A load 32 Method for preparing ultra-thin sheet-like chitosan hydrogel patch of P

Abstract

This invention discloses a load 32 The preparation method of the ultrathin sheet-like chitosan hydrogel applicator of P includes: (1) preparing a chitosan aqueous solution; (2) adding methacrylic anhydride to the chitosan aqueous solution to obtain methacrylated chitosan; (3) preparing a methacrylated chitosan aqueous solution; (4) adding 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone to the methacrylated chitosan aqueous solution to obtain a chitosan hydrogel precursor solution; (5) coating the inner wall of a polytetrafluoroethylene mold with a superhydrophilic coating; (6) adding Na2H 32 PO4 aqueous solution and chitosan hydrogel precursor solution are added to the mold, stirred and then cured by light; (7) the cured hydrogel is taken out and sealed between two layers of transparent tape. This application can prepare an ultra-thin hydrogel applicator, thereby reducing the obstruction of radiation by the hydrogel material itself and enhancing the therapeutic effect of the applicator.

Description

Technical Field

[0001] This application relates to the field of biomedical materials technology, specifically a loading... 32 Method for preparing ultrathin sheet-like chitosan hydrogel applicators. Background Technology

[0002] Radiotherapy with isotopes is an effective clinical treatment for keloids. It works by using beta rays released by the isotope to bombard the DNA chains of cells in the irradiated area, causing cell death and disintegration, thus achieving a therapeutic effect. This method has a low recurrence rate and allows for targeted treatment of the affected area. Phosphorus-32 is a radioactive isotope of elemental phosphorus, with the symbol [symbol missing]. 32 P. 32 P is the radiation source commonly used in hospital dressings; its half-life is short, only two weeks. 32 The P-application device has the advantage of being customizable on-site according to the lesion site.

[0003] Chinese patent application CN116196541A discloses a phosphorus isotope patch, which involves placing a phosphorus isotope layer between a first base layer and a second base layer. The preparation of the phosphorus isotope layer includes multiple steps such as drawing the shape, pattern cutting, area calculation, first addition of the radionuclide, first drying, second addition of the radionuclide, and second drying. This process is cumbersome and time-consuming, wastes radionuclides, and releases radioactive aerosols into the environment.

[0004] Chinese patent application CN 116983464A discloses a loading... 32 The method for preparing the P-type hydrogel applicator overcomes the problems existing in the aforementioned phosphorus isotope layer preparation process. However, the hydrogel prepared by this method is too thick, and 32 The average range of beta rays emitted by P in tissues is 4 mm. Excessively thick hydrogels can hinder the propagation of beta rays, thus affecting the therapeutic effect. Summary of the Invention

[0005] The purpose of this application is a load 32 The present application discloses a method for preparing an ultrathin sheet-like chitosan hydrogel applicator. This application can prepare an ultrathin sheet-like chitosan hydrogel applicator.

[0006] This application provides a load 32 The preparation method of the ultrathin sheet-like chitosan hydrogel patch of P includes:

[0007] (1) Prepare a chitosan aqueous solution by adding 1-2g of chitosan to every 100mL of water;

[0008] (2) Methacrylic anhydride was added dropwise to chitosan aqueous solution to react and obtain methacrylated chitosan. The molar ratio of methacrylic anhydride to amino groups in chitosan was 5-16:1.

[0009] (3) Prepare an aqueous solution of methacrylated chitosan by adding 400mg-500mg of methacrylated chitosan to every 10mL of water;

[0010] (4) Add 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone to the aqueous solution of methacrylated chitosan to obtain a chitosan hydrogel precursor solution. The mass ratio of 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone to methacrylated chitosan is 1:8-20.

[0011] (5) Coat the inner wall of the mold made of polytetrafluoroethylene with a superhydrophilic coating and let it air dry naturally;

[0012] (6) Na2H 32 PO4 aqueous solution and chitosan hydrogel precursor solution were added to the mold, stirred and then cured by light.

[0013] (7) Remove the cured hydrogel and encapsulate it between two layers of transparent tape to obtain an ultra-thin sheet-like chitosan hydrogel applicator.

