Polyamino acid material sensitized by microwave hyperthermia as well as preparation method and application of polyamino acid material
By preparing polyamino acid materials as microwave sensitizers, the problems of uneven heating and poor biocompatibility in microwave body shaping have been solved, achieving efficient and safe fat cell heating and lipolysis, reducing the number of treatments and improving clinical outcomes.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- CHANGCHUN INSTITUTE OF APPLIED CHEMISTRY CHINESE ACADEMY OF SCIENCES
- Filing Date
- 2026-01-22
- Publication Date
- 2026-04-21
AI Technical Summary
Existing microwave body shaping techniques result in uneven heating of adipose tissue, leading to low energy efficiency and requiring multiple treatments. Furthermore, existing microwave sensitizing materials have poor biocompatibility and pose a risk of inflammatory reactions.
Polyamino acid materials are used as microwave sensitizers. Polyamino acids, polyamino acid salts, or polyethylene glycol-modified polyamino acids are prepared through ring-opening polymerization. These materials are used to efficiently absorb microwave energy and convert it into heat energy, thereby increasing the local temperature rise and enhancing the heating specificity and efficiency of adipocytes.
It significantly increases the microwave heat generation temperature by 5-8℃, improves fat dissolving efficiency, reduces the number of treatments, enhances fat decomposition effect, and ensures biosafety, solving the problems of low energy utilization efficiency and insufficient heating of target tissue in existing technologies.
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Abstract
Description
Technical Field
[0001] This invention belongs to the field of biomaterials technology, specifically relating to a microwave thermotherapy-sensitizing polyamino acid material, its preparation method, and its application. Background Technology
[0002] Microwave body sculpting, as an important non-invasive fat management technique, aims to selectively heat adipose tissue using microwave energy, inducing apoptosis or destruction of fat cells through thermal effects, which are then eliminated through the body's metabolic pathways. However, traditional microwave energy is difficult to precisely control within the heterogeneous composition and density of adipose tissue, resulting in low energy deposition efficiency in the target area. Specifically, heating is often uneven, with some fat cells underheated while adjacent non-target tissues, such as the skin, may suffer unnecessary thermal risks, usually requiring external cooling systems for epidermal protection. This low energy efficiency directly leads to limited effects from a single treatment, often requiring multiple treatments to achieve the desired shaping effect, significantly prolonging the treatment cycle and increasing the burden on patients. More critically, current microwave fat reduction techniques cannot ensure that all target fat cells suffer lethal thermal damage sufficient to completely ablate them. Due to uneven energy distribution, especially at the edges of the treatment area where the temperature gradient decreases significantly and heat is insufficient, fat cells in this area may only suffer sublethal thermal damage. These fat cells in a reversibly damaged state have a strong self-repair ability. After treatment, they may gradually regain their activity and volume, resulting in uneven, incomplete, and unsustainable fat reduction effects, which affect the overall shape and long-term stability of the final shaping.
[0003] To overcome the shortcomings of microwave heating efficiency and specificity, the concept of microwave sensitizing materials has been introduced. Microwave sensitizers, especially certain nanomaterials, possess the property of efficiently absorbing microwave energy and converting it into heat energy. Through specific delivery methods, it is hoped that these sensitizers can be relatively enriched in the target adipose region. When an external microwave field is applied, the region enriched with sensitizers should theoretically experience a more significant local temperature rise, thereby improving the specificity and efficiency of heating fat cells, reducing the thermal impact on surrounding tissues, and potentially enhancing the efficacy of a single treatment.
[0004] Currently, microwave sensitizing materials such as iron oxides, carbon nanomaterials, magnetic particles, and rare earth composites have been developed. However, the microwave sensitizing efficiency of these materials is relatively low, and their long-term biological toxicity and metabolic pathways are still unclear. They have poor biological safety and may induce inflammatory reactions or produce cytotoxicity in vivo, leading to damage to normal organisms, which limits their clinical translation and application.
[0005] Therefore, providing a microwave thermotherapy sensitizing material with good biosafety and high microwave sensitization efficiency has become a problem that needs to be solved. Summary of the Invention
[0006] In view of this, the technical problem to be solved by the present invention is to provide a microwave thermotherapy sensitizing polyamino acid material, its preparation method and application. The microwave thermotherapy sensitizing polyamino acid material provided by the present invention has good biosafety and high microwave sensitizing efficiency.
[0007] This invention provides a microwave thermotherapy-sensitizing polyamino acid material, wherein the polyamino acid material is selected from at least one of polyamino acids, polyamino acid salts, or polyethylene glycol-modified polyamino acids.
[0008] Preferably, the polyamino acid is selected from at least one of polyglutamic acid, polyaspartic acid, polyglutamic acid-phenylalanine random copolymer, polyglutamic acid-alanine random copolymer, polyglutamic acid-valine random copolymer, polyaspartic acid-alanine random copolymer, and polylysine-phenylalanine random copolymer.
[0009] Preferably, the degree of polymerization of the polyglutamic acid is 160-500;
[0010] The degree of polymerization of the polyaspartic acid is 160~300;
[0011] In the polyglutamic acid-phenylalanine random copolymer, the degree of polymerization of glutamic acid is 140-150, and the degree of polymerization of phenylalanine is 10-20.
