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Preparation method and application of gel for in-situ delivery of nano-micelles

A nanomicelle and gel technology, applied in the field of biomedical materials, can solve the problem of limited accumulation of nanomicelles, and achieve the effects of improving bioavailability, avoiding systemic toxicity, and enhancing chemotherapy efficiency

Active Publication Date: 2022-05-24
济南国科医工科技发展有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, although the properties of nanomicelles such as size, shape, surface characteristics, and payload have been well studied, the accumulation of nanomicelles delivered via veins in the tumor part is still very limited, and most of the nanomicelles are found in other organs. accumulate or clear

Method used

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  • Preparation method and application of gel for in-situ delivery of nano-micelles
  • Preparation method and application of gel for in-situ delivery of nano-micelles
  • Preparation method and application of gel for in-situ delivery of nano-micelles

Examples

Experimental program
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Embodiment 1

[0039] Example 1, the synthesis and characterization of the polymer poly(5-ethylene glycol ketal-ε-caprolactone-ε-caprolactone)-polyethylene glycol monomethyl ether.

[0040] Weigh 5.0 g of polyethylene glycol monomethyl ether (molecular weight: 2000 Da) into a 25 mL dry glass reactor, dry in vacuum at 60°C for 1 hour, add 2.74 g of monomer 5-ethylene glycol under nitrogen protection Ketal-ε-caprolactone and 7.26g of ε-caprolactone, then add 0.1mL stannous octoate, degas and seal under reduced pressure. After stirring at 130°C for 6 hours, it was dissolved in dichloromethane, and then added dropwise to an excess of cold ether for precipitation. After the precipitate was filtered, it was vacuum-dried at room temperature to obtain the polymer poly(5-ethylene glycol ketal) -ε-caprolactone-ε-caprolactone)-polyethylene glycol monomethyl ether.

[0041] synthetic polymer 1 The H NMR spectrum is attached figure 1 As shown, the structure of the polymer and the corresponding NMR pea...

Embodiment 2

[0042] Example 2, the synthesis and characterization of the polymer poly(5-ethylene glycol ketal-ε-caprolactone-ε-caprolactone)-polyethylene glycol monomethyl ether with paclitaxel molecules bonded by disulfide bonds.

[0043] Weigh 1.0 g of poly(5-ethylene glycol ketal-ε-caprolactone-ε-caprolactone)-polyethylene glycol monomethyl ether synthesized in Example 1, and dissolve it in 10 mL of dichloromethane , add dropwise a dichloromethane solution (5 mL) of 0.05 g of triphosgene in an ice-water bath, and after incubation for 30 minutes, add a solution of 0.052 g of 2-hydroxyethyl disulfide in dichloromethane (5 mL) . After reacting at room temperature for 24 hours, it was added dropwise into pre-cooled diethyl ether to precipitate, and the product was obtained after filtration. Further, the product was dissolved in 10 mL of tetrahydrofuran, dialyzed in water with a dialysis bag with a molecular weight cut-off of 3.5 KDa, and the product was freeze-dried after dialysis.

[004...

Embodiment 3

[0045] Example 3, synthesis and characterization of modified RGD cyclic peptide-polyethylene glycol-poly(5-ethylene glycol ketal-ε-caprolactone-ε-caprolactone).

[0046] The polyethylene glycol monomethyl ether in embodiment 1 is replaced by succinimide ester-polyethylene glycol (molecular weight is 2000kDa), all the other steps are identical with embodiment, synthetic succinimide ester-polyethylene glycol- Poly(5-ethylene glycol ketal-ε-caprolactone-ε-caprolactone); take 0.1 of the above polymer, dissolve it in 5 mL of PBS, add 0.015 g of cyclic RGD polypeptide, and incubate for another 24 hours. Then the target product was obtained after purification by dialysis.

[0047] The combination of the prepared products and 1 The H NMR spectrum is attached image 3 shown. The NMR peaks representing the cyclic RGD were observed, proving that the cyclic RGD was successfully indirect on the polymer chain segment.

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Abstract

The invention discloses a preparation method of a gel system. Comprising the following steps: synthesis of poly (5-ethylene ketal-epsilon-caprolactone-epsilon-caprolactone)-polyethylene glycol monomethyl ether, synthesis of poly (5-ethylene ketal-epsilon-caprolactone-epsilon-caprolactone)-polyethylene glycol monomethyl ether bonded with paclitaxel molecules, synthesis of RGD cyclopeptide-polyethylene glycol-poly (5-ethylene ketal-epsilon-caprolactone-epsilon-caprolactone), synthesis of poly (5-ethylene ketal-epsilon-caprolactone), synthesis of poly (5-ethylene ketal-epsilon-caprolactone), synthesis of poly (5-ethylene ketal-epsilon-caprolactone) and synthesis of poly (5-ethylene ketal-epsilon-caprolactone). The preparation method comprises the following steps: preparing a paclitaxel drug, preparing a nano-micelle, synthesizing and the like, the gel prepared on the basis of the method has injectability and can release the functional nano-micelle in situ, and the released nano-micelle can specifically target tumor cells, can respond to glutathione in the tumor cells to release the paclitaxel drug and promote death of the tumor cells.

Description

technical field [0001] The invention relates to biomedical materials, in particular to a preparation method and application of a gel for in-situ delivery of nanomicelles. Background technique [0002] Cancer is a major public health problem that threatens human life and health. Chemotherapy remains the mainstay of treatment for many types of cancer. However, traditional anti-tumor chemotherapy methods generally use intravenous administration. Due to the lack of selectivity in the way of administration and drugs, traditional chemotherapy has the problems of low treatment efficiency and serious systemic adverse reactions. Therefore, increasing the accumulation of drugs in tumor sites and improving the bioavailability of drugs is of great significance for improving the efficiency of chemotherapy and reducing side effects. [0003] Topical administration is a method of administering drugs in or around the tumor. Compared with intravenous administration, the local drug deliver...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/06A61K47/60A61K47/64A61K47/69A61K31/337A61P35/00
CPCA61K9/06A61K9/0019A61K47/60A61K47/64A61K47/6907A61K47/6951A61K31/337A61P35/00
Inventor 许舒欣李小强
Owner 济南国科医工科技发展有限公司
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