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CN-121971375-A - Chitosan-beta-glycerophosphate temperature-sensitive material and preparation method and application thereof

CN121971375ACN 121971375 ACN121971375 ACN 121971375ACN-121971375-A

Abstract

The invention discloses a chitosan-beta-glycerophosphate temperature-sensitive material, a preparation method and application thereof, belonging to the technical field of pharmaceutical preparation and nano delivery, wherein the chitosan-beta-glycerophosphate temperature-sensitive material is formed by combining amino groups of chitosan and phosphate groups of beta-glycerophosphate through hydrogen bond interaction, A copper-doped Prussian blue composite temperature-sensitive hydrogel consists of copper-doped Prussian Lan Guangre catalytic nanoparticles loaded with tripterine and chitosan-beta-glycerophosphate temperature-sensitive materials. The composite temperature-sensitive hydrogel is in a liquid state under the low-temperature condition, and can quickly undergo sol-gel transition at physiological temperature, so as to realize in-situ gel formation. The composite hydrogel prepared by the invention has good injectability and biocompatibility, copper doped Prussian blue shows photo-thermal performance under near infrared light irradiation, and active oxygen species can be generated through the participation of copper ions in catalytic reaction, so that the enhancement of tumor treatment effect is realized by cooperation with the chemotherapy effect of tripterine.

Inventors

  • YUAN YUE
  • YANG ZHAOFEI

Assignees

  • 沈阳药科大学

Dates

Publication Date
20260505
Application Date
20260206

Claims (10)

  1. 1. The chitosan-beta-glycerophosphate temperature-sensitive material is characterized by being formed by combining amino groups of chitosan and phosphate groups of beta-glycerophosphate through hydrogen bond interaction.
  2. 2. A method for preparing the chitosan-beta-glycerophosphate temperature-sensitive material of claim 1, comprising the steps of: And dissolving chitosan in a 0.05-0.15M hydrochloric acid solution to prepare a chitosan solution, dissolving beta-glycerophosphate in deionized water to prepare a beta-glycerophosphate solution, dropwise adding the beta-glycerophosphate solution into the chitosan solution, and placing the mixture in an environment of 34-39 ℃ after stirring to form the chitosan-beta-glycerophosphate temperature-sensitive material.
  3. 3. The preparation method of the chitosan-beta-glycerophosphate temperature-sensitive material is characterized in that the concentration of the chitosan solution is 1% -3%, the concentration of the beta-glycerophosphate solution is 50% -65%, the volume ratio of the chitosan solution to the beta-glycerophosphate solution is (8-12): 1, the temperature of the beta-glycerophosphate solution is 2-6 ℃ when the beta-glycerophosphate solution is added into the chitosan solution drop by drop, and the stirring time of the mixture is 10-30 minutes.
  4. 4. The copper-doped Prussian blue composite temperature-sensitive hydrogel is characterized by comprising copper-doped Prussian Lan Guangre catalytic nanoparticles loaded with tripterine and the chitosan-beta-glycerophosphate temperature-sensitive material prepared by the chitosan-beta-glycerophosphate temperature-sensitive material or the chitosan-beta-glycerophosphate temperature-sensitive material prepared by the preparation method of claim 2 or 3, wherein in the copper-doped Prussian blue composite temperature-sensitive hydrogel, the concentration of chitosan is 1% -3%, the concentration of beta-glycerophosphate is 4% -6%, and the concentration of copper-doped Prussian Lan Guangre catalytic nanoparticles loaded with tripterine is 1.7 mg/mL-2.3 mg/mL.
  5. 5. The copper-doped Prussian-blue composite thermosensitive hydrogel according to claim 4, wherein the tripterine is loaded inside the copper-doped Prussian Lan Guangre catalytic nanoparticle.
  6. 6. A method for preparing the copper-doped Prussian blue composite temperature-sensitive hydrogel according to claim 4 or 5, which is characterized by comprising the following steps: Step1, preparation of copper-doped Prussian Lan Guangre catalytic nanoparticles Dissolving polyvinylpyrrolidone in hydrochloric acid solution, adding potassium ferricyanide for stirring reaction, centrifuging after finishing, collecting a product, washing and drying to obtain Prussian blue nanoparticles, mixing the Prussian blue nanoparticles, copper acetate, sodium citrate dihydrate and polyvinylpyrrolidone, stirring for reaction, then adding potassium ferricyanide, continuing to react the mixture, centrifuging after finishing, washing and separating to obtain copper-doped Prussian Lan Guangre catalytic nanoparticles; step 2, preparation of copper-doped Prussian Lan Guangre catalytic nanoparticles loaded with tripterine Dispersing the copper-doped Prussian Lan Guangre catalytic nanoparticles in ethanol, adding tripterine, stirring under dark conditions, and centrifuging after the completion to obtain copper-doped Prussian Lan Guangre catalytic nanoparticles loaded with the tripterine; step 3, preparation of copper-doped Prussian blue composite temperature-sensitive hydrogel Adding the copper-doped Prussian Lan Guangre catalytic nanoparticles loaded with tripterine into a chitosan solution, stirring and mixing uniformly, then dropwise adding a beta-glycerophosphate solution, stirring the mixture, placing the mixture in an environment of 34-39 ℃, and freeze-drying to obtain the copper-doped Prussian blue composite temperature-sensitive hydrogel.
  7. 7. The preparation method of the copper-doped Prussian blue composite thermosensitive hydrogel is characterized by comprising the following steps of 1,1 (3-5) of polyvinylpyrrolidone and potassium ferricyanide, 3-5 (3-20) of polyvinylpyrrolidone in hydrochloric acid solution, 3-5 (3-5) of potassium ferricyanide, 2-6 hours of reaction time, 10000 rpm~12000 rpm of centrifugal separation speed and 15-20 minutes of centrifugal separation speed, wherein a solvent used in a washing process is water or ethanol, and Prussian blue nanoparticles, copper acetate, sodium citrate dihydrate and polyvinylpyrrolidone react with potassium ferricyanide to obtain copper-doped Prussian Lan Guangre catalytic nanoparticles.
  8. 8. The preparation method of the copper-doped Prussian blue composite temperature-sensitive hydrogel is characterized in that in the step 2, the mass ratio of copper-doped Prussian Lan Guangre catalytic nanoparticles to tripterine is 1 (0.5-2), the stirring time is 18-48 hours, the centrifugal speed is 10000 rpm~12000 rpm, the centrifugal time is 5-15 minutes, the concentration of chitosan solution is 1% -3%, the concentration of beta-glycerophosphate solution is 50% -65%, the volume ratio of the chitosan solution to the beta-glycerophosphate solution is (8-12): 1, the temperature when the beta-glycerophosphate solution is dropwise added to the chitosan solution is 2-6 ℃, and the stirring time of the mixture is 10-30 minutes.
  9. 9. Application of the chitosan-beta-glycerophosphate temperature-sensitive material of claim 1 or 2 or the copper-doped Prussian blue composite temperature-sensitive hydrogel of claim 4 or 5 or the copper-doped Prussian blue composite temperature-sensitive hydrogel prepared by the preparation method of any one of claims 6 to 8 in preparation of anti-tumor products.
  10. 10. The use according to claim 9, wherein the tumor is a tumor of breast tissue.