[0014] Further, step (1) specifically involves: adding chitosan powder to water, then adding acetic acid dropwise, and stirring in an oil bath at 60℃-70℃ for 30min-60min until the chitosan powder is completely dissolved; the amount of acetic acid used is: the volume of acetic acid is 1%-2% of the volume of water.

[0015] Further, step (2) specifically involves: adding methacrylic anhydride dropwise to the chitosan aqueous solution and reacting it in a water bath at 55℃-65℃ for 6-8 hours. After that, the reaction solution is adjusted to neutral, dialyzed, and then freeze-dried to obtain foamy methacrylated chitosan.

[0016] Further, step (3) specifically involves: adding methacrylated chitosan to deionized water and heating it in a water bath at 60℃-70℃ for 0.5h-1h to obtain an aqueous solution of methacrylated chitosan.

[0017] Further, in step (4), 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone is added to the aqueous solution of methacrylated chitosan and stirred at room temperature for 10 min-30 min to dissolve the 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone, thus obtaining the chitosan hydrogel precursor solution.

[0018] Furthermore, the main component of the superhydrophilic coating is polyacrylic acid.

[0019] Furthermore, in step (6), ultraviolet light with a wavelength of 365nm is used for photocuring.

[0020] Furthermore, in step (6), Na2H 32 PO4 aqueous solution is phosphorus [ 32 P] sodium acid oral solution, and Na2H 32 The volume ratio of PO4 aqueous solution to chitosan hydrogel precursor solution is 1:10-100.

[0021] Furthermore, in step (6), Na2H 32 The radioactivity of PO4 aqueous solution is 0.2 mCi / mL to 2 mCi / mL.

[0022] Compared with the prior art, this application has the following advantages and beneficial effects:

[0023] 1. Due to the surface tension of water, ordinary hydrogels are difficult to make thin. If too little hydrogel solution is added to the mold, the solution cannot cover the mold completely. However, to cover the mold completely, a large amount of hydrogel solution needs to be added, which results in an excessively thick hydrogel. In this application, the chitosan hydrogel precursor solution itself has high viscosity. Combined with a polytetrafluoroethylene mold treated with a hydrophilic coating, a very small amount of chitosan hydrogel precursor solution can be used to cover the mold completely, thereby preparing an ultra-thin hydrogel applicator. This reduces the obstruction of radiation by the hydrogel material itself and enhances the therapeutic effect of the applicator.

[0024] 2. In this application, the solid content in the chitosan hydrogel precursor solution can be as low as 4%. The significantly reduced solid content means that the molecular chains in the hydrogel also reduce their ability to block radiation, thereby further enhancing the therapeutic effect of the patch.

[0025] 3. Chitosan requires acid solubility. By using methacrylic anhydride to acylate chitosan, water-soluble methacrylated chitosan is obtained. Furthermore, the water solubility of methacrylated chitosan changes with the degree of acylation, making the preparation of chitosan hydrogel precursor solutions more convenient. Attached Figure Description

[0026] Figure 1 Here is a photograph of the actual sample from Example 1;

[0027] Figure 2 This is a schematic diagram of the thickness measurement of the sample in Example 1;

[0028] Figure 3 Here is a scanning electron microscope image of the surface of the hydrogel sample from Example 2;

[0029] Figure 4 This is a scanning electron microscope image of a cross-section of the hydrogel sample from Example 2;

[0030] Figure 5 A statistical graph showing the degree of acylation for samples with different amounts of methacrylic anhydride added;

[0031] Figure 6 Solubility statistics for samples with different degrees of acylation;

[0032] Figure 7 A statistical graph showing the retention rate of P element in samples with different nuclide concentrations;

[0033] Figure 8 This is a statistical graph showing the unit activity dose rate of samples with different thicknesses. Detailed Implementation

[0034] To make the objectives, technical solutions, and advantages of this application clearer, the technical solutions of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of this application, not all embodiments. Based on the embodiments of this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0035] It should be noted that Na2H in the following examples 32 PO4 aqueous solutions all use phosphorus from Atomic High-Tech Co., Ltd. 32 P] sodium salt oral solution.

