Carrier-free hyperbranched macromolecular polymer and preparation method thereof

A macromolecular polymer, carrier-free technology, which can be used in medical preparations without active ingredients, medical preparations containing active ingredients, and drug combinations, etc. The problem of low drug rate is to achieve the effect of solving the low drug load

Active Publication Date: 2020-02-28
NORTHWESTERN POLYTECHNICAL UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] Document 1 "Xiujuan Xi, Shiqi Hu, Zhuxian Zhou and Youqing Shen et al.Dendrimers with the protocatechuic acid building block for anticancer drugdelivery[J].Journal of Materials Chemistry B,2016,4,5236-5245." A single protocatechuic acid drug is used as a unit to construct a polymer drug with a dendritic morphology. However, the synthetic route of this method is cumbersome and the synthetic method is not simple enough.
[0004] Document 2 "Yajun Huang, Xiaokang Ding, Yu Qi, Bingran Yu and Fu-Jian Xu. Reduction-responsive multifunctional hyperbranched polyaminoglycosides with excellent antibacterial activity, biocompatibility and gene transfectioncapability[J].Biomaterials, 2016,104.3:13 published" A polymer drug with a dendritic morphology is constructed using a single drug of the antibiotic gentamicin, tobramycin or neomycin as a motif, combined with a disulfide bond, but only a single drug is used as a motif, and there is no play a role in the combined treatment of diseases
[0005] Document 3 "Xiaopin Duan, Jisheng Xiao, Qi Yin and Yaping Li et al.Smart pH-Sensitive and Temporal-Controlled Polymeric Micelles for Effective Combination Therapy of Doxorubicin and Disulfiram[J].ACS Nano,2013,7(7):5858- 5869." discloses a combined anti-cancer strategy using two drugs, doxorubicin and disulfiram, but the traditional method of physical coating with carriers leads to the disadvantages of low drug loading rate and unstable drug delivery.

Method used

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  • Carrier-free hyperbranched macromolecular polymer and preparation method thereof
  • Carrier-free hyperbranched macromolecular polymer and preparation method thereof
  • Carrier-free hyperbranched macromolecular polymer and preparation method thereof

Examples

Experimental program
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Effect test

Embodiment 1

[0042] Weigh 250mg of cystamine dihydrochloride and place it in a dry 100ml single-necked flask, add 5ml of methanol and 350mg of triethylamine, and stir for 30min in an ice bath. Weigh 88 mg of di-tert-butyl dicarbonate in a beaker and dissolve it with 10 ml of methanol, drop it into the single-necked flask with a constant pressure dropping funnel, and add 10 ml of deionized water after 5 hours of reaction to terminate the reaction. The reaction solvent was removed by rotary evaporation under reduced pressure, then 30ml of saturated sodium chloride solution was added, extracted three times with 50ml of dichloromethane, and the organic phase was dried with anhydrous sodium sulfate. The resulting solid was directly applied to a silica gel column for separation. The solvent was evaporated to dryness with a rotary evaporator, and dried in a vacuum oven for 2 days to obtain 123 mg of cystamine with a single-terminal tert-butoxycarbonyl-protected amino group as a pale yellow oily l...

Embodiment 2

[0050] Weigh 400mg of cystamine dihydrochloride and place it in a dry 100ml single-necked flask, add 8ml of methanol and 560mg of triethylamine, and stir for 30min in an ice bath. Weigh 140 mg of di-tert-butyl dicarbonate in a beaker and dissolve it with 12 ml of methanol, drop it into the single-necked flask with a constant pressure dropping funnel, add 10 ml of deionized water after 5 hours of reaction to terminate the reaction. The reaction solvent was removed by rotary evaporation under reduced pressure, then 30ml of saturated sodium chloride solution was added, extracted three times with 50ml of dichloromethane, and the organic phase was dried with anhydrous sodium sulfate. The resulting solid was directly applied to a silica gel column for separation. The solvent was evaporated to dryness with a rotary evaporator, and dried in a vacuum oven for 2 days to obtain 196 mg of cystamine with a single-terminal tert-butoxycarbonyl-protected amino group as a light yellow oily liq...

Embodiment 3

[0057] Weigh 500mg of cystamine dihydrochloride and place it in a dry 100ml single-necked flask, add 10ml of methanol and 700mg of triethylamine, and stir for 30min in an ice bath. Weigh 175mg of di-tert-butyl dicarbonate in a beaker and dissolve it with 15ml of methanol, drop it into the single-necked flask with a constant pressure dropping funnel, add 10ml of deionized water after 5h of reaction to terminate the reaction. The reaction solvent was removed by rotary evaporation under reduced pressure, then 30ml of saturated sodium chloride solution was added, extracted three times with 50ml of dichloromethane, and the organic phase was dried with anhydrous sodium sulfate. The resulting solid was directly loaded on a silica gel column for separation, the solvent was evaporated to dryness with a rotary evaporator, and dried in a vacuum oven for 2 days to obtain 257 mg of cystamine with a single-terminal tert-butoxycarbonyl-protected amino group as a pale yellow oily liquid.

[0...

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Abstract

The invention relates to a carrier-free hyperbranched macromolecular polymer and a preparation method thereof. According to the invention, two common hydrophobic medicines, namely methotrexate and chlorambucil, are used as basic elements; structural modification is performed on the two hydrophobic medicines so as to allow the structures of the two medicines to respectively contain dynamic covalentbonds, namely a disulfide bond and an ester bond respectively; then an A2+B3 method is employed for polymerization so as to form the hyperbranched macromolecular polymer; finally, self-assembly is performed so as to obtain a hyperbranched macromolecular drug type carrier-free nano-drug self-delivery system; and therefore, a new thought is provided for construction of a carrier-free nano-drug delivery system, and the problems of low drug loading capacity, high cytotoxicity, high toxic and side effects on organs such as kidneys, insufficient responsiveness and the like of existing hyperbranchedpolymers in the aspect of drug encapsulation are solved.

Description

technical field [0001] The invention belongs to the field of polymer material synthesis and a preparation method of functional medicine, and relates to a carrier-free hyperbranched macromolecular polymer and a preparation method. Background technique [0002] Carrier-free nano-drug delivery system has the advantages of high drug loading, simple preparation strategy, precise structure, stable drug release, etc., and has become the main trend in the development of nano-drugs. Complete removal of inert excipients can not only increase the drug loading to 100%, greatly improving the therapeutic effect, but also effectively avoid the toxicity and immune response caused by the carrier. [0003] Document 1 "Xiujuan Xi, Shiqi Hu, Zhuxian Zhou and Youqing Shen et al.Dendrimers with the protocatechuic acid building block for anticancer drugdelivery[J].Journal of Materials Chemistry B,2016,4,5236-5245." A single protocatechuic acid drug is used as a unit to construct a polymer drug wi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G69/42A61K47/59A61K31/519A61K31/196A61P35/00
CPCC08G69/42A61K47/595A61K31/519A61K31/196A61P35/00A61K2300/00
Inventor 田威刘程飞庞俊李鹏翔李慧鑫
Owner NORTHWESTERN POLYTECHNICAL UNIV
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