Description

Chitosan-beta-glycerophosphate temperature-sensitive material and preparation method and application thereof Technical Field The invention belongs to the technical field of pharmaceutical preparations and nano delivery, and particularly relates to a copper-doped Prussian blue composite temperature-sensitive hydrogel based on a chitosan-beta-glycerophosphate temperature-sensitive material, and a preparation method and application thereof. Background Tumors are serious diseases seriously endangering the life health of human beings, and the treatment modes aiming at the tumors in clinic at present mainly comprise operation treatment, radiation treatment, chemotherapy and the like. The treatment mode can inhibit the growth of tumors to a certain extent, but still has the problems of insufficient treatment targeting, large damage to normal tissues, obvious systemic toxic and side effects and the like, and particularly in the treatment of solid tumors, the single treatment mode often has difficulty in obtaining ideal curative effects. Tumor tissue has special microenvironment characteristics different from normal tissue, such as weak acidic environment, excessive hydrogen peroxide accumulation, hypoxia state, etc., and the microenvironment has certain limitation on the curative effect of traditional therapeutic means while promoting tumor growth. Therefore, the development of tumor local treatment strategies around tumor microenvironment features is becoming an important direction of tumor treatment research. Photothermal therapy (PTT) is a treatment mode which utilizes a photothermal conversion material to generate a local thermal effect under the irradiation of near infrared light so as to induce the damage or death of tumor cells, has the advantages of minimally invasive property, space controllability and the like, but the complete elimination of tumor tissues is difficult to realize under the condition of low temperature or insufficient irradiation by single photothermal treatment. Chemical kinetics therapy (CDT) is a treatment strategy for generating active oxygen species by utilizing hydrogen peroxide in tumor microenvironment under the catalysis of metal ions or enzyme-like materials, so that oxidative damage is generated on tumor cells, but the catalysis efficiency is easily limited by the tumor microenvironment conditions. Prussian Blue (PB) has good biocompatibility and photo-thermal conversion performance, and can further endow Fenton-like catalytic activity through metal ion doping, wherein copper ions are paid attention to by having higher reactivity. The local administration technology is helpful for improving the tumor treatment efficiency and reducing the toxic and side effects of the system. The temperature-sensitive hydrogel has good application prospect in local tumor treatment due to injectability and in-situ gel forming characteristics. The chitosan and the beta-glycerophosphate can form a temperature-sensitive system, so that the material is gelled at physiological temperature, and the fixation and the slow release of the functional material at the tumor position are realized. However, the application of the existing temperature-sensitive hydrogel system in tumor treatment is still mainly single function, and the comprehensive performance of the existing temperature-sensitive hydrogel system in the aspects of cooperative photo-thermal treatment, chemical power treatment and tumor microenvironment regulation is still limited. The multifunctional nanomaterial is effectively loaded in a temperature-sensitive hydrogel system, and stable retention and cooperative treatment are realized on the tumor part, so that a certain technical challenge is still faced. Therefore, a composite hydrogel system which has good biocompatibility and Wen Mincheng gel performance and can integrate various tumor treatment functions is constructed, and the composite hydrogel system has important research significance and application value. Disclosure of Invention Aiming at the defects of the prior art, the invention aims to provide a preparation method and application of copper-doped Prussian blue composite temperature-sensitive hydrogel. The invention provides a copper-doped Prussian blue nanomaterial with photothermal conversion performance and Fenton-like catalytic activity, which is combined with a chitosan-beta-glycerophosphate temperature-sensitive hydrogel system to construct a composite hydrogel system capable of forming gel in situ under a physiological temperature condition. The composite temperature-sensitive hydrogel system constructed by the invention can combine multiple action modes such as photothermal therapy and chemical kinetic therapy, realizes local multi-mode cooperative therapy of tumor parts by utilizing the micro-environmental characteristics of tumors, and provides a new technical approach for local therapy of solid tumors while reducing systemic toxic and side effects. In order to achieve th