[0012] In the polyglutamic acid-alanine random copolymer, the degree of polymerization of glutamic acid is 140-150, and the degree of polymerization of alanine is 10-20.
[0013] In the polyglutamic acid-valine random copolymer, the degree of polymerization of glutamic acid is 140-150, and the degree of polymerization of valine is 10-20.
[0014] In the polyaspartic acid-alanine random copolymer, the degree of polymerization of aspartic acid is 140-150 and the degree of polymerization of alanine is 10-20.
[0015] In the polylysine-phenylalanine random copolymer, the degree of polymerization of lysine is 45-55, and the degree of polymerization of phenylalanine is 2-10.
[0016] Preferably, the polyamino acid salt is selected from polyglutamate.
[0017] Preferably, the polyethylene glycol-modified polyamino acid is selected from at least one of polyethylene glycol-modified polyglutamic acid, polyethylene glycol-modified polyaspartic acid, polyethylene glycol-modified polyglutamic acid-phenylalanine random copolymer, polyethylene glycol-modified polyaspartic acid-alanine random copolymer, and polyethylene glycol-modified polyglutamic acid-alanine random copolymer.
[0018] The present invention also provides a method for preparing the above-mentioned microwave thermotherapy-sensitized polyamino acid material, wherein the method for preparing the polyamino acid includes the following steps:
[0019] Under the action of an initiator, the intracyclic anhydride of amino acids undergoes a ring-opening polymerization reaction to obtain polyamino acids;
[0020] The preparation method of the polyamino acid salt includes the following steps:
[0021] Polyamino acids are reacted with bicarbonates to obtain polyamino acid salts;
[0022] The method for preparing the polyethylene glycol-modified polyamino acid includes the following steps:
[0023] In the presence of a catalyst and a condensing agent, polyethylene glycol monomethyl ether and polyamino acids are mixed and reacted to obtain polyethylene glycol-modified polyamino acids.
[0024] Preferably, in the method for preparing the polyamino acid, the initiator is selected from at least one of primary amine initiators, secondary amine initiators, and alcohol / phenol initiators;
[0025] The molar ratio of the intracyclic anhydride of the amino acid to the initiator is 30:1 to 500:1.
[0026] Preferably, in the method for preparing the polyamino acid salt, the bicarbonate is selected from sodium bicarbonate.
[0027] Preferably, in the method for preparing the polyethylene glycol-modified polyamino acid, the catalyst is selected from 4-dimethylaminopyridine, and the condensing agent is selected from N,N'-diisopropylcarbodiimide;
[0028] The polyethylene glycol monomethyl ether has a weight-average molecular weight of 2000~10000;
[0029] The molar ratio of polyethylene glycol monomethyl ether to polyamino acid is 1:10 to 1:30.
[0030] The present invention also provides an application of the above-mentioned microwave thermotherapy-sensitized polyamino acid material in the preparation of microwave-molded microwave-sensitized materials.
[0031] Compared with existing technologies, this invention provides a microwave thermotherapy-sensitizing polyamino acid material, wherein the polyamino acid material is selected from at least one of polyamino acids, polyamino acid salts, or polyethylene glycol-modified polyamino acids. The polyamino acid material provided by this invention significantly increases the microwave heat generation temperature by 5-8°C compared to traditional methods, and utilizes the material's excellent biocompatibility to achieve highly efficient fat decomposition. This solves the core problems of low fat-dissolving efficiency and insufficient energy conversion rate in existing microwave lipolysis techniques, ultimately achieving the goal of reducing the number of treatments and improving clinical outcomes. Attached Figure Description
[0032] Figure 1 The microwave heat generation time-temperature curve of material 1 is shown.
[0033] Figure 2 The microwave heat generation time-temperature curve of material 2 is shown.
[0034] Figure 3 The microwave heat generation time-temperature curve of material 3 is shown.
[0035] Figure 4 The microwave heat generation time-temperature curve of material 4 is shown.
[0036] Figure 5 The microwave heat generation time-temperature curve of material 5 is shown.
[0037] Figure 6 The microwave heat generation time-temperature curve of material 6 is shown.
[0038] Figure 7 The microwave heat generation time-temperature curve of material 7 is shown.
[0039] Figure 8 The microwave heat generation time-temperature curve of material 8 is shown.
[0040] Figure 9 The microwave heat generation time-temperature curve of material 9 is shown.
[0041] Figure 10 The microwave heating time-temperature curve of material 10 is shown.
[0042] Figure 11 The microwave heat generation time-temperature curve of material 11 is shown.
[0043] Figure 12 The microwave heat generation time-temperature curve of material 12 is shown.
[0044] Figure 13 The microwave heat generation time-temperature curve of material 13 is shown.
[0045] Figure 14 Microwave thermal effects of materials 1-3 in fat;
[0046] Figure 15 Microwave thermal effects of materials 4-6 and the comparative high-entropy alloy in fat;
[0047] Figure 16 This is a microwave thermal effect diagram of material 7-13 in fat;
[0048] Figure 17The graph shows the highest temperature difference between materials 1-6 and high-entropy alloys in fat and physiological saline.