[0036] Example 1

[0037] The load in this embodiment 32 The preparation steps of P's ultrathin sheet-like chitosan hydrogel applicator are as follows:

[0038] (1) Take 2g of chitosan powder and add it to 200mL of water, then add 2mL of acetic acid, place it in a 60℃ oil bath and stir for 60min to completely dissolve the chitosan powder and obtain a chitosan aqueous solution.

[0039] (2) Add methacrylic anhydride dropwise to the chitosan aqueous solution and react in a water bath at 60°C for 6 hours. Then, adjust the reaction solution to neutral with a 10 mol / L sodium hydroxide solution. The molar ratio of methacrylic anhydride to amino groups in chitosan is 5:1.

[0040] (3) Pour the neutral reaction solution into a dialysis bag and dialyze it in a beaker for 3 days, changing the water 5 times a day; then freeze-dry the solution for 72 hours. When the solution freezes into a foamy state, methacrylamide chitosan is prepared.

[0041] (4) Take 400 mg of methacrylated chitosan and add it to 10 mL of deionized water. Heat it in a water bath at 60 °C for 1 h to completely dissolve the methacrylated chitosan and obtain an aqueous solution of methacrylated chitosan.

[0042] (5) Add 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone to an aqueous solution of methacrylamide chitosan and stir at room temperature for 20 min to dissolve the 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone to obtain a chitosan hydrogel precursor solution; wherein the mass ratio of 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone to methacrylamide chitosan is 1:8;

[0043] (6) Take a polytetrafluoroethylene mold with a length of 50mm, a width of 50mm and a height of 3mm, apply a layer of superhydrophilic coating to the inner surface of the mold, and let it air dry for 20 minutes; in this embodiment, the superhydrophilic coating is selected from the commercially available Paiqi Nano ATF202 coating agent, whose main component is polyacrylic acid; the superhydrophilic coating can improve the hydrophilicity of the polytetrafluoroethylene mold surface and reduce its water contact angle;

[0044] (7) Na2H 32 Aqueous solutions of PO4 and methacrylamide chitosan were added to a mold and stirred until homogeneous. The mixture was then cured by UV light at a wavelength of 365 nm. Na2H... 32 The radioactivity of the PO4 aqueous solution is 0.5 mCi / mL; the Na2H added to the mold 32 The total volume of the PO4 aqueous solution and the methacrylamide chitosan aqueous solution should meet the following requirement: the total volume divided by the bottom area of ​​the mold should be 0.5 mm.

[0045] (8) Remove the cured hydrogel and encapsulate it between two layers of transparent tape to obtain the load. 32 P's ultra-thin sheet-like chitosan hydrogel applicator.

[0046] Please see Figure 1 The image shown is a photograph of the actual sample from this embodiment; please refer to [link / reference]. Figure 2 The figure shown is a schematic diagram of the thickness measurement of the sample in this embodiment. The thickness of the sample is 0.5 mm.

[0047] Example 2

[0048] The load in this embodiment 32 The preparation steps of P's ultrathin sheet-like chitosan hydrogel applicator are as follows:

[0049] (1) Take 2.5g of chitosan powder and add it to 200mL of water, then add 2mL of acetic acid, place it in a 60℃ oil bath and stir for 60min to completely dissolve the chitosan and obtain a chitosan aqueous solution.

[0050] (2) Add methacrylic anhydride dropwise to the chitosan aqueous solution and react for 6 hours. Then, adjust the reaction solution to neutral with a 10 mol / L sodium hydroxide solution. The molar ratio of methacrylic anhydride to amino groups in chitosan is 7:1.

[0051] (3) Pour the neutral reaction solution into a dialysis bag and dialyze it in a beaker for 3 days, changing the water 5 times a day; then freeze-dry the solution for 72 hours. When the solution freezes into a foamy state, methacrylamide chitosan is prepared.

