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Nucleic acid and hydrophobic chemical medicine double-load self-assembling nano preparation and preparing method thereof

A nano-preparation and self-assembly technology, which is applied in the direction of drug combinations, pharmaceutical formulas, and non-effective components of polymer compounds, can solve the problems of toxic side effects, chemotherapeutic drug resistance, poor selectivity, etc., and achieve controllable preparation Effect

Inactive Publication Date: 2018-06-08
SHANGHAI JIAO TONG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Due to the poor selectivity of chemotherapeutic drugs to cells and the high toxicity and side effects, all anti-tumor chemotherapeutic drugs in clinical use have different degrees of toxic and side effects; long-term use of chemotherapeutic drugs is also prone to drug resistance, so the wide application of chemotherapeutic drugs is subject to certain restrictions. limit

Method used

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  • Nucleic acid and hydrophobic chemical medicine double-load self-assembling nano preparation and preparing method thereof
  • Nucleic acid and hydrophobic chemical medicine double-load self-assembling nano preparation and preparing method thereof
  • Nucleic acid and hydrophobic chemical medicine double-load self-assembling nano preparation and preparing method thereof

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preparation example Construction

[0077] The preparation method of the self-assembled nanometer of the present invention comprises: first loading the chemical drug in the adamantane-modified polyamide-amine to obtain the adamantane-modified polyamide-amine loaded with the chemical drug; The other components are mixed and self-assembled to obtain double-loaded self-assembled nano preparations of nucleic acid and chemical drugs.

[0078] Among them, the adamantane-modified polyamide-amine loaded with chemical drugs can be obtained by a method comprising the following steps: using the hydrophobic cavity inside the adamantane-modified polyamide-amine to physically load the hydrophobic chemical through the solvent evaporation method; drug.

[0079] The adamantane-capped polyethylene glycol can be obtained by a method comprising the steps of attaching adamantane to the end of polyethylene glycol by an amide reaction.

[0080] That is, the amino group on adamantane can be amide-reacted with the carboxyl group on pol...

Embodiment 1

[0089] The synthesis of the poly(ethylene glycol) (Ad-PEG) of embodiment 1 adamantane capping

[0090] For the synthetic formula, see Figure 1A .

[0091] Specifically, Adamantane (Ad). Take by weighing molecular weight and be the adamantane hydrochloride 28.0mg (0.15mmol) of 187.74g / mol, be dissolved in the dichloromethane of 2ml and form a solution, add 15.8mg (0.15mmol) triethylamine as reaction catalyst, add 150mg (MW =5000,0.03mmol) methoxy-polyethylene glycol succinimide, stirred at room temperature for 2h. After the reaction is completed, transfer the reaction liquid to an eggplant-shaped bottle, and distill off dichloromethane under reduced pressure. The white solid is dissolved in 2 mL of double-distilled water and centrifuged at 10,000 rpm for 10 min. The precipitate after centrifugation is unreacted 1-adamantanamine Hydrochloride. The centrifuged supernatant was dialyzed overnight in a dialysis bag of MW 3,500Da, and the dialyzed solution was filtered with a 0.2...

Embodiment 2

[0092] The synthesis of the polyamide-amine (Ad-PAMAM, G5) of embodiment 2 adamantane modification

[0093] 2.1 Synthesis of adamantane-polyamide-amine (Ad-PAMAM, G5)

[0094] For details of the synthetic reaction formula, see Figure 1B .

[0095] Specifically, adamantane, referred to as Ad.

[0096] The polyamide-amine PAMAM used in this example is a fifth generation polyamide dendrimer (PAMAM, G5) with a 1,2-diaminobutane core and amine ends. The polyamidoamine PAMAM is commercially available from Dendritic Nanotechnologies, Inc (Mount pleasant, MI).

[0097] Add 78.86mg (14.74%wt, 2.74umol) of PAMAM (G5) methanol solution into a round bottom flask, carry out vacuum distillation to remove methanol, redissolve the sticky solid in 10mL of dry dimethyl sulfoxide, and dissolve 3.27 1 mg (18.5 mmol) of 1-isocyanoadamantane was dissolved in 10 mL of dry dimethyl sulfoxide, and the dissolved 1-isocyanoadamantane solution was added to the PAMAM (G5) solution, and the reaction w...

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Abstract

The invention belongs to the technical field of biological material, and in particular, relates to a nucleic acid and hydrophobic chemical medicine double-load self-assembling nano preparation and a preparing method thereof. The self-assembling nano preparation includes four molecular modules comprising adamantane-terminated polyethylene glycol, amantadine-modified polyamidoamine, polyethyleneimine-modified beta-cyclodextrin, and nucleic acid and chemical drugs; an amantadine-modified 3-5 generation polyamidoamine hydrophobic cavity is loaded with hydrophobic chemical drugs, and through the charge action and molecular recognition of module molecules, the load of nucleic acid molecules and controllable preparation and long circulation characteristics of the dual-load self-assembling nano preparation are achieved, so as to be used for common load, delivery and combined effect of the nucleic acid molecules and the hydrophobic chemical drugs.

Description

technical field [0001] The invention belongs to the technical field of biological materials, in particular to a double-loaded self-assembled nano preparation of nucleic acid and hydrophobic chemical medicine and a preparation method thereof. Background technique [0002] At present, the incidence of tumors in our country is increasing year by year, and malignant tumors are threatening human life and health. The treatment of malignant tumors mainly includes surgical resection, chemotherapy, radiotherapy, biological immunotherapy and so on. [0003] Among them, chemotherapy is a treatment method that uses chemical drugs to prevent the proliferation, invasion, and metastasis of cancer cells, and finally kill cancer cells. Because chemical drugs kill tumor cells, they also kill normal cells, including immune cells. Due to the poor selectivity of chemotherapeutic drugs to cells and the high toxicity and side effects, all anti-tumor chemotherapeutic drugs in clinical use have di...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/51A61K47/10A61K47/06A61K47/34A61K47/32A61K47/40A61K31/7088A61K45/06A61K31/704A61P35/00
Inventor 彭金良张马鑫于倩茹
Owner SHANGHAI JIAO TONG UNIV
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