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CN-122005610-A - Carbon quantum dot based on taurine and glucose and application thereof in preparing synergistic hypoglycemic drugs

CN122005610ACN 122005610 ACN122005610 ACN 122005610ACN-122005610-A

Abstract

The invention relates to a taurine and glucose based carbon quantum dot and application thereof in preparing a synergistic hypoglycemic drug. The carbon quantum dot is prepared from glucose and taurine according to a molar ratio of 1:10-10:10 by a hydrothermal method, has a particle size of 2-10 nm and has a graphitized lattice structure. The carbon quantum dot has high-efficiency scavenging capability on hydroxyl radicals and nitrogen radicals. The zebra fish model experiment proves that the carbon quantum dots inhibit the gluconeogenesis process by inhibiting the expression of glucagon genes, obviously reduce the apoptosis of pancreatic cells induced by high sugar, lighten the oxidative stress level and realize high-efficiency sugar reduction through the cooperation of multiple mechanisms. Compared with taurine monomer, the carbon quantum dot obviously reduces the cardiotoxicity under the same concentration, and solves the safety problem of high-dose use of taurine. The preparation method provided by the invention is simple and low in cost, and the obtained carbon quantum dot has the characteristics of high efficiency in reducing blood sugar and high safety, and can be used for preparing the medicine for treating type 2 diabetes.

Inventors

  • LI LI
  • CONG JIA
  • CHEN CE
  • Jiang Panshan
  • WANG SIHAN
  • LI BINGSHENG

Assignees

  • 哈尔滨工业大学

Dates

Publication Date
20260512
Application Date
20260317

Claims (10)

  1. 1. The carbon quantum dot based on taurine and glucose is characterized in that the carbon quantum dot is prepared from glucose and taurine serving as precursors, wherein the molar ratio of glucose to taurine is 1:10 to 10:10.
  2. 2. The taurine and glucose based carbon quantum dot of claim 1, wherein the carbon quantum dot has a particle size of 2-10 nm, a graphitized lattice structure, and a lattice spacing of 0.20-0.24 nm.
  3. 3. A method for preparing the taurine and glucose based carbon quantum dots of claim 1 or 2, characterized by comprising the steps of: Step 1, glucose and taurine are dissolved in deionized water according to a molar ratio of 1:10 to 10:10, and are stirred until the glucose and the taurine are completely dissolved, so that a precursor solution is obtained; Step, placing the precursor solution obtained in the step 1 into a reaction kettle for hydrothermal reaction, wherein the reaction temperature is 140-220 ℃ and the reaction time is 4-24 h, so as to obtain a brown-black reaction solution; step 3, centrifuging the brown-black reaction liquid obtained in the step 2, and taking supernatant; step 4, dialyzing the supernatant obtained in the step 3 to remove unreacted micromolecular substances; And 5, freeze-drying the solution dialyzed in the step 4 to obtain brown-black solid powder, namely the carbon quantum dots based on taurine and glucose.
  4. 4. The preparation method according to claim 3, wherein the hydrothermal reaction in step 2 has a reaction temperature of 160-200 ℃ and a reaction time of 8-16 h, the centrifugation in step 3 has a rotational speed of 10000-15000 rpm and a centrifugation time of 15-30 min, and the dialysis bag used in the dialysis in step 4 has a molecular weight cut-off of 500-2000 Da and a dialysis time of 24-72 h.
  5. 5. The use of the taurine and glucose based carbon quantum dots of claim 1 or 2 in the preparation of a synergistic hypoglycemic drug; The synergistic hypoglycemic medicine cooperatively plays a hypoglycemic role through the following various mechanisms: Inhibit the expression of the glucagon gene, further inhibit gluconeogenesis process; Inhibit pancreatic apoptosis; Scavenging hydroxyl radicals and nitrogen radicals, and reducing oxidative stress level.
  6. 6. The application of the carbon quantum dot as set forth in claim 5, wherein the concentration of the carbon quantum dot for scavenging hydroxyl radicals and nitrogen radicals is 0.1-2.0 mg/mL, the scavenging rate of the hydroxyl radicals is 10% -30%, and the scavenging rate of the nitrogen radicals is 20% -98%.
  7. 7. The application of the carbon quantum dot according to claim 5, wherein the concentration of the carbon quantum dot acting on the type 2 diabetes model is 62.5-1000 mug/mL, and the acting time is 6-12h.
  8. 8. The method of claim 5, wherein the carbon quantum dots have lower cardiotoxicity at the same concentration as compared with taurine monomers, and the adverse effect of heart rate abnormality caused by high dosage of taurine monomers can be avoided.
  9. 9. A pharmaceutical composition comprising the taurine-and glucose-based carbon quantum dot of claim 1 or 2, and a pharmaceutically acceptable carrier or adjuvant.
  10. 10. The pharmaceutical composition according to claim 9, wherein the pharmaceutical composition is an oral preparation or an injection for treating type 2 diabetes.