[0052] (4) Take 450 mg of methacrylamide chitosan and add it to 10 mL of deionized water. Heat it in a water bath at 60 °C for 1 h to completely dissolve the methacrylamide chitosan and obtain an aqueous solution of methacrylamide chitosan.

[0053] (5) Add 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone to an aqueous solution of methacrylamide chitosan and stir at room temperature for 20 min to dissolve the 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone to obtain a chitosan hydrogel precursor solution; wherein the mass ratio of 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone to methacrylamide chitosan is 1:20;

[0054] (6) Take a polytetrafluoroethylene mold with a length of 50mm, a width of 50mm, and a height of 3mm. Apply a layer of superhydrophilic coating to the inner surface of the mold and allow it to air dry for 20 minutes. In this embodiment, the superhydrophilic coating is the commercially available Paiqi Nano ATF202 coating agent, whose main component is polyacrylic acid. The superhydrophilic coating can improve the hydrophilicity of the mold surface and reduce its water contact angle.

[0055] (7) Na2H 32 PO4 aqueous solution and methacrylamide chitosan aqueous solution were added to the mold, stirred evenly, and then cured by UV light with a wavelength of 365 nm. Na2H 32 The radioactivity of the PO4 aqueous solution is 0.5 mCi / mL; the Na2H added to the mold 32 The total volume of the PO4 aqueous solution and the methacrylated chitosan aqueous solution should meet the following requirement: the total volume divided by the bottom area of ​​the mold is 0.5 mm.

[0056] The solidified hydrogel sample was removed and its microstructure was observed using a benchtop scanning electron microscope (SEM). The hydrogel sample was first freeze-dried, its cross-section was polished, and then it underwent drying and gold sputtering treatments before observation. The resulting SEM images are shown below. Figure 3-4 .in, Figure 3 The surface of the hydrogel sample, Figure 4 This is a cross-section of a hydrogel sample. From Figure 3-4It can be seen that the cross-linked network structure of the hydrogel ensures that the hydrogel has good mechanical properties, and the uniformly distributed dense pores can ensure... 32 P is uniformly loaded.

[0057] Example 3

[0058] In this embodiment, three groups of samples were prepared. The only difference between each group of samples was the molar ratio of methacrylic anhydride to amino groups in chitosan. The preparation steps are as follows:

[0059] (1) Take 3g of chitosan powder and add it to 200mL of water, then add 2mL of acetic acid, place it in a 60℃ oil bath and stir for 60min to completely dissolve the chitosan and obtain a chitosan aqueous solution.

[0060] (2) Add methacrylic anhydride dropwise to the chitosan aqueous solution and react in a water bath at 55-65℃ for 6 hours. Then, adjust the reaction solution to neutral with a 10mol / L sodium hydroxide solution. The molar ratios of methacrylic anhydride to amino groups in chitosan in the three groups of samples were 5:1, 10:1, and 15:1, respectively.

[0061] (3) Pour the neutral reaction solution into a dialysis bag and dialyze it in a beaker for 3 days, changing the water 5 times a day; then freeze-dry the solution for 72 hours. When the solution freezes into a foamy state, methacrylamide chitosan is prepared.

[0062] (4) Take 500 mg of methacrylated chitosan and add it to 10 mL of deionized water. Heat it in a 60 °C water bath for 1 h to completely dissolve the methacrylated chitosan and obtain an aqueous solution of methacrylated chitosan.

[0063] (5) Add 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone to an aqueous solution of methacrylamide chitosan and stir at room temperature for 20 min to dissolve the 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone to obtain a chitosan hydrogel precursor solution; wherein the mass ratio of 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone to methacrylamide chitosan is 1:15;

[0064] (6) Take a polytetrafluoroethylene mold with a length of 50mm, a width of 50mm and a height of 3mm, apply a layer of superhydrophilic coating to the inner surface of the mold, and let it air dry for 20 minutes; in this embodiment, the superhydrophilic coating is selected from the commercially available Paiqi Nano ATF202 coating agent, whose main component is polyacrylic acid; the superhydrophilic coating can improve the hydrophilicity of the polytetrafluoroethylene mold surface and reduce its water contact angle;

[0065] (7) Na2H 32PO4 aqueous solution and methacrylamide chitosan aqueous solution were added to the mold, stirred evenly, and then cured by UV light with a wavelength of 365 nm. Na2H 32 The radioactivity of the PO4 aqueous solution is 1 mCi / mL; the Na2H added to the mold 32 The total volume of the PO4 aqueous solution and the methacrylated chitosan aqueous solution should meet the following requirement: the total volume divided by the bottom area of ​​the mold is 0.5 mm.