[0049] Figure 18 The graph shows the highest temperature difference between materials 7-13 in fat and physiological saline. Detailed Implementation
[0050] This invention provides a microwave thermotherapy-sensitizing polyamino acid material, wherein the polyamino acid material is selected from at least one of polyamino acids, polyamino acid salts, or polyethylene glycol-modified polyamino acids.
[0051] In some specific embodiments of the present invention, the polyamino acid is selected from at least one of polyglutamic acid, polyaspartic acid, polyglutamic acid-phenylalanine random copolymer, polyglutamic acid-alanine random copolymer, polyglutamic acid-valine random copolymer, polyaspartic acid-alanine random copolymer, and polylysine-phenylalanine random copolymer.
[0052] In this invention, the degree of polymerization of the polyglutamic acid is 160~500, and can be 160, 200, 250, 300, 350, 400, 450, 500, or any value between 160 and 500;
[0053] The degree of polymerization of the polyaspartic acid is 160~300, and can be 160, 180, 200, 250, 300, or any value between 160 and 300;
[0054] In the polyglutamic acid-phenylalanine random copolymer, the degree of polymerization of glutamic acid is 140~150, which can be 140, 145, 150, or any value between 140 and 150, and the degree of polymerization of phenylalanine is 10~20, which can be 10, 15, 20, or any value between 10 and 20.
[0055] In the polyglutamic acid-alanine random copolymer, the degree of polymerization of glutamic acid is 140~150, which can be 140, 145, 150, or any value between 140 and 150, and the degree of polymerization of alanine is 10~20, which can be 10, 15, 20, or any value between 10 and 20.
[0056] In the polyglutamic acid-valine random copolymer, the degree of polymerization of glutamic acid is 140~150, which can be 140, 145, 150, or any value between 140 and 150, and the degree of polymerization of valine is 10~20, which can be 10, 15, 20, or any value between 10 and 20.
[0057] In the polyaspartic acid-alanine random copolymer, the degree of polymerization of aspartic acid is 140~150, which can be 140, 145, 150, or any value between 140 and 150, and the degree of polymerization of alanine is 10~20, which can be 10, 15, 20, or any value between 10 and 20.
[0058] In the polylysine-phenylalanine random copolymer, the degree of polymerization of lysine is 45~55, which can be 45, 50, 55, or any value between 45 and 55, and the degree of polymerization of phenylalanine is 2~10, which can be 2, 5, 10, or any value between 2 and 10.
[0059] In this invention, the polyamino acid salt is selected from polyglutamate salt, and the polyglutamate salt is selected from sodium polyglutamate.
[0060] In this invention, the polyethylene glycol-modified polyamino acid is selected from at least one of polyethylene glycol-modified polyglutamic acid, polyethylene glycol-modified polyaspartic acid, polyethylene glycol-modified polyglutamic acid-phenylalanine random copolymer, polyethylene glycol-modified polyaspartic acid-alanine random copolymer, and polyethylene glycol-modified polyglutamic acid-alanine random copolymer.
[0061] In this invention, the polyamino acid material exhibits good heating effect during microwave treatment. In some preferred embodiments of this invention, the polyethylene glycol-modified polyglutamic acid-phenylalanine random copolymer, the polyethylene glycol-modified polyaspartic acid-alanine random copolymer, or the polyethylene glycol-modified polyglutamic acid-alanine random copolymer exhibits even better heating effect during microwave treatment.
[0062] The polyamino acid material provided by this invention has excellent thermal conversion capabilities and can be used in microwave thermotherapy to enhance the thermotherapy effect and achieve better treatment results.
[0063] In this invention, the polyamino acid material exhibits a certain effect in enhancing microwave heating in fats. In some preferred embodiments of this invention, the polyethylene glycol-modified polyglutamic acid, polyethylene glycol-modified polyaspartic acid, polyethylene glycol-modified polyglutamic acid-phenylalanine random copolymer, polyglutamic acid-valine random copolymer, polyaspartic acid-alanine random copolymer, and polyethylene glycol-modified polyaspartic acid-alanine random copolymer all demonstrate good microwave heating enhancement in fats. In some more preferred embodiments of this invention, the polyaspartic acid-alanine random copolymer exhibits an even more superior microwave heating enhancement effect in fats.
[0064] The polyamino acid material provided by this invention also has excellent microwave thermal conversion ability in fat, and can be applied in microwave fat reduction related fields to enhance fat melting effect and achieve better weight loss and body shaping.
[0065] The polyamino acid material provided by this invention significantly increases the microwave heat generation temperature by 5-8°C compared to traditional methods. It also utilizes the material's excellent biocompatibility to achieve efficient fat decomposition, thereby solving the core problems of low fat dissolving efficiency and insufficient energy conversion rate in existing microwave lipolysis technology. Ultimately, it aims to reduce the number of treatments and improve clinical outcomes.
[0066] This invention also provides a method for preparing the above-mentioned microwave thermotherapy-sensitized polyamino acid material. The method for preparing the polyamino acid includes the following steps:
[0067] Under the action of an initiator, the intracyclic anhydride of amino acids undergoes a ring-opening polymerization reaction to obtain polyamino acids.
[0068] Specifically, the initiator is selected from at least one of primary amine initiators, secondary amine initiators, and alcohol / phenol initiators. The primary amine initiator is preferably ethylamine, n-butylamine, hexylamine, ethanolamine, ethyl aminoethyl, etc.; the secondary amine initiator is preferably diethylamine, piperidine, morpholine, etc.; and the alcohol / phenol initiator is preferably methanol, ethanol, phenol, etc.
