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CN-120501841-B - Exosome composition for reducing side effects of chemotherapy treatment and preparation method thereof

CN120501841BCN 120501841 BCN120501841 BCN 120501841BCN-120501841-B

Abstract

The invention provides an exosome composition for reducing side effects of chemotherapy and a preparation method thereof, belonging to the technical field of medicines. The method comprises the steps of preparing methotrexate, vinblastine and daunorubicin into eutectic crystals, loading the eutectic crystals on UiO-66-NH 2 connected with RGD, loading the eutectic crystals on exosomes, embedding the eutectic crystals in an acrylic acid, traditional Chinese medicine polysaccharide and pullulan polysaccharide compound to prepare a slow-release high half-life exosome system, uniformly mixing the slow-release high half-life exosome system with D-ribose, yeast-beta glucan and glutathione to prepare the exosome composition for reducing side effects of chemotherapy treatment, wherein the traditional Chinese medicine polysaccharide is obtained by extracting dangshen, angelica, rhizoma polygonati and dendrobium officinale with boiling water and precipitating with ethanol. The exosome composition for reducing the side effects of chemotherapy is prepared, reduces the drug resistance of tumor cells, improves the drug effect, reduces the side effects after chemotherapy, realizes the effect of targeted slow release of drugs, and has wide application prospect.

Inventors

  • WANG BAOYU
  • TIAN JIANXIAO
  • GONG YUQIN

Assignees

  • 广州爱索达生物医药技术有限公司

Dates

Publication Date
20260508
Application Date
20250521

Claims (8)

  1. 1. The preparation method of the exosome composition for reducing the side effects of the chemotherapy of the gastric cancer is characterized by preparing methotrexate, vinblastine and daunorubicin into eutectic crystals, loading the eutectic crystals on UiO-66-NH 2 connected with RGD, loading the eutectic crystals on exosomes, embedding the eutectic crystals in an acrylic acid, traditional Chinese medicine polysaccharide and pullulan polysaccharide compound to prepare a slow-release exosome system with high half-life, uniformly mixing the slow-release exosome system with D-ribose, yeast-beta glucan and glutathione to prepare the exosome composition for reducing the side effects of the chemotherapy of the gastric cancer, wherein the traditional Chinese medicine polysaccharide is obtained by extracting dangshen, angelica, rhizoma polygonati and dendrobium candidum with boiling water and precipitating with ethanol; The method comprises the following steps: S1, dissolving methotrexate in an alkali solution to prepare a solution 1, dissolving vinblastine in ethanol to prepare a solution 2, dissolving daunorubicin in water to prepare a solution 3, uniformly mixing the solution 1, the solution 2 and the solution 3, volatilizing through an opening, filtering, washing, drying and grinding to prepare chemical eutectic powder, wherein the concentration of the alkali solution is 5-10wt%, the alkali is NaOH or KOH, and the mass ratio of the methotrexate, the vinblastine and the daunorubicin is 3-5:1-3:3-6; S2, adding arginine-glycine-aspartic acid RGD into water, adding NHS and EDC, stirring for activation, adding UiO-66-NH 2 , stirring for reaction, centrifuging, washing and drying to obtain a UiO-66-NH 2 /RGD compound, wherein the mass ratio of the arginine-glycine-aspartic acid RGD, NHS, EDC to the UiO-66-NH 2 is 2-4:0.5-1:0.5-1:7-10; S3, adding the UiO-66-NH 2 /RGD compound into water, adding NHS and EDC, stirring for activation, adding chemical eutectic powder, stirring for reaction, centrifuging, washing and drying to obtain a medicine carrying body, wherein the mass ratio of the UiO-66-NH 2 /RGD compound to the NHS to the EDC to the chemical eutectic powder is 10-15:2-3:2-3:3-6; s4, adding the exosome into water, adding a medicine carrying body, carrying out ultrasonic incubation, centrifuging, washing and drying to obtain a medicine carrying system of the exosome, wherein the exosome is a mesenchymal stem cell exosome, and the mass ratio of the exosome to the medicine carrying body is 10-12:4-7; S5, cleaning, drying and crushing codonopsis pilosula, chinese angelica, rhizoma polygonati and dendrobium candidum, adding the mixture into water, heating, boiling and extracting, filtering, reserving filter residues, adding ethanol into the filtrate for precipitation, filtering, washing solids, and drying to obtain traditional Chinese medicine polysaccharide, wherein the mass ratio of the codonopsis pilosula to the Chinese angelica to the rhizoma polygonati to the dendrobium candidum is 5-10:5-10:3-7:10-15; S6, adding acrylic acid, traditional Chinese medicine polysaccharide and pullulan into water, adding an exosome drug-carrying system, then adding an initiator, an emulsifier and N, N' -methylene bisacrylamide, stirring and mixing uniformly, adding the mixture into fish oil, emulsifying, crosslinking, centrifuging, washing and drying to obtain a slow-release exosome system with high half-life; S7, uniformly mixing the D-ribose, the yeast-beta glucan, the glutathione and the slow-release high half-life exosome system to prepare the exosome composition for reducing the side effect of the chemotherapy of the gastric cancer.
  2. 2. The method according to claim 1, wherein the time for volatilizing the opening in step S1 is 7-10d.
  3. 3. The method according to claim 1, wherein the stirring and activating time in the step S2 is 20-40min, and the stirring and reacting time is 12-15h.
  4. 4. The method according to claim 1, wherein the stirring and activating time in the step S3 is 20-40min, and the stirring and reacting time is 10-14h.
  5. 5. The method according to claim 1, wherein the power of the ultrasonic incubation in step S4 is 300-500W, the temperature is 36-38 ℃ and the time is 10-12h.
  6. 6. The method according to claim 1, wherein the heating boiling extraction time in step S5 is 3 to 5 hours.
  7. 7. The preparation method of claim 1, wherein in the step S6, the mass ratio of the acrylic acid, the traditional Chinese medicine polysaccharide, the pullulan polysaccharide, the exosome drug-carrying system, the initiator, the emulsifier and the N, N' -methylenebisacrylamide is 3-7:5-10:3-5:6-8:0.05-0.1:0.5-1:0.4-0.8, the initiator is at least one selected from potassium persulfate, ammonium persulfate and sodium persulfate, the emulsifier is at least one selected from span-20, span-40, span-60, span-80, tween-20, tween-40, tween-60 and tween-80, the temperature of the crosslinking reaction is 50-60 ℃ and the time is 3-5h, and the mass ratio of the D-ribose, the yeast-beta glucan, the glutathione and the slow release high half-life exosome system in the step S7 is 1-3:4-8:2-4:15-20.
  8. 8. An exosome composition for reducing side effects of chemotherapy for gastric cancer prepared by the preparation method of any one of claims 1 to 7.