[0066] (8) Remove the solidified hydrogel sample.

[0067] Five mg of each of the three groups of samples were taken to test the degree of acylation. The samples taken here were methacrylated chitosan prepared in step (3). The detection method was as follows: the sample was dissolved in 0.6 mL of D2O, added to the NMR tube using a syringe, and NMR spectroscopy was performed using a nuclear magnetic resonance spectrometer. The degree of substitution of methacrylic anhydride, i.e., the degree of acylation, was calculated from the NMR spectroscopy results. The results are shown in […]. Figure 5 As shown, the horizontal axis represents the molar ratio of methacrylic anhydride to the amino groups in chitosan. Figure 5 It can be seen that the degree of acylation increases with the increase of the amount of methacrylic anhydride added.

[0068] 100 mg of each of the three groups of samples were taken, and the water solubility was determined by turbidimetry: the sample was dissolved in 5 ml of deionized water, and the deionized water was slowly added to the solution. The transmittance of the solution at 500 nm was measured using a UV-Vis spectrometer. The results are as follows. Figure 6 As shown, the horizontal axis represents the molar ratio of methacrylic anhydride to the amino groups in chitosan. Figure 6 It can be seen that as the degree of acylation increases, the solubility concentration of methacrylated chitosan in aqueous solution also increases. This may be because after chitosan acylation, the methacrylic anhydride grafted onto it reduces the intermolecular forces of chitosan's CS, thereby improving its water solubility.

[0069] Example 4

[0070] In this embodiment, four groups of samples were prepared. The only difference between each group of samples was the radioactivity of the nuclide. The preparation steps are as follows:

[0071] (1) Take 3g of chitosan powder and add it to 200mL of water, then add 2mL of acetic acid, place it in a 60℃ oil bath and stir for 60min to completely dissolve the chitosan and obtain a chitosan aqueous solution.

[0072] (2) Add methacrylic anhydride dropwise to the chitosan aqueous solution and react in a water bath at 55-65℃ for 6 hours. Then, adjust the reaction solution to neutral with a 10mol / L sodium hydroxide solution. The molar ratio of methacrylic anhydride to amino groups in chitosan is 5:1.

[0073] (3) Pour the neutral reaction solution into a dialysis bag and dialyze it in a beaker for 3 days, changing the water 5 times a day; then freeze-dry the solution for 72 hours. When the solution freezes into a foamy state, methacrylamide chitosan is prepared.

[0074] (4) Take 500 mg of methacrylated chitosan and add it to 10 mL of deionized water. Heat it in a 60 °C water bath for 1 h to completely dissolve the methacrylated chitosan and obtain an aqueous solution of methacrylated chitosan.

[0075] (5) Add 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone to an aqueous solution of methacrylamide chitosan and stir at room temperature for 20 min to dissolve the 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone to obtain a chitosan hydrogel precursor solution; wherein the mass ratio of 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone to methacrylamide chitosan is 1:15;

[0076] (6) Take a polytetrafluoroethylene mold with a length of 50mm, a width of 50mm and a height of 3mm, apply a layer of superhydrophilic coating to the inner surface of the mold, and let it air dry for 20 minutes; in this embodiment, the superhydrophilic coating is selected from the commercially available Paiqi Nano ATF202 coating agent, whose main component is polyacrylic acid; the superhydrophilic coating can improve the hydrophilicity of the polytetrafluoroethylene mold surface and reduce its water contact angle;

[0077] (7) Na2H 32 Aqueous solutions of PO4 and methacrylamide chitosan were added to a mold, stirred until homogeneous, and then cured by UV light at a wavelength of 365 nm. The Na2H added to the mold... 32 The total volume of the PO4 aqueous solution and the methacryloylchitosan aqueous solution should meet the following requirement: the total volume divided by the bottom area of ​​the mold should be 0.5 mm². The radioactivity of the nuclides in the four groups of samples were 0.5 mCi / mL, 1 mCi / mL, and 2 mCi / mL, respectively.

