Radiotherapy positioning membrane material and preparation method and application thereof

Abstract

The invention relates to the field of medical materials, in particular to a material for preparing a radiotherapy positioning film and a preparation method of the material. The material is formed by melting, blending and crosslinking polycaprolactone and diisocyanate, the molecular weight of the polycaprolactone is 40000-80000 g / mol, the end groups of the polycaprolactone comprise hydroxyl and carboxyl, and the content of the end groups is 0.025-0.05 mmol / g; the mass ratio of the polycaprolactone to the diisocyanate is 100: (0.5 to 12); the preparation method of the material comprises the following steps: (1) carrying out melt blending on dried polycaprolactone and diisocyanate, and reacting to obtain blend granules; and (2) carrying out hot press molding on the blend granules obtained in the step (1), cooling, and opening the mold to obtain the blended cross-linked polycaprolactone capable of being used as the radiotherapy positioning film material. The radiotherapy positioning film has excellent mechanical properties and shape memory function, the tensile strength of the radiotherapy positioning film reaches up to 44.4 MPa, the elongation at break reaches up to 1532.2%, the Young modulus can reach up to 162.2 MPa, the shape recovery rate and the shape fixation rate can be kept 100%, and the radiotherapy positioning film can be repeatedly used and has good application prospects.

Description

Technical Field

[0001] The present invention relates to the field of medical materials, in particular to a material for preparing a radiotherapy positioning membrane, and also to a preparation method and application of the material. Background Art

[0002] Radiotherapy is an important means of tumor treatment, which requires the use of high-energy rays to irradiate the lesion site multiple times (for example, 5 times a week for several weeks). In order to better implement the radiotherapy plan and make the radiotherapy operation repeatable, it is usually necessary to use auxiliary measures such as vacuum cushions and positioning films to fix the patient's position. Among them, vacuum cushions are highly comfortable and have good positioning repeatability, but there is a risk of air leakage and they take up a large storage space. Positioning films usually use polymer materials with certain thermoplastic properties. After covering the patient's position, they are stretched and fixed to meet special personalized needs. However, the melting temperature of such materials is usually low (around 50°C), and they are easy to deform during storage and storage.

[0003] Polycaprolactone (PCL) is an aliphatic, semicrystalline polymer with excellent biodegradability, environmental friendliness, nontoxicity, skin-contact resistance, and good flexibility and processability. However, its poor mechanical properties, thermal stability, and solvent resistance limit its application in radiotherapy targeting. PCL has a low melting point (60°C), making it amenable to crosslinking modification. Currently, there are two main methods for crosslinking PCL: the first involves melt blending PCL with peroxides and then hot pressing to produce crosslinked PCL. However, to ensure crosslinking, hot pressing requires high temperatures, resulting in irregular and uneven crosslinking, which compromises tensile properties and results in relatively low tensile strength and elongation at break. The second method involves melt blending PCL with an irradiation crosslinking agent and then hot pressing to produce a blend film. Finally, crosslinking is performed under Co-60 or electron beam irradiation to produce the crosslinked PCL. This method requires Co-60 or electron beam irradiation, increasing production steps and economic costs.

[0004] The present invention adopts a reactive blending method to prepare cross-linked polycaprolactone, selects high molecular weight polycaprolactone, and adjusts the cross-linking degree of the material by changing the amount of diisocyanate to generate a uniform and regular cross-linked structure, giving the material excellent mechanical properties and shape memory properties. Summary of the Invention

[0005] The purpose of the present invention is to provide a radiotherapy positioning membrane material based on polycaprolactone, and also provide a corresponding preparation method and application.

[0006] Based on the above purpose, the present invention adopts the following technical solutions:

[0007] In the first aspect, the present invention provides a radiotherapy positioning membrane material, which is formed by melt blending and cross-linking of polycaprolactone and diisocyanate, the molecular weight of the polycaprolactone is 40,000 to 80,000 g / mol, the end groups of the polycaprolactone include hydroxyl and carboxyl groups, and the end group content is 0.025 to 0.05 mmol / g; the mass ratio of the polycaprolactone to the diisocyanate is 100:(0.5 to 12).