[0069] The molar ratio of the intracyclic anhydride of the amino acid to the initiator is 30:1 to 500:1, and can be any value between 30:1, 50:1, 100:1, 150:1, 200:1, 250:1, 300:1, 350:1, 400:1, 450:1, 500:1, or 30:1 to 500:1.
[0070] Following the ring-opening polymerization reaction, the reaction solution is post-treated to obtain the product. The present invention does not impose any particular limitation on the post-treatment method; any post-treatment method known to those skilled in the art is acceptable. Preferably, the post-treatment can be performed according to the following method:
[0071] After the reaction was complete, the reaction solution was slowly settled into diethyl ether, filtered to obtain a solid, washed with diethyl ether, and dried under vacuum. After drying, it was dissolved in 10 times its volume of trifluoroacetic acid. After complete dissolution, 33 wt% hydrobromic acid solution was added, and the reaction was stirred at room temperature. After the reaction was complete, it was slowly settled into diethyl ether, filtered to obtain a solid, washed twice with diethyl ether, and dried under vacuum. After drying, it was dissolved in DMF, dialyzed in a dialysis bag, and after dialysis, it was lyophilized to obtain the product.
[0072] Polyamino acids with different degrees of polymerization can be polymerized using the same method, only requiring a change in the feed ratio of hexylamine and the intracyclic anhydride of the amino acid.
[0073] The preparation method of the polyamino acid salt includes the following steps:
[0074] Polyamino acids are reacted with bicarbonates to obtain polyamino acid salts.
[0075] In this invention, the bicarbonate is selected from sodium bicarbonate.
[0076] After the reaction is completed, the reaction solution is dialyzed and dried to obtain the product.
[0077] The method for preparing the polyethylene glycol-modified polyamino acid includes the following steps:
[0078] In the presence of a catalyst and a condensing agent, polyethylene glycol monomethyl ether and polyamino acids are mixed and reacted to obtain polyethylene glycol-modified polyamino acids.
[0079] Specifically, the catalyst is selected from 4-dimethylaminopyridine, and the condensing agent is selected from N,N'-diisopropylcarbodiimide;
[0080] The polyethylene glycol monomethyl ether has a weight-average molecular weight of 2000 to 10000, and can be any value between 2000, 3000, 4000, 5000, 6000, 7000, 8000, 9000, 10000, or 2000 to 10000.
[0081] The molar ratio of polyethylene glycol monomethyl ether to polyamino acid is 1:10 to 1:30, and can be any value between 1:10, 1:15, 1:20, 1:25, 1:30, or 1:10 to 1:30.
[0082] After the reaction is complete, the reaction solution undergoes post-treatment. This invention does not impose any special limitations on the post-treatment method; any post-treatment method known to those skilled in the art is acceptable. Preferably, the post-treatment can be performed as follows:
[0083] After the reaction was completed, the reaction solution settled in diethyl ether, and the solid was obtained by filtration. The solid was dissolved in anhydrous DMF and settled in diethyl ether again. The solid was then filtered and dried under vacuum to obtain the product.
[0084] In this invention, polyethylene glycol-modified polyamino acids with different degrees of modification are processed using the same steps described above, only requiring changes to the molecular weight of polyethylene glycol monomethyl ether and the feeding ratio of polyethylene glycol monomethyl ether to polyamino acids.
[0085] The present invention also provides an application of the above-mentioned microwave thermotherapy-sensitized polyamino acid material in the preparation of microwave-molded microwave-sensitized materials.
[0086] The polyamino acid material provided by this invention can absorb and convert microwave energy, thereby enhancing the heat generation efficiency of microwaves per unit area. Due to its excellent biocompatibility, this polyamino acid material can be applied in the fields of microwave and radiofrequency fat reduction. Injecting it into the target fat reduction area improves microwave fat reduction efficiency while also addressing issues such as skin burns and damage to surrounding tissues.
[0087] This invention utilizes polyamino acid materials as microwave energy sensitizers, which possess microwave-sensitizing properties. Compared to existing technologies, this material exhibits superior biocompatibility, biodegradability, and highly efficient microwave energy conversion capabilities achieved through specific molecular design. Compared to existing technologies, this invention offers the following advantages:
[0088] First, the energy conversion rate mediated by materials is greatly increased, which significantly improves the efficiency of single fat dissolving.
[0089] Secondly, the precise temperature rise of 5~8℃ enhances the thermal decomposition of fat while ensuring the reliability of treatment due to the biosafety of the materials.
[0090] Third, it has made a breakthrough in solving the long-standing industry pain points of low energy utilization efficiency and insufficient heating of target tissues in the field of microwave lipolysis, providing a revolutionary solution for clinical use that combines high efficiency and safety.
[0091] To further understand the present invention, the following embodiments illustrate the microwave thermotherapy sensitizing polyamino acid material, its preparation method, and its application. The scope of protection of the present invention is not limited by the following embodiments.
