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CN-121971372-A - Quercetin-polypeptide co-assembled nano hydrogel and preparation method and application thereof

CN121971372ACN 121971372 ACN121971372 ACN 121971372ACN-121971372-A

Abstract

The invention discloses a quercetin-polypeptide co-assembled nano hydrogel, which belongs to the biomedical technology, and comprises quercetin and polypeptide in a mass ratio of 1:1-6, wherein the molecular formula of the polypeptide is R-G D F D F D Y, D , the amino acid is in a D configuration, R is a nonsteroidal anti-inflammatory drug, and the polypeptide has excellent self-assembly characteristics. According to the invention, the self-assembled polypeptide and the quercetin are co-assembled to form the quercetin-polypeptide co-assembled nano hydrogel, so that the solubility and stability of the quercetin are improved. The quercetin-polypeptide co-assembled nano hydrogel provided by the invention can be applied to preparation of ulcerative colitis medicines.

Inventors

  • LI XINXIN
  • HUANG GUANGRUI
  • JIANG HAIXU
  • TIAN YINGQI

Assignees

  • 北京中医药大学

Dates

Publication Date
20260505
Application Date
20251230

Claims (9)

  1. 1. The quercetin-polypeptide co-assembled nano hydrogel is characterized by comprising quercetin and polypeptide in a mass ratio of 1:1-6, wherein the molecular formula of the polypeptide is R-G D F D F D Y, D , the amino acid is in a D configuration, and R is a nonsteroidal anti-inflammatory drug.
  2. 2. The method for preparing the quercetin-polypeptide co-assembled nano-hydrogel according to claim 1, comprising the following steps: adding phosphate buffer solution into polypeptide, heating until the polypeptide is completely dissolved, adjusting the pH to 7-8, and standing at room temperature to form gel to obtain polypeptide hydrogel; adding phosphate buffer solution into the quercetin Pi Suzhong, heating until the quercetin is completely dissolved, and regulating the pH to 7-8 to obtain a quercetin Pi Sure solution; and thirdly, adding a quercetin Pi Sure solution into the polypeptide hydrogel, adding a phosphate buffer solution with pH of 7.4, heating to slight boiling, and standing at room temperature to form gel, thus obtaining the quercetin-polypeptide co-assembled nano hydrogel.
  3. 3. The method for preparing the quercetin-polypeptide co-assembled nano-hydrogel according to claim 2, wherein the polypeptide comprises a non-steroidal anti-inflammatory drug, a short peptide G D F D F D Y.
  4. 4. A method of preparing a quercetin-polypeptide co-assembled nano-hydrogel according to claim 3, wherein the method of preparing the polypeptide comprises the steps of: s1, dissolving N- (9-fluorenylmethoxycarbonyl) -O-tertiary butyl-D-tyrosine by using methylene dichloride, adding diisopropylethylamine, and mixing to obtain a reaction liquid I; S2, fully swelling the 2-Cl-Trt resin by adopting anhydrous dichloromethane, removing the dichloromethane, adding the reaction liquid I into a solid-phase synthesizer, reacting on a shaking table at room temperature, and obtaining a mixture 1 after the reaction is finished; s3, removing liquid in the mixture 1, washing for a plurality of times by adopting anhydrous dichloromethane, adding a sealing liquid, reacting on a shaking table at room temperature, and obtaining a mixture 2 after the reaction is finished, wherein the sealing liquid comprises dichloromethane, N diisopropylethylamine, methanol=17:1:2; S4, removing liquid in the mixture 2, sequentially adopting anhydrous dichloromethane and N, N-dimethylformamide to wash for a plurality of times, then adding a piperidine solution, reacting at room temperature, removing the liquid after the reaction is finished, and adopting N, N-dimethylformamide to wash for a plurality of times, wherein the solvent of the piperidine solution is N, N-dimethylformamide; S5, adding O-benzotriazole-tetramethyl urea hexafluorophosphate, diisopropylethylamine and N, N-dimethylformamide into N- (9-fluorenylmethoxycarbonyl) -D-phenylalanine, dissolving to obtain a reaction solution II, adding the reaction solution II into the solid phase washed in the step four, and reacting in a solid phase synthesizer until the reaction is finished; S6, repeating the step S4 and the step S5, sequentially adding N- (9-fluorenylmethoxycarbonyl) -L-phenylalanine and N- (9-fluorenylmethoxycarbonyl) -glycine, washing for a plurality of times by adopting N, N-dimethylformamide after the last amino acid is grafted, adding a piperidine solution for room temperature reaction, removing liquid after the reaction is finished, and washing for a plurality of times by adopting N, N-dimethylformamide to obtain a short peptide G D F D F D Y; S7, adding a peptide coupling reagent HBTU, diisopropylethylamine and N, N-dimethylformamide into a non-steroidal anti-inflammatory drug, dissolving to obtain a reaction solution III, reacting the reaction solution III with a short peptide G D F D F D Y in a solid-phase synthesizer, removing the liquid after the reaction is finished, and then respectively washing for a plurality of times by adopting the N, N-dimethylformamide and anhydrous dichloromethane in sequence; s8, adding a cutting fluid into a solid-phase synthesizer to cut R-G D F D F D Y from 2-Cl-Trt resin, concentrating and drying to obtain a crude product, and purifying the crude product to obtain the polypeptide.
  5. 5. The method for preparing quercetin-polypeptide co-assembled nano-hydrogel according to claim 2, wherein the solution for adjusting the pH in the first and second steps is sodium carbonate solution with a concentration of 1 mol/L.
  6. 6. The method for preparing quercetin-polypeptide co-assembled nano-hydrogel according to claim 2, wherein the concentration of the polypeptide hydrogel in the third step is 1-6 mg/mL, the concentration of the quercetin Pi Sure solution is 0.1-1 mg/mL, and the volume ratio of the polypeptide hydrogel to the quercetin Pi Sure solution is 1:1-2.
  7. 7. The method for preparing quercetin-polypeptide co-assembled nano-hydrogel according to claim 4, wherein the volume fraction of the piperidine solution in the step S4 and the step S6 is 20-40%, and the solvent of the piperidine solution is N, N-dimethylformamide.
  8. 8. The method for preparing quercetin-polypeptide co-assembled nano-hydrogel according to claim 4, wherein the cutting fluid comprises trifluoroacetic acid and triisopropylsilane in a volume ratio of water=95:2.5:2.5.
  9. 9. The use of a quercetin-polypeptide co-assembled nano-hydrogel according to claim 1 in the preparation of a medicament for ulcerative colitis.

