CN-122005435-A - Oridonin-magnesium ion composite gel preparation for synergistic treatment of melanoma, preparation method thereof and application of oridonin-magnesium ion composite gel preparation in preparation of auxiliary treatment drug after melanoma operation

CN122005435ACN 122005435 ACN122005435 ACN 122005435ACN-122005435-A

Abstract

The invention relates to the technical field of biological medicines, in particular to an oridonin-magnesium ion composite gel preparation for synergistically treating melanoma, a preparation method thereof and application thereof in preparing auxiliary treatment medicines after melanoma operation. The preparation method comprises the steps of preparing carboxymethyl chitosan solution and sodium alginate solution, preparing oridonin loading component and magnesium loading component, regulating pH of a mixed system and fumigating and crosslinking glacial acetic acid at room temperature. According to the invention, uniform loading and continuous controllable release of the rubescensine A and magnesium ions are realized through a hydrogel three-dimensional network, the rubescensine A and the magnesium ions cooperatively induce melanoma A375 cells to generate active oxygen, inhibit cell proliferation and migration, and meanwhile, the anti-inflammatory and antibacterial activity of the rubescensine A and the wet healing property of the hydrogel can promote the repair of surgical wound surfaces.

Inventors

ZHAO LU
Liu Yunen
LIU CHUNYI
JIA YUJIE
YANG KE
Di Zexi
GONG YUHAN

Assignees

沈阳医学院

Dates

Publication Date: 20260512
Application Date: 20260206

Claims (8)

1. The oridonin-magnesium ion composite gel preparation for the synergistic treatment of melanoma is characterized by comprising synergistic active ingredients and a delivery carrier, wherein the synergistic active ingredients are oridonin and magnesium ions, the delivery carrier is carboxymethyl chitosan-sodium alginate composite hydrogel, the concentration of oridonin in the composite gel preparation is 10-200 mu M, and the content of magnesium is 100-750 mg/mL.
2. The oridonin-magnesium ion composite gel preparation for the synergistic treatment of melanoma according to claim 1, wherein in the composite gel preparation, magnesium ions are derived from medical grade magnesium powder, the particle size of the magnesium powder is 50-100 μm, and the purity is not less than 99.9wt%.
3. The oridonin-magnesium ion composite gel preparation for the synergistic treatment of melanoma according to claim 1, wherein in the composite gel preparation, the deacetylation degree of carboxymethyl chitosan is >90%, the concentration of carboxymethyl chitosan is 5-30 mg/mL, and the concentration of sodium alginate is 5-30 mg/mL.
4. A method of preparing an oridonin-magnesium ion composite gel formulation for the synergistic treatment of melanoma according to any one of claims 1 to 3, comprising the steps of: (1) Preparing carboxymethyl chitosan solution, namely dissolving 0.1-0.3 g of carboxymethyl chitosan with the deacetylation degree of more than 90% into 5mL of physiological saline, and oscillating and dissolving at room temperature to obtain uniform carboxymethyl chitosan solution; (2) Preparing sodium alginate solution, namely dissolving 0.1-0.3 g of sodium alginate in 5mL of physiological saline, and oscillating and dissolving at room temperature to obtain uniform sodium alginate solution; (3) The oridonin loading component is prepared by sucking 1mL of oridonin mother liquor, wherein the concentration of the oridonin mother liquor is 100 mu M-3 mM; (4) Preparing a magnesium load component, namely weighing 1.2 g-9 g of medical grade magnesium powder, and dispersing the medical grade magnesium powder in physiological saline; (5) Mixing and pH adjusting, namely mixing the carboxymethyl chitosan solution in the step (1), the sodium alginate solution in the step (2), the oridonin load component in the step (3) and the magnesium load component in the step (4), fully and uniformly stirring, and adjusting the pH value of the mixed liquid to 7-9; (6) And (3) gelation molding, namely placing the liquid uniformly mixed in the step (5) into a closed container, fumigating for 6-8 hours at room temperature in glacial acetic acid atmosphere, and enabling carboxymethyl chitosan and sodium alginate to be subjected to intermolecular crosslinking to form a three-dimensional network hydrogel structure, thereby obtaining the composite gel preparation.
5. The method for preparing oridonin-magnesium ion composite gel preparation for synergistic treatment of melanoma according to claim 4, wherein in step (5), hydrochloric acid or sodium hydroxide aqueous solution is used to adjust the pH value of the mixed liquid.
6. The method for preparing oridonin-magnesium ion composite gel preparation for synergistic treatment of melanoma according to claim 4, characterized in that in step (6), glacial acetic acid fumigation is carried out in a closed container, and volatile acid vapor of glacial acetic acid is used as a crosslinking initiator.
7. Use of an oridonin-magnesium ion composite gel formulation according to any one of claims 1 to 3 for the synergistic treatment of melanoma in the preparation of a medicament for the post-operative adjuvant treatment of melanoma.
8. The use according to claim 7, wherein the medicament is administered topically, and the composite gel formulation is applied directly to the surgical wound after melanoma excision, whereby a sustained and controlled release of the rabdosia rubescens element and magnesium ions is achieved by progressive degradation of the hydrogel.