[0092] Example 1: Preparation of Polyglutamic Acid
[0093] Select a suitable reaction flask and heat it, replacing the nitrogen atmosphere three times to ensure anhydrous and oxygen-free conditions. Weigh 8.3 g of glutamic acid-5-benzyl ester-N-carboxylic acid anhydride and add it to the flask. Vacuum for 30 min. In a glove box, add 1 g of 0.02 g / g n-hexylamine / N,N-dimethylformamide (DMF) solution. Add 100 ml of anhydrous DMF as the reaction solvent and react at room temperature for 3 days. After the reaction is complete, slowly settle the solid into 700 ml of diethyl ether, filter to obtain the solid, wash the solid twice with diethyl ether, and dry under vacuum. After drying, dissolve the solid in 80 ml of 10 times its volume of trifluoroacetic acid. After complete dissolution, add 24 ml of 33 wt% hydrobromic acid solution and stir at room temperature for 1.5 h. After the reaction is complete, slowly settle the solid into 700 ml of diethyl ether, filter to obtain the solid, wash the solid twice with diethyl ether, and dry under vacuum overnight. After drying, the product was dissolved in 80 ml of DMF, placed in a 7000 Da dialysis bag, and dialyzed for three days, with the water changed about 10 times during the process. After dialysis, the product was freeze-dried for three days to obtain polyglutamic acid with a degree of polymerization of 160.
[0094] Example 2 Preparation of polyaspartic acid
[0095] Select a suitable reaction flask and heat it, replacing the nitrogen atmosphere three times to ensure anhydrous and oxygen-free conditions. Weigh 7.9 g of aspartic acid-4-benzyl ester-N-carboxylic acid anhydride into the flask, evacuate for 30 min, and add 1 g of 0.02 g / g n-hexylamine / N,N-dimethylformamide (DMF) solution in a glove box. Add 100 ml of anhydrous DMF as the reaction solvent and react at room temperature for 3 days. After the reaction is complete, slowly settle the solid into 700 ml of diethyl ether, filter to obtain the solid, wash the solid twice with diethyl ether, and dry under vacuum. After drying, dissolve the solid in 80 ml of 10 times its volume of trifluoroacetic acid. After complete dissolution, add 24 ml of 33 wt% hydrobromic acid solution and stir at room temperature for 1.5 h. After the reaction is complete, slowly settle the solid into 700 ml of diethyl ether, filter to obtain the solid, wash the solid twice with diethyl ether, and dry under vacuum overnight. After drying, the product was dissolved in 80 ml of DMF, placed in a 7000 Da dialysis bag, and dialyzed for three days, with the water changed about 10 times during the period. After dialysis, the product was freeze-dried for three days to obtain polyaspartic acid with a degree of polymerization of 160.
[0096] Example 3 Preparation of polyglutamic acid-phenylalanine random copolymer
[0097] Select a suitable-sized reaction flask and heat it, replacing the nitrogen atmosphere three times to ensure anhydrous and oxygen-free conditions. Weigh 7.8 g of glutamic acid-5-benzyl ester-N-carboxylic acid anhydride and 0.38 g of L-phenylalanine-N-carboxylic acid anhydride into the flask, evacuate the vacuum for 30 min, and add 1 g of 0.02 g / g n-hexylamine / N,N-dimethylformamide (DMF) solution in a glove box. Add 100 ml of anhydrous DMF as the reaction solvent and react at room temperature for 3 days. After the reaction is complete, slowly settle the solid into 700 ml of diethyl ether, filter it to obtain a solid, wash the solid twice with diethyl ether, and dry it under vacuum. After drying, dissolve it in 80 ml of 10 times its volume of trifluoroacetic acid. After complete dissolution, add 24 ml of 33 wt% hydrobromic acid solution and stir the reaction at room temperature for 1.5 h. After the reaction is complete, slowly settle the solid into 700 ml of diethyl ether, filter it to obtain a solid, wash the solid twice with diethyl ether, and dry it under vacuum overnight. After drying, the solution was dissolved in 80 ml of DMF, placed in a 7000 Da dialysis bag, and dialyzed for three days, changing the water approximately 10 times during this period. After dialysis, the solution was freeze-dried for three days to obtain the product, a polyglutamic acid-phenylalanine random copolymer. The degree of polymerization of glutamic acid was 150, and that of phenylalanine was 10.
[0098] Example 4 Preparation of polyethylene glycol-modified polyglutamic acid
[0099] 4 g of polyglutamic acid with a degree of polymerization of 160 was weighed and added to a round-bottom flask. 8 g of polyethylene glycol monomethyl ether with an average molecular weight of 5000 was added, and dissolved in 100 ml of anhydrous DMF. Then, 0.58 g of 4-dimethylaminopyridine (DMAP) was added, followed by 0.4 g of N,N'-diisopropylcarbodiimide (DIC) at 4°C. The reaction was carried out at room temperature for 48 h. After the reaction was complete, the product precipitated in diethyl ether and filtered to obtain a solid. The solid was dissolved in anhydrous DMF and then precipitated in diethyl ether again. The solid was filtered again and dried under vacuum to obtain the product, polyethylene glycol-modified polyglutamic acid.