[0078] Quantitative analysis of the four groups of samples in this example was performed using ICP (Inductively Coupled Plasma Spectrometry), and statistical analysis was conducted. 32 Statistical values ​​of P content, results are shown in... Figure 7 The x-axis represents the radioactivity of the nuclide. From Figure 7 It can be seen that the loss of P element in each group of samples after gelation is within 20%, which proves that the radionuclide utilization rate is high during the preparation of the applicator.

[0079] Example 5

[0080] In this embodiment, three groups of samples were prepared, with the only difference between each group being their thickness. The preparation steps are as follows:

[0081] (1) Take 4g of chitosan powder and add it to 200mL of water, then add 2mL of acetic acid, place it in a 60℃ oil bath and stir for 60min to completely dissolve the chitosan and obtain a chitosan aqueous solution.

[0082] (2) Add methacrylic anhydride dropwise to the chitosan aqueous solution and react in a water bath at 55-65℃ for 6 hours. Then, adjust the reaction solution to neutral with a 10mol / L sodium hydroxide solution. The molar ratio of methacrylic anhydride to amino groups in chitosan is 16:1.

[0083] (3) Pour the neutral reaction solution into a dialysis bag and dialyze it in a beaker for 3 days, changing the water 5 times a day; then freeze-dry the solution for 72 hours. When the solution freezes into a foamy state, methacrylamide chitosan is prepared.

[0084] (4) Take 500 mg of methacrylated chitosan and add it to 10 mL of deionized water. Heat it in a 60 °C water bath for 1 h to completely dissolve the methacrylated chitosan and obtain an aqueous solution of methacrylated chitosan.

[0085] (5) Add 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone to an aqueous solution of methacrylamide chitosan and stir at room temperature for 20 min to dissolve the 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone to obtain a chitosan hydrogel precursor solution; wherein the mass ratio of 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone to methacrylamide chitosan is 1:16;

[0086] (6) Take a polytetrafluoroethylene mold with a length of 50mm, a width of 50mm and a height of 3mm, apply a layer of superhydrophilic coating to the inner surface of the mold, and let it air dry for 20 minutes; in this embodiment, the superhydrophilic coating is selected from the commercially available Paiqi Nano ATF202 coating agent, whose main component is polyacrylic acid; the superhydrophilic coating can improve the hydrophilicity of the polytetrafluoroethylene mold surface and reduce its water contact angle;

[0087] (7) Na2H 32 PO4 aqueous solution and methacrylamide chitosan aqueous solution were added to the mold, stirred evenly, and then cured by UV light with a wavelength of 365 nm. Na2H 32 The radioactivity of the PO4 aqueous solution was 0.35 mCi / mL; for the three groups of samples, the Na2H added to the mold... 32 The total volumes of the PO4 aqueous solution and the methacrylamide chitosan aqueous solution satisfy the following conditions: the total volume divided by the bottom area of ​​the mold is 0.4 mm, 0.5 mm, and 1 mm, respectively. That is, the thicknesses of the three groups of samples are 0.4 mm, 0.5 mm, and 1 mm, respectively.

[0088] Hydrogel samples were extracted, and the unit activity dose rate of samples with different thicknesses was statistically analyzed. The results are shown in [Figure number missing]. Figure 8 ,from Figure 8 It can be seen that, with a labeled activity of 0.35 mCi, the unit activity dose rate of the 1 mm thick sample decreased from 1101 mGy / (h*mCi) to 1068 mGy / (h*mCi) compared to the 0.4 mm thick sample. This indicates that the hydrogel thickness has a significant impact on activity, and making the hydrogel in the applicator thinner can better utilize the nuclide.