Description

Exosome composition for reducing side effects of chemotherapy treatment and preparation method thereof Technical Field The invention relates to the technical field of medicines, in particular to an exosome composition for reducing side effects of chemotherapy and a preparation method thereof. Background Tumors are organisms which are formed by abnormal proliferation of variant cells due to the fact that the human body loses the capability of regulating and controlling local variant cells under pathogenic factors. So once the tumor is formed, the tumor can rapidly grow without crazy controlled by human body and infringe to destroy normal tissues and organs of human body, and can be transferred to the whole body of the patient when serious, thereby leading to death of the patient. Chemotherapy was first used for symptomatic relief of acute lymphoblastic leukemia in the 40 s of the 19 th century, and then with continued intensive research of chemotherapy techniques, it was clinically found that chemotherapy can also relieve the disease against solid tumors for a long time, and then clinical therapeutic value of adjuvant chemotherapy techniques after cancer surgery was found. Through the exploration and development of over a century, new chemotherapeutics are continuously developed until the 80-90 s of the 20 th century, thereby further enriching and facilitating the formulation and selection of chemotherapeutics by doctors and obviously improving the clinical effect of chemotherapeutics. The preoperative chemotherapy of cancer has great clinical benefit in the treatment of various tumors, and especially the combined treatment can effectively relieve the illness state and prolong the life of patients for various tumors. Compared with other treatment means, the radiotherapy and chemotherapy still belong to tumor treatment schemes with large application range, long action time and more definite curative effect at the present stage. The medicine community is continuously researching and creating new chemotherapeutics so far, so as to further improve the chemotherapeutics effect and simultaneously reduce side effects caused by chemotherapy, and improve the tolerance and compliance of patients. Meanwhile, the combined application of chemotherapeutic drugs and molecular targeted drugs, and new therapeutic means for personalized and accurate drug administration are also opening new directions of cancer chemotherapy. Disclosure of Invention The invention aims to provide an exosome composition for reducing side effects of chemotherapy and a preparation method thereof, which improves the water solubility of a chemotherapeutic drug, reduces the use amount of the chemotherapeutic drug, reduces the drug resistance of tumor cells, synergistically improves the drug effect, reduces the side effects after the chemotherapy, improves the drug loading capacity by adopting a UiO-66-NH 2/RGD complex, can better complex the exosome, realizes the effect of targeted drug release, reduces the side effects of the drug, is embedded in an acidified polysaccharide shell layer, has better acid resistance, prolongs the half-life of the exosome, can protect the exosome from enzymolysis and immune attack, can realize slow release, and has wide application prospect. The technical scheme of the invention is realized as follows: The invention provides a preparation method of an exosome composition for reducing side effects of chemotherapy, which is prepared from the following raw materials of radix codonopsitis, angelica sinensis, rhizoma polygonati, dendrobium candidum, D-ribose, yeast-beta glucan and glutathione. As a further improvement of the invention, methotrexate, vinblastine and daunorubicin are prepared into eutectic crystals, loaded on UiO-66-NH 2 which is connected with RGD, loaded on exosomes, and embedded in an acrylic acid, traditional Chinese medicine polysaccharide and pullulan polysaccharide compound to prepare a slow-release high half-life exosome system, and the slow-release high half-life exosome system is uniformly mixed with D-ribose, yeast-beta glucan and glutathione to prepare the exosome composition for reducing the side effect of chemotherapy treatment, and the traditional Chinese medicine polysaccharide is obtained by extracting dangshen, angelica, rhizoma polygonati and dendrobium candidum with boiling water and precipitating with ethanol. As a further improvement of the invention, the method comprises the following steps: S1, dissolving methotrexate in an alkali solution to prepare a solution 1, dissolving vinblastine in ethanol to prepare a solution 2, dissolving daunorubicin in water to prepare a solution 3, uniformly mixing the solution 1, the solution 2 and the solution 3, volatilizing through an opening, filtering, washing, drying and grinding to prepare chemical eutectic powder; S2, adding arginine-glycine-aspartic acid RGD into water, adding NHS and EDC, stirring for activation, adding UiO-66-NH 2, stirring for