[0100] Example 5 Preparation of polyethylene glycol-modified polyaspartic acid
[0101] 4 g of polyaspartic acid with a degree of polymerization of 160 was weighed and added to a round-bottom flask. 9.2 g of polyethylene glycol monomethyl ether with an average molecular weight of 5000 was added, and dissolved in 100 ml of anhydrous DMF. Then, 0.667 g of 4-dimethylaminopyridine (DMAP) was added, followed by 0.46 g of N,N'-diisopropylcarbodiimide (DIC) at 4 °C. The reaction was carried out at room temperature for 48 h. After the reaction was complete, the product precipitated in diethyl ether and filtered to obtain a solid. The solid was dissolved in anhydrous DMF and then precipitated in diethyl ether again. The solid was filtered again and dried under vacuum to obtain the product, polyethylene glycol-modified polyaspartic acid.
[0102] Example 6 Preparation of polyethylene glycol-modified polyglutamic acid-phenylalanine random copolymer
[0103] 4 g of a random copolymer of glutamic acid (degree of polymerization 150) and phenylalanine (degree of polymerization 10) was weighed and added to a round-bottom flask. 8 g of polyethylene glycol monomethyl ether (PEG) with an average molecular weight of 5000 was added, and the copolymer was dissolved in 100 ml of anhydrous DMF. Then, 0.58 g of 4-dimethylaminopyridine (DMAP) was added, followed by 0.4 g of N,N'-diisopropylcarbodiimide (DIC) at 4°C. The reaction was carried out at room temperature for 48 h. After the reaction was complete, the copolymer precipitated in diethyl ether and filtered to obtain a solid. The solid was dissolved in anhydrous DMF and then precipitated in diethyl ether again. The solid was then filtered and dried under vacuum to obtain the product: a polyethylene glycol-modified polyglutamic acid-phenylalanine random copolymer.
[0104] Example 7 Preparation of polyglutamic acid-alanine random copolymer
[0105] Weigh 7.8 g of glutamic acid-5-benzyl ester-N-carboxycyclic anhydride Glu(Obzl)-NCA and 0.23 g of alanine-N-carboxycyclic anhydride monomer into a flask, evacuate for 30 min, and add 1 g of a 0.02 g / g n-hexylamine / N,N-dimethylformamide (DMF) solution. Add 100 ml of anhydrous DMF as the reaction solvent and react at room temperature for 3 days. After the reaction is complete, slowly settle into 700 ml of diethyl ether, filter to obtain a solid, wash the solid twice with diethyl ether, and dry under vacuum. After drying, dissolve it in 80 ml of 10 times its volume of trifluoroacetic acid. After complete dissolution, add 24 ml of 33 wt% hydrobromic acid solution and stir at room temperature for 1.5 h. After the reaction is complete, slowly settle into 700 ml of diethyl ether, filter to obtain a solid, wash the solid twice with diethyl ether, and dry under vacuum overnight. After drying, the product was dissolved in 80 ml of DMF, placed in a 7000 Da dialysis bag, and dialyzed for three days, with the water changed about 10 times during the period. After dialysis, the product was freeze-dried for three days to obtain a polyglutamic acid-alanine random copolymer, in which the degree of polymerization of glutamic acid was 150 and the degree of polymerization of phenylalanine was 10.
[0106] Example 8 Preparation of polyglutamic acid-valine random copolymer
[0107] Weigh 7.8 g of glutamic acid-5-benzyl ester-N-carboxycyclic anhydride Glu(Obzl)-NCA and 0.28 g of valine N-carboxycyclic anhydride monomer into a flask, evacuate for 30 min, and add 1 g of a 0.02 g / g n-hexylamine / N,N-dimethylformamide (DMF) solution. Add 100 ml of anhydrous DMF as the reaction solvent and react at room temperature for 3 days. After the reaction is complete, slowly settle the solid into 700 ml of diethyl ether, filter to obtain a solid, wash the solid twice with diethyl ether, and dry under vacuum. After drying, dissolve the solid in 80 ml of 10 times its volume of trifluoroacetic acid. After complete dissolution, add 24 ml of 33 wt% hydrobromic acid solution and stir at room temperature for 1.5 h. After the reaction is complete, slowly settle the solid into 700 ml of diethyl ether, filter to obtain a solid, wash the solid twice with diethyl ether, and dry under vacuum overnight. After drying, the product was dissolved in 80 ml of DMF, placed in a 7000 Da dialysis bag, and dialyzed for three days, with the water changed about 10 times during the period. After dialysis, the product was freeze-dried for three days to obtain a polyglutamic acid-valine random copolymer, in which the degree of polymerization of glutamic acid was 150 and the degree of polymerization of valine was 10.
[0108] Example 9 Preparation of polyaspartic acid-alanine random copolymer
[0109] Weigh 7.38 g of aspartic acid-4-benzyl ester-N-carboxylic acid anhydride monomer and 0.23 g of alanine-N-carboxylic acid anhydride monomer into a flask, evacuate for 30 min, and add 1 g of 0.02 g / g n-hexylamine / N,N-dimethylformamide (DMF) solution. Add 100 ml of anhydrous DMF as the reaction solvent and react at room temperature for 3 days. After the reaction is complete, slowly settle into 700 ml of diethyl ether, filter to obtain a solid, wash the solid twice with diethyl ether, and dry under vacuum. After drying, dissolve it in 80 ml of 10 times its volume of trifluoroacetic acid. After complete dissolution, add 24 ml of 33 wt% hydrobromic acid solution and stir at room temperature for 1.5 h. After the reaction is complete, slowly settle into 700 ml of diethyl ether, filter to obtain a solid, wash the solid twice with diethyl ether, and dry under vacuum overnight. After drying, the product was dissolved in 80 ml of DMF, placed in a 7000 Da dialysis bag, and dialyzed for three days, with the water changed about 10 times during the period. After dialysis, the product was freeze-dried for three days to obtain a polyaspartic acid-alanine random copolymer, in which the degree of polymerization of glutamic acid was 150 and the degree of polymerization of phenylalanine was 10.