[0089] Note that the above are merely preferred embodiments and the technical principles employed in this application. Those skilled in the art will understand that this application is not limited to the specific embodiments described herein, and various obvious changes, readjustments, and substitutions can be made without departing from the scope of protection of this application. Therefore, although this application has been described in detail through the above embodiments, this application is not limited to the above embodiments. Many other equivalent embodiments may be included without departing from the concept of this application, all of which fall within the scope of protection of this application.

Claims

1. A load 32 A method for preparing an ultrathin sheet-like chitosan hydrogel patch of P, characterized in that it includes: (1) Prepare a chitosan aqueous solution by adding 1-2g of chitosan to every 100mL of water; (2) Methacrylic anhydride was added dropwise to chitosan aqueous solution to react and obtain methacrylated chitosan. The molar ratio of methacrylic anhydride to amino groups in chitosan was 5-16:

1. (3) Prepare an aqueous solution of methacrylated chitosan by adding 400mg-500mg of methacrylated chitosan to every 10mL of water; (4) Add 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone to the aqueous solution of methacrylated chitosan to obtain a chitosan hydrogel precursor solution. The mass ratio of 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone to methacrylated chitosan is 1:8-20. (5) Coat the inner wall of the mold made of polytetrafluoroethylene with a superhydrophilic coating and let it air dry naturally; (6) Na2H 32 PO4 aqueous solution and chitosan hydrogel precursor solution were added to the mold, stirred and then cured by light. (7) Remove the cured hydrogel and encapsulate it between two layers of transparent tape to obtain an ultra-thin sheet-like chitosan hydrogel applicator; The main component of the superhydrophilic coating is polyacrylic acid.

2. The method for preparing the ultrathin sheet-like chitosan hydrogel patch as described in claim 1, characterized in that: Step (1) is as follows: Take chitosan powder and add it to water, then add acetic acid dropwise, place it in an oil bath at 60℃-70℃ and stir for 30min-60min until the chitosan powder is completely dissolved; the amount of acetic acid used is: the volume of acetic acid is 1%-2% of the volume of water.

3. The method for preparing the ultrathin sheet-like chitosan hydrogel patch as described in claim 1, characterized in that: Step (2) is as follows: add methacrylic anhydride dropwise to the chitosan aqueous solution and react in a water bath at 55℃-65℃ for 6h-8h. Then adjust the reaction solution to neutral, dialyze the neutral reaction solution, and freeze dry to obtain foamy methacrylated chitosan.

4. The method for preparing the ultrathin sheet-like chitosan hydrogel patch as described in claim 1, characterized in that: Step (3) is as follows: Take methacrylated chitosan and add it to deionized water, and heat it in a water bath at 60℃-70℃ for 0.5h-1h to obtain an aqueous solution of methacrylated chitosan.

5. The method for preparing the ultrathin sheet-like chitosan hydrogel patch as described in claim 1, characterized in that: In step (4), 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone is added to the aqueous solution of methacrylated chitosan and stirred at room temperature for 10 min-30 min to dissolve the 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylphenylacetone, thus obtaining the chitosan hydrogel precursor solution.

6. The method for preparing the ultrathin sheet-like chitosan hydrogel patch as described in claim 1, characterized in that: In step (6), ultraviolet light with a wavelength of 365nm is used for photocuring.

7. The method for preparing the ultrathin sheet-like chitosan hydrogel patch as described in claim 1, characterized in that: In step (6), Na2H 32 PO4 aqueous solution is phosphorus [ 32 P] sodium acid oral solution, and Na2H 32 The volume ratio of PO4 aqueous solution to chitosan hydrogel precursor solution is 1:10-100.

8. The method for preparing the ultrathin sheet-like chitosan hydrogel patch as described in claim 1, characterized in that: In step (6), Na2H 32 The radioactivity of PO4 aqueous solution is 0.2 mCi / mL to 2 mCi / mL.

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