[0008] The mass ratio of polycaprolactone to diisocyanate is preferably 100:(0.5 to 7).

[0009] More preferably, the polycaprolactone end group content is 0.025-0.04 mmol / g; and the mass ratio of polycaprolactone to diisocyanate is 100:(1-3).

[0010] Preferably, the molecular weight of the polycaprolactone is 50,000 g / mol.

[0011] Preferably, the diisocyanate is selected from one or more of toluene diisocyanate, diphenylmethane diisocyanate, hexamethylene diisocyanate, isophorone diisocyanate, and dicyclohexylmethane diisocyanate.

[0012] More preferably, the diisocyanate is diphenylmethane diisocyanate.

[0013] Preferably, the reactive blended cross-linked polycaprolactone has a tensile strength of 33.4 to 42.8 MPa and an elongation at break of 1149% to 1568.4%.

[0014] In a second aspect, the present invention provides a method for preparing the radiotherapy positioning membrane material according to the first aspect, which specifically comprises the following steps:

[0015] (1) melt-blending the dried polycaprolactone and diisocyanate to obtain blend pellets after reaction;

[0016] (2) hot-pressing the blend pellets obtained in step (1), cooling, and opening the mold to obtain a blended cross-linked polycaprolactone that can be used as a radiotherapy positioning membrane material.

[0017] Preferably, in step (2), the temperature of the hot pressing molding is 70-90°C, the pressure is 5-10 MPa, the holding time is 1-10 min, and the mold is opened after cooling to 25-35°C.

[0018] More preferably, the temperature of the hot pressing molding is 80° C., the pressure is 10 MPa, and the holding time is 10 min.

[0019] Preferably, in step (1), the polycaprolactone is dried at a temperature of 40 to 50° C. and for a time of 8 to 24 hours.

[0020] More preferably, in step (1), the polycaprolactone is dried at a temperature of 40° C. and for a time of 12 h.

[0021] Preferably, the melt blending temperature is 70-90° C., and the melt blending time is 6-10 minutes.

[0022] More preferably, the melt blending temperature is 80° C., and the melt blending time is 10 min.

[0023] In a third aspect, the present invention provides an application of the radiotherapy positioning membrane material, wherein the radiotherapy positioning membrane material is hot-pressed into a radiotherapy positioning membrane with a thickness of 1.6 to 3.0 mm, softened at 70 to 90°C for 3 to 5 minutes before use, and then the softened membrane is shaped and cooled at the position where it needs to be fixed.

[0024] Compared with the prior art, the present invention has the following positive and beneficial effects:

[0025] (1) The present invention utilizes a reactive blending method to prepare a cross-linked polycaprolactone for use in preparing radiotherapy positioning membranes. High molecular weight polycaprolactone is selected. By varying the mass ratio of polycaprolactone to diisocyanate, not only can the degree of cross-linking of the material be regulated, but a uniform and regular cross-linked structure can also be generated, imparting excellent mechanical and shape memory properties to the material. During the reactive blending process, the terminal hydroxyl or carboxyl groups of the polycaprolactone first undergo a chain extension reaction with the terminal NCO group of the diisocyanate, and then react with excess NCO to form a cross-linked structure.