[0110] Example 10 Preparation of polyethylene glycol-modified polyaspartic acid-alanine random copolymer
[0111] 4g of the polyaspartic acid-alanine random copolymer prepared in Example 9 was weighed and added to a round-bottom flask. 8.8g of polyethylene glycol monomethyl ether with an average molecular weight of 5000 was added, and 100ml of anhydrous DMF was added to dissolve it. Then, 0.637g of 4-dimethylaminopyridine (DMAP) was added, followed by 0.44g of N,N'-diisopropylcarbodiimide (DIC) at 4°C. The reaction was carried out at room temperature for 48h. After the reaction was complete, the product precipitated in diethyl ether and was filtered to obtain a solid. The solid was dissolved in anhydrous DMF and then precipitated in diethyl ether again. The solid was filtered again and dried under vacuum to obtain the product: polyethylene glycol-modified polyaspartic acid-alanine random copolymer.
[0112] Example 11 Preparation of polyethylene glycol-modified polyglutamic acid-alanine random copolymer
[0113] 4g of the polyglutamic acid-alanine random copolymer prepared in Example 7 was weighed and added to a round-bottom flask. 7.9g of polyethylene glycol monomethyl ether with an average molecular weight of 5000 was added, and 100ml of anhydrous DMF was added to dissolve it. Then, 0.57g of 4-dimethylaminopyridine (DMAP) was added, followed by 0.4g of N,N'-diisopropylcarbodiimide (DIC) at 4°C. The reaction was carried out at room temperature for 48h. After the reaction was complete, the product precipitated in diethyl ether and was filtered to obtain a solid. The solid was dissolved in anhydrous DMF and then precipitated in diethyl ether again. The solid was filtered again and dried under vacuum to obtain the product: polyethylene glycol-modified polyglutamic acid-alanine random copolymer.
[0114] Example 12 Preparation of polylysine-phenylalanine random copolymer
[0115] Weigh 1.51 g of N6-benzyloxycarbonyl-L-lysine ring anhydride monomer and 0.09 g of L-phenylalanine-N-carboxyl ring anhydride monomer and add them to a flask. Vacuum the mixture for 30 min, then add 0.5 g of a 0.02 g / g n-hexylamine / N,N-dimethylformamide (DMF) solution. Add 20 ml of anhydrous DMF as the reaction solvent and react at room temperature for 3 days. After the reaction is complete, slowly settle the solid into 200 ml of diethyl ether, filter, wash twice with diethyl ether, and dry under vacuum. After drying, dissolve the solid in 15 ml of 10 times its volume of trifluoroacetic acid. After complete dissolution, add 4.5 ml of 33 wt% hydrobromic acid solution and stir at room temperature for 1.5 h. After the reaction is complete, slowly settle the solid into 150 ml of diethyl ether, filter, wash twice with diethyl ether, and dry under vacuum overnight. After drying, the product was dissolved in 15 ml of DMF, placed in a 7000 Da dialysis bag, and dialyzed for three days, with the water changed about 10 times during the period. After dialysis, the product was freeze-dried for three days to obtain polylysine-phenylalanine random copolymer, in which the degree of polymerization of lysine was 50 and the degree of polymerization of phenylalanine was 5.
[0116] Example 13 Preparation of Sodium Polyglutamate
[0117] Weigh 4g of the polyglutamic acid material with a degree of polymerization of 160 prepared above and add it to a beaker. Add 60ml of water and disperse evenly. Then slowly add saturated sodium bicarbonate solution dropwise until no more bubbles are produced and the pH is maintained at around 8.3 for 10 minutes. Then place it in a 3500Da dialysis bag and dialyze with water for 12 hours, changing the water 6 times during the process. After dialysis, freeze-dry the product, sodium polyglutamate, in a lyophilizer to obtain the product.
[0118] The materials prepared in Examples 1 to 13 are named Materials 1-13, respectively.
[0119] Test Example 1: In vitro microwave thermal effect experiment of polyamino acid materials
[0120] Polyamino acid materials were dissolved and dispersed in 1 mL of physiological saline at different concentrations. Then, the solutions were irradiated with microwaves at 1.8 W and 433 Hz for 5 minutes. During the experiment, the temperature of the experimental solutions was monitored in real time using a FLIR infrared imaging instrument, with temperature values recorded every 10 seconds, and time-temperature curves were plotted. Figures 1 to 13It can be seen that all the prepared polyamino acid materials enhance microwave heat generation, and the heating effect of the polyamino acid materials is significantly greater than that of physiological saline. Materials 6, 10, and 11 have even better heating effects, with the maximum temperature increased by 7.0℃, 6.8℃, and 6.5℃ respectively compared to physiological saline. Therefore, polyamino acid materials have excellent heat conversion capabilities and can be used in microwave hyperthermia-related fields to enhance the hyperthermic effect and achieve better therapeutic results.
