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Tumor-targeted sound and light power medicine-carrying nanometer nano-micelle, and preparation method and purpose thereof

A drug-loaded nanometer and photodynamic technology, applied in the field of medicine, can solve the problems of increasing the suffering and danger of patients, prone to phototoxic reactions, and wide application limitations, and achieves non-immunogenicity, low preparation cost, and high cytotoxicity. Effect

Inactive Publication Date: 2017-04-05
TIANJIN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, photodynamic therapy faces the following problems: first, the excitation wavelength of most photosensitizers (such as porphyrins) is less than 700nm, and the penetration depth of skin and tissue is only a few millimeters, so it can only treat a few superficial or For very localized tumors, its wide clinical application is greatly limited; second, the metabolism of photosensitizers in normal tissues is slow, and phototoxic reactions are prone to occur, and it needs to be kept away from light for one month after medication, so its application is limited; 3. Photodynamic therapy often requires interventional methods, which increases the pain and danger of patients

Method used

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  • Tumor-targeted sound and light power medicine-carrying nanometer nano-micelle, and preparation method and purpose thereof
  • Tumor-targeted sound and light power medicine-carrying nanometer nano-micelle, and preparation method and purpose thereof
  • Tumor-targeted sound and light power medicine-carrying nanometer nano-micelle, and preparation method and purpose thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0067] 1. Synthesis of doxorubicin / hematoporphyrin nanocomplex (HPD)

[0068] ① Disperse 20 mg of hematoporphyrin (HP, American Strem Chemicals Company) in 10 ml of methanol solution at a concentration of 1 mg / ml, and stir at a speed of 800 rpm for 12 h under strict light-proof conditions to obtain HP dark brown nano-aggregates. Dynamic laser scattering method The detected particle size is 31.2nm, and its transmission electron microscope photo is shown in figure 2 .

[0069] ② Disperse 5 mg of doxorubicin (DOX, Dalian Meilun Biotechnology Co., Ltd.) in 5 ml of methanol solution to make the concentration 1 mg / ml, add 3 times the equivalent of triethylamine and protect from light at 4 °C and 800 rpm Stir for 12h for desalination treatment.

[0070] ③The above DOX solution was slowly added dropwise to the HP solution, and stirred at 800rpm in the dark for 24 hours to obtain a methanol dispersion system of the HPD nanocomposite. The particle size was 68.3nm as detected by the d...

Embodiment 2

[0098] 1. Synthesis of epirubicin / protoporphyrin nanocomplex (PPE)

[0099] ① Disperse 25 mg of protoporphyrin IX (PP, Beijing Bailingwei Technology Co., Ltd.) in 10 ml of methanol solution at a concentration of 2.5 mg / ml, stir at a speed of 800 rpm for 12 h under strict dark conditions, and obtain dark brown PP nano-aggregates. TEM photo see Figure 19 .

[0100] ② Disperse 10 mg of epirubicin (EPB, Dalian Meilun Biotechnology Co., Ltd.) in 5 ml of methanol solution to make the concentration 2 mg / ml, add 3 times the equivalent of triethylamine and avoid Light stirring for 12h, desalination treatment.

[0101] ③The above EPB solution was slowly added dropwise to the PP solution, and stirred at a speed of 800rpm in the dark for 24 hours to obtain a methanol dispersion system of PPE nanocomposites. The particle size detected by the dynamic laser scattering method was 40.6nm. TEM pictures of PPE nanocomposites are shown in Figure 20 .

[0102] 2. Preparation of PEG-PLGA nan...

Embodiment 3

[0108] 1. Synthesis of daunorubicin / hypericin nanocomposite

[0109] ① Disperse 25mg of hypericin (Beijing Bailingwei Technology Co., Ltd.) in 10ml of methanol at a concentration of 2.5mg / ml, and stir at 800rpm for 12h under strict dark conditions.

[0110] ② Disperse 10 mg of daunorubicin (Dalian Meilun Biotechnology Co., Ltd.) in 5 ml of methanol solution to make the concentration 2 mg / ml, add 3 times the equivalent of triethylamine and stir in the dark at 4 ° C and 800 rpm 12h, carry out desalination treatment.

[0111] ③ Add the above-mentioned hypericin methanol solution dropwise to the daunorubicin solution, and stir at 800rpm in the dark for 24 hours to obtain a methanol dispersion system of the nanocomposite. The particle size detected by the dynamic laser scattering method is 35.7nm.

[0112] 2. Preparation of Pluronic F127 nanomicelles loaded with daunorubicin / hypericin nanocomposite

[0113] ①Dissolve 150mg of Pluronic F127 (BASF, Germany) in 50ml of methanol solu...

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Abstract

The invention relates to a tumor-targeted sound and light power medicine-carrying nanometer nano-micelle, and a preparation method and a purpose thereof. The medicine-carrying nanometer nano-micelle is structurally characterized in that porphyrins compounds and anthracyclines chemotherapeutic medicine form a nanometer composition through a pi-pi conjugation effect; and amphiphilic block copolymers with PEO (polyoxyethylene) or PEG (polyethylene glycol) hydrophilic segments cover nanometer compounds through the hydrophobic effect to form a hydrophilic case. The medicine-carrying nanometer nano-micelle is in a regular spherical form, and has the advantages of uniform distribution, stable property and high medicine carrying capacity; the medicine can be conveyed to the tumor focus in the targeted way and can be effectively enriched in the tumor tissue; under the ultrasound (illumination) condition, the treatment effect of the anthracyclines chemotherapeutic medicine on the tumor can be obviously enhanced; and the tumor drug resistance can be effectively reversed. Wide clinic application prospects can be realized in an aspect of combined tumor treatment by a sound (light) power therapy method and chemotherapy.

Description

technical field [0001] The invention relates to a tumor-targeting acoustic and photodynamic drug-loaded nano-micelle as well as a preparation method and application thereof. Specifically, polymer nanomicelles containing polyoxyethylene (PEO) or polyethylene glycol (PEG) shells are used as carriers, through the effective co-loading of porphyrin-based acoustic and photosensitizers and anthracycline chemotherapy drugs, tumor Targeted delivery, controllable release, and the combination of acoustic (or photo) dynamic therapy and chemotherapy to achieve a synergistic effect on tumor therapy belong to the field of medical technology. Background technique [0002] Malignant tumors are one of the most serious diseases that threaten human health and life worldwide. At present, traditional treatment methods such as surgery, chemotherapy, and radiotherapy have not made substantial progress in the treatment of malignant tumors, especially for patients with advanced tumors. The side effe...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K31/704A61K41/00A61K47/34A61K47/55A61P35/00
Inventor 张宁王银松刘洋万国运
Owner TIANJIN MEDICAL UNIV
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