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Crosslinked hemostatic sponge with hemostatic and postoperative anti-tumor functions and preparation method thereof

A hemostatic sponge and anti-tumor technology, applied in the field of cross-linked hemostatic sponge and its preparation, can solve the problems of difficult to effectively control tumor metastasis, recurrence, killing, etc., and achieve the effects of excellent hemostatic performance, promotion of blood coagulation, and good hemostatic function.

Active Publication Date: 2021-06-11
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The purpose of the present invention is to overcome the deficiencies of the prior art, to provide a cross-linked hemostatic sponge with both hemostatic and postoperative anti-tumor functions and its preparation method, so as to solve the problem that the existing drug delivery system is difficult to effectively control the tumor caused by intraoperative bleeding Insufficient metastasis and recurrence problems, through the hemostatic adsorption of the hemostatic sponge, reduce bleeding and reduce the number of circulating tumor cells, and co-deliver nanoparticles to residual tumor cells and scattered tumor cells through the co-delivery of cross-linked drugs in the hemostatic sponge Antitumor drugs, persistently kill cancer cells, effectively inhibit postoperative tumor recurrence and metastasis

Method used

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  • Crosslinked hemostatic sponge with hemostatic and postoperative anti-tumor functions and preparation method thereof
  • Crosslinked hemostatic sponge with hemostatic and postoperative anti-tumor functions and preparation method thereof
  • Crosslinked hemostatic sponge with hemostatic and postoperative anti-tumor functions and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] In this example, controlled-release drug-loaded nanoparticles were prepared, specifically, amphiphilic prodrug polymer double-drug nanomicelles with natural polymer pullulan as the carrier. Proceed as follows:

[0051] (1) Preparation of carboxymethylated pullulan

[0052] Weigh 5.0g of pullulan and dissolve it in 20mL of deionized water, then slowly add 6mL of isopropanol dropwise into the pullulan aqueous solution, and dissolve the prepared sodium hydroxide aqueous solution (sodium hydroxide 1.3g in 3mL to deionized water) was added dropwise to the pullulan solution, and reacted at 70°C for 15 minutes; after the reaction was completed, it was cooled to room temperature, and an aqueous solution of sodium chloroacetate (2.5 g of sodium chloroacetate was dissolved in 3 mL of deionized water) and 3 mL of isopropanol were dropped Add it to the reaction solution and react at 70°C for 1h; repeat the operation of adding sodium hydroxide aqueous solution, sodium chloroacetate...

Embodiment 2

[0060] In this example, cysteine ​​hydrochloride is used to modify hyaluronic acid (HA) with thiol to prepare thiol-modified hyaluronic acid (HA-SH), the steps are as follows:

[0061] Take 400 mg of sodium hyaluronate with a molecular weight of 0.1 MDa and dissolve it in 50 mL of deionized water. After the dissolution is complete, add 232 mg of N-hydroxysuccinimide (NHS) and 965 mg of 1-ethyl-(3-dimethylaminopropyl base) carbodiimide hydrochloride (EDC·HCl), after stirring at room temperature for 2 hours, add cysteamine hydrochloride aqueous solution (obtained by dissolving 571mg cysteine ​​hydrochloride (CSH·HCl) in deionized water ), stirred at room temperature for 12 hours, and maintained the pH of the reaction system at 4.75-5.0 by adding 1 mol / L NaOH or 1 mol / L HCl dropwise during the entire reaction. After the reaction, the resulting reaction solution was transferred into a dialysis bag, purified by dialysis in deionized water with pH = 3.0, and freeze-dried to obtain w...

Embodiment 3

[0066] In this example, PP-Dox / Lap nanoparticles and HA-SH were used to prepare a cross-linked hemostatic sponge (HCNPs sponge) with both hemostatic and postoperative anti-tumor functions. The steps are as follows:

[0067] (1) Weigh 40 mg of HA-SH prepared in Example 2 and dissolve it in PBS buffer, adjust the pH value to 7.0 with 1mol / L NaOH solution, then add the PP-Dox / Lap nanoparticles (PP -The addition of Dox / Lap nanoparticles should ensure that the prepared cross-linked hemostatic sponge contains Dox 0.1mg, Lap 1.1mg), mix well to obtain reaction solution A; in reaction solution A, the concentration of HA-SH is 2wt% .

[0068] (2) Weigh 40 mg type I collagen (COL I) and dissolve it in 0.5 mol / L acetic acid, adjust the pH value to 7.0 with 1 mol / L NaOH solution to obtain reaction solution B; in reaction solution B, the concentration of COL I is 2 wt%. .

[0069] (3) Fully mix the reaction solution A and the reaction solution B, and let it stand at 37°C for 2 hours to o...

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Abstract

The invention provides a crosslinked hemostatic sponge with hemostatic and postoperative anti-tumor functions. The cross-linked hemostatic sponge is composed of a composite three-dimensional network structure formed by cross-linked modified hyaluronic acid and collagen substances and controlled-release drug-loaded nanoparticles distributed in the composite three-dimensional network structure, and the cross-linked hemostatic sponge has a porous structure. The cross-linked modified hyaluronic acid is formed by self-crosslinking of modified hyaluronic acid, the controlled-release drug-loaded nanoparticles are combined with the cross-linked modified hyaluronic acid through chemical bonds, and the drug loaded by the controlled-release drug-loaded nanoparticles is an anti-tumor drug. The cross-linked hemostatic sponge provided by the invention not only can reduce bleeding and reduce the number of circulating tumor cells, but also can slowly release and release anti-tumor drugs into residual tumor cells and scattered tumor cells through the cross-linked and loaded drug co-delivery nanoparticles, continuously kills cancer cells, and effectively inhibits recurrence and metastasis of postoperative tumors.

Description

technical field [0001] The invention belongs to the field of medical biomaterials, and relates to a cross-linked hemostatic sponge with both hemostatic and postoperative antitumor functions and a preparation method thereof. Background technique [0002] Surgical resection is the main method for the treatment of early-stage cancers. However, the long-term prognosis after tumor resection is poor, and the high incidence of tumor recurrence and metastasis often leads to high mortality of postoperative patients. Therefore, effective prevention of postoperative tumor recurrence and metastasis is one of the key means to improve the prognosis and long-term survival rate of patients. In recent years, researchers have conducted extensive research on the possible mechanisms of postoperative tumor recurrence and metastasis, and proposed that the small lesions remaining at the margin of surgical resection are the main reason for tumor recurrence; at the same time, during the process of t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61L24/08A61L24/10A61L24/00
CPCA61L24/0036A61L24/0094A61L24/0015A61L2300/626A61L2300/416A61L2400/04A61L2300/418A61L2300/252A61L2300/602C08L89/00C08L5/08
Inventor 孙勇赵明达樊渝江随俊慧张兴栋
Owner SICHUAN UNIV
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