[0121] Test Example 2: Microwave Thermal Effect Experiment of Polyamino Acid Materials in Fats
[0122] Polyamino acid material was dissolved in physiological saline at a concentration of 5 mg / ml. Pork fat was used, and 0.5 ml of the material solution was injected evenly into the fat. Microwave irradiation was then applied, and temperature changes were recorded every 30 seconds using the aforementioned infrared monitor. Results are shown below. Figures 14-18 As shown in Table 1, the experimental results indicate that, except for materials 2, 12, and 13, other polyamino acid materials also exhibit a certain degree of enhanced microwave heating effect in fat. Materials 4, 5, 6, 8, 9, and 10 show higher microwave heating effects than the high-entropy alloy materials in existing studies, with material 9 showing the highest heating effect, increasing the temperature by up to 10.7℃ compared to physiological saline. This demonstrates that polyamino acid materials also possess excellent microwave thermal conversion capabilities in fat and can be applied in microwave fat reduction fields to enhance fat melting effects and achieve better weight loss and body shaping.
[0123] Table 1. Temperature changes of various materials in fat compared to physiological saline.
[0124]
[0125] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.
Claims
1. A polyamino acid material for microwave thermotherapy sensitization, characterized in that, The polyamino acid material is selected from at least one of polyamino acids, polyamino acid salts, or polyethylene glycol-modified polyamino acids.
2. The polyamino acid material according to claim 1, characterized in that, The polyamino acid is selected from at least one of polyglutamic acid, polyaspartic acid, polyglutamic acid-phenylalanine random copolymer, polyglutamic acid-alanine random copolymer, polyglutamic acid-valine random copolymer, polyaspartic acid-alanine random copolymer, and polylysine-phenylalanine random copolymer.
3. The polyamino acid material according to claim 2, characterized in that, The degree of polymerization of the polyglutamic acid is 160~500; The degree of polymerization of the polyaspartic acid is 160~300; In the polyglutamic acid-phenylalanine random copolymer, the degree of polymerization of glutamic acid is 140-150, and the degree of polymerization of phenylalanine is 10-20. In the polyglutamic acid-alanine random copolymer, the degree of polymerization of glutamic acid is 140-150, and the degree of polymerization of alanine is 10-20. In the polyglutamic acid-valine random copolymer, the degree of polymerization of glutamic acid is 140-150, and the degree of polymerization of valine is 10-20. In the polyaspartic acid-alanine random copolymer, the degree of polymerization of aspartic acid is 140-150 and the degree of polymerization of alanine is 10-20. In the polylysine-phenylalanine random copolymer, the degree of polymerization of lysine is 45-55, and the degree of polymerization of phenylalanine is 2-10.
4. The polyamino acid material according to claim 1, characterized in that, The polyamino acid salt is selected from polyglutamate.
5. The polyamino acid material according to claim 1, characterized in that, The polyethylene glycol-modified polyamino acid is selected from at least one of polyethylene glycol-modified polyglutamic acid, polyethylene glycol-modified polyaspartic acid, polyethylene glycol-modified polyglutamic acid-phenylalanine random copolymer, polyethylene glycol-modified polyaspartic acid-alanine random copolymer, and polyethylene glycol-modified polyglutamic acid-alanine random copolymer.
6. A method for preparing a microwave thermotherapy-sensitizing polyamino acid material as described in any one of claims 1 to 5, characterized in that, The preparation method of the polyamino acid includes the following steps: Under the action of an initiator, the intracyclic anhydride of amino acids undergoes a ring-opening polymerization reaction to obtain polyamino acids; The preparation method of the polyamino acid salt includes the following steps: Polyamino acids are reacted with bicarbonates to obtain polyamino acid salts; The method for preparing the polyethylene glycol-modified polyamino acid includes the following steps: In the presence of a catalyst and a condensing agent, polyethylene glycol monomethyl ether and polyamino acids are mixed and reacted to obtain polyethylene glycol-modified polyamino acids.
7. The preparation method according to claim 6, characterized in that, In the preparation method of the polyamino acid, the initiator is selected from at least one of primary amine initiators, secondary amine initiators, and alcohol / phenol initiators; The molar ratio of the intracyclic anhydride of the amino acid to the initiator is 30:1 to 500:
1.
8. The preparation method according to claim 6, characterized in that, In the preparation method of the polyamino acid salt, the bicarbonate salt is selected from sodium bicarbonate.
9. The preparation method according to claim 6, characterized in that, In the method for preparing the polyethylene glycol-modified polyamino acid, the catalyst is selected from 4-dimethylaminopyridine, and the condensing agent is selected from N,N'-diisopropylcarbodiimide; The polyethylene glycol monomethyl ether has a weight-average molecular weight of 2000~10000; The molar ratio of polyethylene glycol monomethyl ether to polyamino acid is 1:10 to 1:
30.
10. The application of a microwave thermotherapy-sensitizing polyamino acid material as described in any one of claims 1 to 5 in the preparation of microwave-molded microwave-sensitizing materials.