Description

Oridonin-magnesium ion composite gel preparation for synergistic treatment of melanoma, preparation method thereof and application of oridonin-magnesium ion composite gel preparation in preparation of auxiliary treatment drug after melanoma operation Technical Field The invention relates to the technical field of biological medicines, in particular to an oridonin-magnesium ion composite gel preparation for synergistically treating melanoma, a preparation method thereof and application thereof in preparing auxiliary treatment medicines after melanoma operation, which are particularly suitable for local auxiliary treatment after melanoma excision and can synchronously realize operation wound repair and tumor recurrence prevention and control. Background Melanoma (Melanoma) is a highly malignant tumor that originates from melanocytes, and is the most aggressive and worst predicted among skin cancers. World health organization data statistics global morbidity is in a continuous rising trend, the estimated annual new cases for 2040 years will exceed 50 ten thousand, the estimated death number reaches about 9.6 ten thousand, and the serious threat to human health is [1]. At present, traditional therapies such as surgical excision, radiotherapy and chemotherapy remain the main means [2] for melanoma treatment. However, due to the presence of tumor cell residues or micrometastases, the postoperative recurrence rate remains high and patients often need adjuvant chemotherapy or immunotherapy to reduce the risk of recurrence. For example, when paclitaxel, temozolomide, carboplatin and the like are used as chemotherapeutic drugs for postoperative adjuvant therapy, intravenous infusion is usually carried out every 3 weeks for 6 months to 1 year, and the long-term and systemic administration mode is not only easy to cause systemic toxic and side effects such as bone marrow suppression, liver and kidney function injury and the like, but also has the advantages of insufficient local drug concentration and prominent drug resistance due to short half-life and poor targeting, and relapse or metastasis occurs in about half of patients in five years after operation, so that the overall curative effect is still not ideal, and the five-year survival time is only 17% [3]. Therefore, a novel postoperative treatment system capable of realizing local administration and slow release is developed, and the effective drug concentration in a focus area is maintained, and meanwhile, the systemic toxicity is reduced, so that the novel postoperative treatment system has urgent and important clinical significance for controlling melanoma recurrence and improving the prognosis of patients. Hydrogels are polymeric materials with three-dimensional network structures that have high water content and physical properties that make them highly similar in morphology and function to human soft tissues. Based on the unique porous structure, the hydrogel not only can efficiently absorb wound exudates and maintain a moist environment, but also can continuously play the positive roles of resisting bacteria and promoting healing by inhibiting bacterial colonization and relieving local inflammation. More importantly, the three-dimensional network can be used as an excellent drug carrier to realize the accurate loading and controllable release of various active components (such as antibiotics, growth factors and the like). The characteristic enables the hydrogel to organically combine the physical barrier function of the material with the therapeutic action of the exogenous medicine, thereby becoming a core material foundation for developing a novel wound care product with high-efficiency protection and active therapeutic functions. In recent years, researchers have focused on introducing a variety of functional components into hydrogel systems to construct smart dressings with synergistic therapeutic effects. For example, wang et al have developed a 5-fluorouracil (5-FU) loading system based on PEG-PCL-PEG (PECE) temperature-sensitive hydrogels for use in the treatment of colorectal cancer peritoneal metastases. The hydrogel is in an injectable sol state at room temperature, and forms a gel reservoir rapidly under the body temperature condition after being injected into the abdominal cavity, so that the local slow release of the medicine is realized. Animal experiment results show that the 5-FU-hydrogel system remarkably inhibits the spreading and growth of CT26 cancer cells on the peritoneum of mice, reduces the average tumor node number to 5.3+/-4.04, and realizes the tumor-free survival rate of 42.5%. Meanwhile, the system effectively reduces the hematological toxicity caused by 5-FU, which shows that the reduction of the white blood cell number is small in amplitude and the whole biosafety is good. Kim constructs a thermosensitive hydrogel based on gelatin and Pluronic F127, and is used for jointly loading BRAF inhibitor vitamin Mo Feini (Vem) and anti-