Description

Quercetin-polypeptide co-assembled nano hydrogel and preparation method and application thereof Technical Field The invention relates to the technical field of biological medicine. More specifically, the invention relates to a quercetin-polypeptide co-assembled nano hydrogel, and a preparation method and application thereof. Background Ulcerative colitis (ulcerative colitis, UC) is one of the major forms of Inflammatory Bowel Disease (IBD) with an increasing incidence worldwide. The pathogenesis of ulcerative colitis is not thoroughly known, and besides typical intestinal manifestations such as abdominal pain, diarrhea, mucopurulent bloody stool and the like, the ulcerative colitis can also be accompanied by multiple organ and multiple system intestinal manifestations, which seriously affect the life and work of patients. For clinical treatment of ulcerative colitis, oral administration remains the most popular route because of its good patient compliance, safety, and direct administration to the colonitis tissue. However, conventional oral administration systems face multiple barriers in the gastrointestinal tract, such as acidic gastric juice, rich digestive enzymes, and viscous mucus layers, which make oral administration extremely challenging. Quercetin is a flavonoid compound widely distributed in flowers, leaves, fruits and seeds of plants and has multiple biological activities, and contains more than 100 medicinal plants such as cacumen Platycladi, herba Taxilli, rhizoma Alpiniae Officinarum, radix Notoginseng, flos Farfarae, etc. Quercetin has wide pharmacological effects including antioxidation and free radical removal, antivirus, anti-inflammatory, anti-tumor, blood sugar reduction, immunoregulation and the like, and can be used for treating ulcerative colitis, but the quercetin has poor water solubility, poor gastrointestinal stability, short in vivo half-life and low bioavailability, and limits the clinical application thereof. Therefore, there is an urgent need for a carrier or novel combination drug that can improve its water solubility, stability, and can be synergistically effective for treating ulcerative colitis. Disclosure of Invention It is an object of the present invention to solve at least the above problems and to provide at least the advantages to be described later. To achieve these objects and other advantages and in accordance with the purpose of the invention, there is provided a quercetin-polypeptide co-assembled nano-hydrogel comprising quercetin and a polypeptide in a mass ratio of 1:1-6, wherein the molecular formula of the polypeptide is R-G DFDFD Y, wherein R is a non-steroidal anti-inflammatory drug. Preferably, the preparation method of the quercetin-polypeptide co-assembled nano hydrogel comprises the following steps: adding phosphate buffer solution into the polypeptide, heating until the polypeptide is completely dissolved, adjusting the pH to 7-8, and standing at room temperature to form gel to obtain the polypeptide hydrogel. Adding phosphate buffer solution into the quercetin Pi Suzhong, heating until the quercetin is completely dissolved, and regulating the pH to 7-8 to obtain a quercetin Pi Sure solution; and thirdly, adding a quercetin Pi Sure solution into the polypeptide hydrogel, adding a phosphate buffer solution with pH of 7.4, heating to slight boiling, and standing at room temperature to form gel, thus obtaining the quercetin-polypeptide co-assembled nano hydrogel. Preferably, the polypeptide comprises a non-steroidal anti-inflammatory drug, a short peptide G DFDFD Y. Preferably, the method for preparing the polypeptide comprises the following steps: s1, dissolving N- (9-fluorenylmethoxycarbonyl) -O-tertiary butyl-D-tyrosine by using methylene dichloride, adding diisopropylethylamine, and mixing to obtain a reaction liquid I; S2, fully swelling the 2-Cl-Trt resin by adopting anhydrous dichloromethane, removing the dichloromethane, adding the reaction liquid I into a solid-phase synthesizer, reacting on a shaking table at room temperature, and obtaining a mixture 1 after the reaction is finished; s3, removing liquid in the mixture 1, washing for a plurality of times by adopting anhydrous dichloromethane, adding a sealing liquid, reacting on a shaking table at room temperature, and obtaining a mixture 2 after the reaction is finished, wherein the sealing liquid comprises dichloromethane, N diisopropylethylamine, methanol=17:1:2; S4, removing liquid in the mixture 2, sequentially adopting anhydrous dichloromethane and N, N-dimethylformamide to wash for a plurality of times, then adding a piperidine solution, reacting at room temperature, removing the liquid after the reaction is finished, and adopting N, N-dimethylformamide to wash for a plurality of times, wherein the solvent of the piperidine solution is N, N-dimethylformamide; S5, adding O-benzotriazole-tetramethyl urea Hexafluorophosphate (HBTU), diisopropylethylamine and N, N-dimethylformamide into N- (