Nano-gel, preparation method thereof and anti-tumor drug-loading nano-gel

A nanogel and reaction technology, which is applied in the direction of antineoplastic drugs, drug combinations, and pharmaceutical formulations, can solve the problems of poor biocompatibility, poor water solubility and stability, and large toxic and side effects of drugs, and achieve good biocompatibility , good water solubility and stability, and the effect of improving the anti-tumor effect

Active Publication Date: 2019-07-05
CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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  • Abstract
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AI Technical Summary

Benefits of technology

This patented inventive formulation describes a new type of material called Nanoparticles or Microspheres made up of small molecules like proteins attached through linkers between them. These materials have unique properties such as being able to carry medicine into cancerous tissues for better treatment while reducing their harmful side effects on healthy ones. They may even help deliver these medications deeper within blood vessels without losing their efficacy due to poor circulation caused by lymphatic system constriction. Overall, this innovative technology allows scientists to creatively design effective treatments against various types of diseases including brain glioma.

Problems solved by technology

This patented technical problem addressed in this patents relates to improving the performance of anti-tumoral agents (chemo) when administered alone without causing harmful side effects such as inflammations, bleeding from blood vessels, nausea, fatigue, pain, fever, swelling, etc., which may lead to life-threatened conditions like leukemia and lung disease. Current treatments involve either chemotheraphy or radioactive techniques but they also cause severe damages to surrounding organs including heart muscle, kidneys, lungs, skin, eyes, brain, bones, livers, gastrointestinal tract, stomach, pancrease, abdominoyma, urinary bladder, uteroscopy, hysteroscopes, breast implants, cardiovascular procedures, radiosurgerancies, pulmonary embolisms, cranial necrosis, spine fusions, orthopedic surgeries, dental operations, and even invasiveness issues associated therewith.

Method used

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preparation example Construction

[0087] The present invention also provides a method for preparing the nanogel described in the above technical solution, characterized in that, comprising the following steps:

[0088] a) Under the action of an initiator, react aminated allyl polyethylene glycol with 2-(Boc-amino)ethanethiol in the first organic solvent to form tert-butoxycarbonyl-polyethylene glycol-amino compound;

[0089] b) reacting the tert-butoxycarbonyl-polyethylene glycol-amino compound with L-cystine-N-cyclic anhydride and L-phenylalanine-N-cyclic anhydride in a second organic solvent, Formation of tert-butoxycarbonyl-imino-polyethylene glycol-poly(L-phenylalanine-co-L-cystine);

[0090] c) Under acidic conditions, the tert-butoxycarbonyl-imino-polyethylene glycol-poly(L-phenylalanine-co-L-cystine) is removed in a third organic solvent The reaction of tert-butoxycarbonyl forms the compound of formula (VII);

[0091]

[0092] d) dissolving the compound of formula (VII) in a fourth organic solvent...

Embodiment 1

[0191] Embodiment 1: Preparation of tert-butoxycarbonyl-polyethylene glycol-amino

[0192] Put 1g of aminated allyl polyethylene glycol in a dry reaction flask, add 10mL of N'N-dimethylformamide, then add 0.3g of 2-(Boc-amino)ethanethiol and 2.3g of azobis isobutyronitrile, stirred and reacted under nitrogen atmosphere for 3 days to obtain a reaction solution. The resulting reaction solution was poured into 100 mL of anhydrous diethyl ether, the solid was obtained by suction filtration, and dried in vacuum to obtain tert-butoxycarbonyl-polyethylene glycol-amino, which is the compound represented by formula (VI).

[0193]

[0194] Wherein, m is the degree of polymerization, 40≤m≤120.

Embodiment 2

[0195] Embodiment 2: the preparation of L-phenylalanine-N-anhydride in the ring

[0196] Mix 1g of L-phenylalanine and 0.6g of bis(trichloromethyl)carbonate at 25°C, add 50mL of tetrahydrofuran, heat to 50°C for 2 hours, after the reaction, settle the reaction mixture in excess petroleum ether , after separation, washing, recrystallization and drying, L-phenylalanine-N-cyclic acid anhydride is obtained.

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Abstract

The invention provides nano-gel, a preparation method thereof and anti-tumor drug-loading nano-gel. The provided nano-gel is as shown in a formula (1), wherein m, x, y and n refer to polymerization degrees, 40<=m<=120, 1<=x<=50, 1<=y<=50 and 1<=n<=50. CPPs are membrane penetration peptide modified groups, and the tail ends of the membrane penetration peptide modified groups are semi-finished glycine. According to the nano-gel with a structure as shown in the formula (1), the nano-gel serves as an anti-tumor drug carrier, targeted enrichment can be implemented a tumor, adhesiveness and deep penetration for tumor cells can be improved, drug-loading particles are easily taken by tumor cells, the nano-gel has response sensibility, a disulfide bond in the structure can be rapidly broken under the high glutathione concentration in the tumor cells, drugs in the tumor cells are intelligently released, targeting-endocytosis-releasing combined actions are achieved, and anti-tumor effects are improved.

Description

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Claims

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Application Information

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Owner CHANGCHUN INST OF APPLIED CHEMISTRY - CHINESE ACAD OF SCI
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