitting protective wall. Because of its low filling rate, it absorbs limited water and causes less damage to the tissue. The core pouch 110 filled with 80% fill volume has an elastic modulus of 10.29 kPa and acts as a core to absorb as much radiation as possible.

[0110] The device for isolating tumor tissue and normal tissue in tumor radiotherapy provided in this embodiment is an innovative multi-layer structural design, which makes full use of the characteristics of the dry hydrogel 200 at different filling volumes to achieve all-round protection of normal tissue and effective isolation of tumor tissue. The multi-layer structural design achieves all-round protection of normal tissue, not only provides structural support, but also designs the surface layer to ensure fit and the inner layer to maximize radiation absorption. This device optimizes the physical properties of each layer by precisely controlling the filling rate of different layers of capsules 100, so that each layer can play its best function. The device as a whole takes into account structural stability, tissue fit and radiation protection effect, greatly improving the safety and accuracy of radiotherapy. The innovative layered filling design minimizes potential damage to normal tissue while maximizing the isolation effect of tumor tissue. It has good plasticity and strong adaptability, and can be personalized according to the specific conditions of different patients.

[0111] It should be noted that the above-mentioned specific embodiments are exemplary, and those skilled in the art can come up with various solutions inspired by the disclosure of the present invention. The equivalent replacement of the raw materials selected by the present invention, the addition of auxiliary components, the selection of specific methods, etc., also belong to the disclosure scope of the present invention and fall within the protection scope of the present invention. Those skilled in the art should understand that the description of the present invention and its drawings are illustrative and do not constitute limitations on the claims. The scope of protection of the present invention is defined by the claims and their equivalents. The description of the present invention contains multiple inventive concepts, such as "preferably" and "according to a preferred embodiment", which means that the corresponding paragraph discloses an independent concept, and the applicant reserves the right to file a divisional application based on each inventive concept.

Claims

1. A device for tumor radiotherapy, the device being particularly used for isolating tumor tissue from normal tissue in tumor radiotherapy, comprising: An external material made of absorbable polymer fiber membrane and a dry hydrogel (200) filled in the external material, characterized in that: The mechanical properties of the device are controlled by the volume ratio of the dry hydrogel (200) filled in the external material.

2. The device according to claim 1, characterized in that The volume proportion of the dry hydrogel (200) filled in the external material is 5% to 100%, preferably 10% to 80%.

3. The device according to claim 1 or 2, characterized in that: The device comprises a surface pouch (130) having a lower Young's modulus and in contact with human tissue and / or organs, formed by filling the external material with a second filling volume of dry hydrogel (200), and a core pouch (110) having a greater radiation absorption rate or radiation absorption dose, formed by filling the external material with a third filling volume of dry hydrogel (200).

4. A multi-layer stacked device for tumor radiotherapy, characterized in that: Include: The dry hydrogel (200) is filled with a second filling volume into a surface bag (130) with a lower Young's modulus that contacts human tissues and / or organs and is formed by an external material, and the dry hydrogel (200) is filled with a third filling volume into a core bag (110) with a greater radiation absorption rate or radiation absorption dose formed by the external material, The core capsule (110) is used as the central layer, and the surface capsules (130) are respectively covered from the central layer to the upper and lower layers, thereby forming a multi-layer stacked device for isolating tumor tissue and normal tissue in tumor radiotherapy.

5. A multi-layer wrapped device for tumor radiotherapy, characterized in that: include: The dry hydrogel (200) is filled in a surface bag (130) with a lower Young's modulus and in contact with human tissues and / or organs formed by the external material with a second filling volume, and the dry hydrogel (200) is filled in a core bag (110) with a greater radiation absorption rate or radiation absorption dose formed by the external material with a third filling volume, The core capsule (110) is used as the central layer, and the surface capsules (130) are respectively wrapped from the central layer to the outside, thereby forming a multi-layer wrapped device for isolating tumor tissue and normal tissue in tumor radiotherapy.

6. A frame-type device for tumor radiotherapy, characterized in that: include: The dry hydrogel (200) is filled in an external material with a second filling volume to form a surface bag (130) with a lower Young's modulus in contact with human tissues and / or organs, and the dry hydrogel (200) is filled in an external material with a third filling volume to form a core bag (110) with a greater radiation absorption rate or radiation absorption dose. The surface bag (130) is covered on the outer contour frame to form a closed structure, and the core bag (110) is filled inside the closed structure, thereby forming a frame-type device for isolating tumor tissue and normal tissue in tumor radiotherapy.

7. A hemispherical device for tumor radiotherapy, characterized in that: include: The dry hydrogel (200) is filled in an external material with a second filling volume to form a surface bag (130) with a lower Young's modulus in contact with human tissues and / or organs, and the dry hydrogel (200) is filled in an external material with a third filling volume to form a core bag (110) with a greater radiation absorption rate or radiation absorption dose. The surface capsule (130) is used to form a hemispherical outer shell surface to abut against normal tissues and / or organs, and the core capsule (110) is used to form a hemispherical base surface to absorb radiation, thereby forming a hemispherical device for isolating tumor tissue and normal tissue in tumor radiotherapy.

8. A strip-shaped device for tumor radiotherapy, characterized in that: include: The dry hydrogel (200) is filled in an external material with a second filling volume to form a surface bag (130) with a lower Young's modulus in contact with human tissues and / or organs, and the dry hydrogel (200) is filled in an external material with a third filling volume to form a core bag (110) with a greater radiation absorption rate or radiation absorption dose. The core capsule (110) is taken as the center, and the surface capsule (130) is wrapped from the center outward, thereby forming a strip-shaped device for isolating tumor tissue and normal tissue in tumor radiotherapy.

9. A hydrogel composition, characterized in that: The invention comprises a bag (100) made of an absorbable polymer fiber membrane and a dry hydrogel (200) filled in the bag (100). The mechanical properties of the hydrogel composition are controlled by the volume ratio of the dry hydrogel (200) filled in the pouch (100).

10. A method for preparing a device for tumor radiotherapy, characterized in that: The following steps are involved: The absorbable polymer fiber membrane is prepared by 3D printing or electrospinning technology. Obtaining a dry hydrogel (200) by one or more methods selected from freeze drying, room temperature drying, solvent replacement, vacuum drying or supercritical drying; The dry hydrogel (200) is filled into a capsule (100) made of an absorbable polymer fiber membrane according to a specific volume ratio, thereby forming a device for tumor radiotherapy.

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