Description

Carbon quantum dot based on taurine and glucose and application thereof in preparing synergistic hypoglycemic drugs Technical Field The invention relates to the technical field of biological medicines and nano materials, in particular to a carbon quantum dot based on taurine and glucose, a preparation method thereof and application of the carbon quantum dot in preparing a synergistic hypoglycemic medicine. Background Type 2 diabetes (Type 2 Diabetes Mellitus,T2DM) is a metabolic disease characterized by insulin resistance and progressive islet beta cell failure, the core pathology of which is manifested as persistent hyperglycemia. Based on published data of the international diabetes consortium (IDF) 2021, the number of adult-onset diabetes patients of 20-79 years old worldwide has reached 5.37 million, with type 2 diabetes accounting for about 90% or more, and it is expected that 2045 years will increase to 7.83 million. Diabetes is one of the main causes of blindness, renal failure, myocardial infarction, cerebral apoplexy and lower limb amputation, and brings about a heavy economic and social burden to the global healthcare system. The blood glucose lowering drugs commonly used in clinic at present mainly comprise biguanides (such as metformin), sulfonylureas, thiazolidinediones, alpha-glycosidase inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, SGLT-2 inhibitors, insulin preparations and the like. Although these drugs are capable of controlling blood sugar to a certain extent, long-term use often accompanies various side effects, such as the risk of gastrointestinal discomfort and lactic acidosis caused by metformin, the tendency of sulfonylureas to cause hypoglycemia and weight gain, the high price of GLP-1 receptor agonists and DPP-4 inhibitors, and the potential risk of pancreatitis, insulin formulations requiring injection administration and severe transportation and storage conditions (requiring 2-8 ℃ refrigeration), and limited use in underdeveloped areas and resource-deficient areas. Therefore, the development of hypoglycemic drugs with high safety, low cost and novel action mechanism is still an important direction in the current diabetes research field. Taurine (Taurine), known as 2-aminoethanesulfonic acid, is a sulfur-containing non-protein amino acid that is widely found in mammalian tissues, particularly heart, retina and skeletal muscle. Taurine participates in various physiological processes such as bile acid binding, osmotic pressure regulation, membrane stabilization, calcium ion regulation and the like in vivo. In recent years, taurine has been found to play an important role in regulating the metabolism of glycolipid, and taurine can improve the disorder of glycometabolism through various ways such as activating an insulin signal pathway, improving insulin sensitivity, reducing the level of oxidative stress, inhibiting inflammatory reaction, regulating the secretion of glucagon-like peptide-1 (GLP-1) and the like. Animal experiments and clinical researches show that taurine supplementation can reduce the blood sugar level of diabetic model animals and diabetics and delay the progress of diabetic complications. Taurine, however, also presents some challenges in clinical applications. High dose ingestion of taurine may cause adverse reactions including cardiovascular side effects such as tachycardia, arrhythmia, blood pressure fluctuations, and gastrointestinal discomfort. These dose-related safety issues have limited to a certain extent the wide use of taurine in the treatment of diabetes. How to reduce the toxic and side effects of taurine while retaining the hypoglycemic activity is a concern of researchers. The carbon quantum dots (Carbon Quantum Dots, CQDs) are novel zero-dimensional carbon-based nano materials with the size smaller than 10 nm, and have the advantages of good water solubility, biocompatibility, low toxicity, optical stability, easiness in surface functionalization and the like. The carbon quantum dots can be synthesized by a 'bottom-up' method (such as a hydrothermal method and a microwave method) by taking small molecular organic matters as precursors, and the preparation process is simple and controllable. Research shows that the carbon quantum dot can be used as a biological imaging probe and has various biological activities such as antioxidation, antibiosis, anti-inflammatory and the like. More importantly, the preparation of the bioactive molecules into the carbon quantum dots can often keep the biological functions of the original molecules and improve the pharmacokinetic properties and the safety of the original molecules. For example, carbon quantum dots prepared by using amino acids, polysaccharides and natural products as precursors show stronger antioxidant capacity and lower cytotoxicity while retaining the activity of the original molecules. Glucose is used as a main energy source of organisms and is also one of carbon sources commonly used in