[0026]

[0027] Therefore, when the content of diisocyanate is low (0.5wt%), polycaprolactone and diisocyanate mainly undergo chain extension reaction, the crosslinking degree is very low, the gel content is small, and the effect on the crystallization temperature and crystallinity of polycaprolactone is very small. To a certain extent, the tensile strength and elongation at break are improved. However, due to its low gel content, its shape recovery rate is low (65%), which cannot meet the shape recovery performance requirements of radiotherapy positioning membranes. As the content of diisocyanate increases to 3wt%, polycaprolactone and diisocyanate first undergo chain extension reaction, and then react with excess NCO to form a regular cross-linked structure. The gel content is moderate, which makes the shape recovery of polycaprolactone The crystallization temperature and degree of crystallization decreased slightly, but still met the requirements of radiotherapy positioning film cooling and shaping. In addition, its tensile strength and elongation at break continued to increase, and its shape recovery rate increased to 100%, meeting the requirements of radiotherapy positioning film for shape recovery performance; when the content of diisocyanate increased to 7wt%, the gel content of polycaprolactone was high, resulting in a decrease in its tensile strength and elongation at break. Although its shape memory recovery rate met the requirements of radiotherapy positioning film for shape recovery performance, the higher gel content caused the crystallization temperature and degree of crystallization to further decrease, and shaping and curing needed to be completed at a lower temperature, which could not meet the requirements of radiotherapy positioning film cooling and shaping.

[0028] (2) The cross-linked polycaprolactone provided by the present invention has a regular structure, fewer production processes, and saves costs. Its tensile strength is as high as 44.4 MPa, its elongation at break is as high as 1532.2%, its Young's modulus can reach 162.2 MPa, and its shape recovery rate and shape fixation rate can both be maintained at 100%. Therefore, the radiotherapy positioning film of the present invention has excellent mechanical properties and shape memory function, and can be reused many times, which is more economical and environmentally friendly and has good application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 The photographs are of the dissolved states of the samples of Examples 1 to 6 and Comparative Example 1 in dichloromethane;

[0030] Figure 2 : are the tensile curves of the samples of Examples 1 to 6 and Comparative Example 1;

[0031] Figure 3 These are photos of the deformation process of the samples prepared in Examples 1 to 6. DETAILED DESCRIPTION

[0032] The present invention is further described below with reference to specific examples, which however do not limit the scope of the present invention.

[0033] Example 1:

[0034] (1) Polycaprolactone (molecular weight of 50,000 g / mol, end groups including hydroxyl and carboxyl groups, and end group content of 0.04 mmol / g) was dried in a vacuum oven at 40°C for 12 h; the dried polycaprolactone and diphenylmethane diisocyanate were melt-blended in an internal mixer at a mass ratio of 100:0.5 at a melt-blending temperature of 80°C, a rotation speed of 60 r / min, and a blending time of 10 min to obtain reactive blend pellets;

[0035] (2) The blend pellets were cut into pieces and hot-pressed by a vacuum laminator. The hot-pressing temperature was 80°C, the pressure was 10 MPa, and the holding time was 10 min. After hot-pressing, the temperature was lowered to 35°C and the mold was opened to obtain reactive blended cross-linked polycaprolactone.

[0036] Example 2:

[0037] The content of Example 2 is basically the same as that of Example 1, except that in step (1), the mass ratio of polycaprolactone to diphenylmethane diisocyanate is 100:1.

[0038] Example 3:

[0039] The content of Example 3 is basically the same as that of Example 1, except that in step (1), the mass ratio of polycaprolactone to diphenylmethane diisocyanate is 100:2.

[0040] Example 4:

[0041] The content of Example 4 is substantially the same as that of Example 1, except that in step (1), the mass ratio of polycaprolactone to diphenylmethane diisocyanate is 100:3.

[0042] Example 5:

[0043] The content of Example 5 is substantially the same as that of Example 1, except that in step (1), the mass ratio of polycaprolactone to diphenylmethane diisocyanate is 100:5.

[0044] Example 6:

[0045] The content of Example 6 is basically the same as that of Example 1, except that in step (1), the mass ratio of polycaprolactone to diphenylmethane diisocyanate is 100:7.

