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Tumor-targeted photodynamic medicine carrying nanoparticle as well as preparation method and application thereof

A drug-loaded nanotechnology, tumor-targeting technology, applied in anti-tumor drugs, pharmaceutical formulations, medical preparations with non-active ingredients, etc., can solve problems such as poor targeting ability, chemotherapy resistance, etc. The effect of reversing chemotherapeutic drug resistance and inducing apoptosis

Active Publication Date: 2014-01-29
TIANJIN MEDICAL UNIV CANCER INST & HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In order to overcome the problem of poor targeting and positioning ability of chemotherapy drugs and chemotherapy resistance caused by long-term medication, the present invention provides a tumor-targeted photodynamic drug-loaded nanoparticle that can be directly used in clinical injection applications, its preparation method and use

Method used

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  • Tumor-targeted photodynamic medicine carrying nanoparticle as well as preparation method and application thereof
  • Tumor-targeted photodynamic medicine carrying nanoparticle as well as preparation method and application thereof
  • Tumor-targeted photodynamic medicine carrying nanoparticle as well as preparation method and application thereof

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preparation example Construction

[0054] The preparation method of the tumor-targeted photodynamic drug-loaded nanoparticles has a conjugated structure chemotherapy drug of doxorubicin, or epirubicin, or mitoxantrone.

[0055] In the preparation method of the tumor-targeted photodynamic drug-loaded nanoparticles, the porphyrin or its derivatives are protoporphyrin, or hematoporphyrin, or uroporphyrin, or coproporphyrin.

[0056] The preparation method of the tumor-targeted photodynamic drug-loaded nanoparticle, the molecular weight of the two-terminal amino-terminated isopropyl polyethylene glycol is 2000-6000Da.

[0057] In the preparation method of the tumor-targeted photodynamic drug-loaded nanoparticles, the mass ratio of the chemotherapeutic drug with a conjugated structure to the nano drug carrier is 8:1-1:8.

[0058] In the preparation method of the tumor-targeted photodynamic drug-loaded nanoparticles, the molar ratio of the EDC and NHS of the carboxyl activating group to the carboxyl unit in porphyrin...

Embodiment 1

[0064] 1. Synthesis of hematoporphyrin-polyethylene glycol (HPP) nano drug carrier

[0065] Weigh 22 mg hematoporphyrin, dissolve in 22 mL 2-morpholineethanesulfonic acid (MES) (200 mM, pH=6.0) buffer, stir overnight at room temperature; add 12.6 mg 1-ethyl-(3-dimethylaminopropyl base) carbodiimide hydrochloride (EDC), 7.6 mg N-hydroxysuccinimide (NHS), wherein, the molar ratio of EDC, NHS of the carboxyl activating group to the carboxyl unit in porphyrin or its derivatives is 1:1, activate at room temperature for 5-6h, add 28uL 2-mercaptoethanol to quench EDC;

[0066] Weigh 60 mg of isopropyl polyethylene glycol (NH 2 -PEG-NH 2 ) (molecular weight of 1500) was dissolved in 10 mL of 200 mM phosphate buffer saline (PBS) (200mM, pH =7.5~8.0), the step Use NaOH (1M) to quickly adjust the pH value of the middle solution to 7.5~8.0, transfer it into a constant pressure dropping funnel, control the dropping speed (10s / drop), stir and react overnight, and dialyze with bori...

Embodiment 2

[0091] Synthesis of hematoporphyrin-polyethylene glycol (HPP) nano drug carrier

[0092] Weigh 11 mg of hematoporphyrin, dissolve in 22 mL of MES (200 mM, pH=6.0) buffer, and stir overnight at room temperature. Add 12.6 mg EDC, 7.6 mg NHS and activate at room temperature for 5-6 hours, wherein the molar ratio of EDC, NHS and carboxyl units in porphyrin or its derivatives of the carboxyl activation group is 2:1, add 15 μL 2-mercaptoethanol to quench Extinguish EDC;

[0093] Weigh 30 mg NH2-PEG-NH2 (molecular weight 2500) and dissolve in 10 mL 200 mM PB buffer (200mM, pH =7.5~8.0), and Use NaOH (1M) to quickly adjust the pH value of the middle solution to 7.5~8.0, transfer it into a constant pressure dropping funnel, control the dropping speed (10s / drop), stir and react overnight, and dialyze with boric acid buffer (200mM, pH= 8.5) for 48h (retention Molecular weight 3000 Da). Aqueous dispersion of HPP nanoparticles was obtained. The dispersion was freeze-dried to obt...

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Abstract

The invention discloses a tumor-targeted photodynamic medicine carrying nanoparticle as well as a preparation method and an application thereof, belonging to a medical preparation containing porphyrin or a medical preparation prepared by a method which utilizes wave energy to process materials. According to the invention, porphyrin or derivates of porphyrin of a functional group and polyethylene glycol and polypropylene glycol of a polyether chain segment are connected through chemical bonds or ester bonds or amido bonds of perssads, and then polymerized into a nanoparticle aqueous dispersion of porphyrin or derivates, loaded with a chemotherapy drug with a conjugated structure and dialyzed to obtain the tumor-targeted photodynamic medicine carrying nanoparticle. The nano material prepared by the method is high in yield, regular in shape, uniform in distribution and good in biosecurity, can be effectively loaded with an antitumor drug with a conjugated structure; a water-soluble photosensitizer can effectively reverse drug tolerance of a chemotherapy drug after being irradiated by near-infrared light; the nanoparticle can efficiently target and position tumors, has good anelasticity, effectively inhibits tumor growth, and has a wide application prospect in preparing breast cancer tumor-targeted drugs.

Description

technical field [0001] The invention relates to a medical preparation containing porphyrin, or a medical preparation prepared by using wave energy to process materials, in particular to a tumor-targeted photodynamic drug-loaded nanoparticle and its preparation method and application. Background technique [0002] Chemotherapy is one of the important methods for the treatment of malignant tumors. However, a large number of clinical practices have shown that the drug treatment effect of tumors is not ideal. The reasons mainly include: (1) Chemotherapy drugs have poor selectivity to tumor cells; Chemotherapy drugs not only kill cancer cells, but also damage normal cells of the patient, resulting in severe side effects, which greatly limit the dosage of drugs and seriously affect the therapeutic effect. (2) The multi-drug resistance mechanism of tumor cells; the inherently high expression of ABC proteins (such as P-glycoprotein) on the tumor cell membrane can transport various a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K9/14A61K47/48A61K31/704A61P35/00
Inventor 张宁任玉王银松郭华
Owner TIANJIN MEDICAL UNIV CANCER INST & HOSPITAL
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