[0046] Example 7:

[0047] The content of Example 7 is basically the same as that of Example 4, except that: in step (1), the molecular weight of polycaprolactone is 40,000 g / mol, the end groups of polycaprolactone include hydroxyl groups and carboxyl groups, and the end group content is 0.05 mmol / g; the drying temperature of polycaprolactone is 50°C, and the drying time is 8 h; the temperature of the melt blending is 70°C, and the melt blending time is 6 min; in step (2), the temperature of the hot pressing molding is 70°C, the pressure is 5 MPa, the holding time is 1 min, and the temperature of the mold opening after cooling is 25°C.

[0048] Example 8:

[0049] The content of Example 8 is basically the same as that of Example 4, except that: in step (1), the molecular weight of the polycaprolactone is 80,000 g / mol, the end groups of the polycaprolactone include hydroxyl groups and carboxyl groups, and the end group content is 0.025 mmol / g; the drying temperature of the polycaprolactone is 45°C, and the drying time is 24 h; the temperature of the melt blending is 90°C, and the melt blending time is 8 min; in step (2), the temperature of the hot pressing molding is 90°C, the pressure is 8 MPa, the holding time is 5 min, and the temperature of the mold opening after cooling is 30°C.

[0050] Comparative Example 1:

[0051] The contents of Comparative Example 1 are substantially the same as those of Example 1, except that in step (1), the blend pellets contain only polycaprolactone.

[0052] Sample characterization and performance testing:

[0053] (1) Analysis of gel content of reactive blended cross-linked polycaprolactone

[0054] The cross-linked polycaprolactone prepared in Examples 1 to 6 and Comparative Example 1 was dissolved in dichloromethane to determine the gel content, as shown in Tables 1 and Figure 1 As shown in Table 1 and Figure 1 As can be seen, since no diphenylmethane diisocyanate was added in Comparative Example 1, the linear polycaprolactone was obtained without chain extension or crosslinking. The polycaprolactone completely dissolved in dichloromethane, and its gel content was 0%. In Example 1, only 0.5 parts of diphenylmethane diisocyanate was added, and the polycaprolactone and diphenylmethane diisocyanate in the system primarily underwent a chain extension reaction, resulting in a very low degree of crosslinking and a gel content of only 5.0%. Therefore, the vast majority of the material dissolved in the dichloromethane, with only a very small amount of white material remaining in the solution. In Examples 2 to 6, as the diphenylmethane diisocyanate content increased, the polycaprolactone in the system underwent a crosslinking reaction with diphenylmethane diisocyanate, only swelling without dissolving in dichloromethane, and the gel content gradually increased, i.e., the degree of crosslinking increased, indicating that crosslinked polycaprolactones with varying degrees of crosslinking were successfully prepared through reactive blending.

[0055] Table 1 Gel content in cross-linked polycaprolactone prepared in Examples 1 to 6 and Comparative Example 1

[0056]

[0057] (2) Reactive blended cross-linked polycaprolactone film tensile test and shape memory test

[0058] The reactive blended cross-linked polycaprolactone films prepared in Examples 1 to 6 and Comparative Example 1 were subjected to tensile tests. The test results are shown in Table 2. Figure 2 As shown in Table 2, as the content of diphenylmethane diisocyanate increases, the crystallization temperature and crystallinity of the cross-linked polycaprolactone in Examples 1 to 6 gradually decrease. This is because cross-linking inhibits the movement and crystallization of the molecular chain. The higher the degree of cross-linking, the greater the inhibition of crystallization, and the lower the crystallization temperature and crystallinity. Figure 2 It can be seen that the tensile strength, elongation at break, and Young's modulus of Examples 1 to 6 are all higher than those of Comparative Example 1. However, with the increase of the diphenylmethane diisocyanate content, the tensile strength, elongation at break, and Young's modulus of Examples 1 to 6 first increase and then decrease, with Example 4 showing the best tensile strength and Young's modulus. This is because appropriate crosslinking improves the tensile properties of the material, while excessive crosslinking adversely affects the tensile properties of the cross-linked polycaprolactone.

[0059] Table 2 Effects of different addition amounts of diphenylmethane diisocyanate on the structure and properties of cross-linked polycaprolactone

[0060]

[0061] The shape memory test results of the reactive blended cross-linked polycaprolactone films prepared in Examples 1 to 6 and Comparative Example 1 are as follows: Figure 3 As shown in Table 2 and Figure 3 It can be seen that the linear polycaprolactone in Comparative Example 1 does not have shape memory properties because it does not have a cross-linked structure. The cross-linked polycaprolactones in Examples 1 to 6 all have shape memory properties, among which Examples 3 to 4 have appropriate gel content, crystallization temperature and crystallinity, high tensile strength and elongation at break, and excellent shape memory fixation rate (100%) and recovery rate (100%). Therefore, the reactive blending method can be used to prepare cross-linked polycaprolactone, and this material has excellent mechanical properties and shape memory properties. This method is simple to operate and easy to implement, making the cross-linked system structure regular, uniform and adjustable, with fewer production processes and cost savings. It can be used as a radiotherapy positioning membrane and can be reused multiple times, which is more economical and environmentally friendly and has good application prospects.

[0062] The above embodiments are specific implementation methods of the present invention, but the implementation methods of the present invention are not limited to the above embodiments. Any other combination, change, modification, substitution, and simplification that does not exceed the design concept of the present invention shall fall within the scope of protection of the present invention.

Claims

1. A radiotherapy positioning membrane material, characterized in that: The material is formed by melt-blending and cross-linking polycaprolactone and diisocyanate, the molecular weight of the polycaprolactone is 40,000 to 80,000 g / mol, the end groups of the polycaprolactone include hydroxyl groups and carboxyl groups, and the end group content is 0.025 to 0.05 mmol / g; the mass ratio of the polycaprolactone to the diisocyanate is 100:(0.5 to 12).

2. The radiotherapy positioning membrane material according to claim 1, characterized in that: The mass ratio of the polycaprolactone to diisocyanate is preferably 100:(0.5-7).

3. The radiotherapy positioning membrane material according to claim 1, characterized in that: The diisocyanate is selected from one or more of toluene diisocyanate, diphenylmethane diisocyanate, hexamethylene diisocyanate, isophorone diisocyanate, and dicyclohexylmethane diisocyanate.

4. The radiotherapy positioning membrane material according to claim 1, characterized in that: The tensile strength of the radiotherapy positioning membrane material is 33.4-42.8 MPa; the elongation at break is 1149%-1568.4%.

5. The method for preparing the radiotherapy positioning membrane material according to any one of claims 1 to 4, characterized in that: The specific steps include: (1) Melting and blending the dried polycaprolactone and diisocyanate to obtain blend pellets after reaction; (2) The blended pellets obtained in step (1) are hot-pressed into a mold, cooled, and opened to obtain a blended cross-linked polycaprolactone that can be used as a radiotherapy positioning membrane material.

6. The method for preparing the radiotherapy positioning membrane material according to claim 4, characterized in that: In step (2), the temperature of the hot pressing molding is 70-90°C, the pressure is 5-10 MPa, the holding time is 1-10 min, and the mold is opened after cooling to 25-35°C.

7. The method for preparing the radiotherapy positioning membrane material according to claim 4, characterized in that: In step (1), the polycaprolactone is dried at a temperature of 40 to 50°C and for a time of 8 to 24 hours.

8. The method for preparing the radiotherapy positioning membrane material according to claim 4, characterized in that: In step (1), the melt blending temperature is 70 to 90° C., and the melt blending time is 6 to 10 minutes.

9. Use of the radiotherapy positioning membrane material according to any one of claims 1 to 4, characterized in that: The following steps are involved: The radiotherapy positioning film material is hot-pressed into a radiotherapy positioning film with a thickness of 1.6 to 3.0 mm. Before use, it is softened at 70 to 90° C. for 3 to 5 minutes, and then the softened film is shaped at a position where it needs to be fixed and cooled.

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