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Nano microsphere loading with platinum-containing drugs, hydrogel coated with natural polymers and preparation method and application thereof

A technology of natural polymers and nano-microspheres, applied in the loading field of platinum-based drugs, to achieve high encapsulation efficiency, enhanced anti-tumor effect, and double slow release speed

Inactive Publication Date: 2011-08-03
NANJING UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The use of gelatin-polyacrylic acid composite nanospheres loaded with platinum drugs as a dosage form, and the use of natural polymer hydrogel as the carrier of such drug-loaded nanoparticles to be implanted in the body and attached to the tumor site have not been reported yet.

Method used

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  • Nano microsphere loading with platinum-containing drugs, hydrogel coated with natural polymers and preparation method and application thereof
  • Nano microsphere loading with platinum-containing drugs, hydrogel coated with natural polymers and preparation method and application thereof
  • Nano microsphere loading with platinum-containing drugs, hydrogel coated with natural polymers and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0044] Example 1: Preparation of gelatin-polyacrylic acid composite nanospheres loaded with cisplatin

[0045] In a 500ml stirred reactor, 4 grams of type B gelatin with a number average molecular weight of 50,000 and 1 gram of acrylic acid were dissolved in 200ml of distilled water. Under the condition of stirring, the temperature was raised to 80°C. When the gelatin was completely dissolved, 0.3 g of potassium persulfate was added to the reactor as an initiator. React at 80° C. for 2 hours to obtain a nanoparticle dispersion in water phase. Stop the reaction, lower the system temperature to room temperature and filter. After filtration, put the aqueous dispersion into a dialysis bag (Cut-off molecular weight: 12000) and dialyze for 24 hours to remove unreacted monomers and small molecular inorganic salts in the system. Take 2ml of the solution after dialysis, dilute it to 10ml with distilled water, then add 10mg of cisplatin (cis-diaminodichloroplatinum) to the solution, s...

Embodiment 2

[0046] Example 2: Preparation of gelatin-polyacrylic acid composite nanospheres loaded with cisplatin

[0047] In a 500ml stirred reactor, 2.5 grams of type B gelatin with a number average molecular weight of 20,000 and 1 gram of acrylic acid were dissolved in 350ml of distilled water. While stirring, the temperature was raised to 60°C. When the gelatin was completely dissolved, 0.2 g of potassium persulfate was added to the reactor as an initiator. React at 60° C. for 1 hour to obtain a nanoparticle dispersion in water phase. Stop the reaction, lower the system temperature to room temperature and filter. After filtration, put the aqueous dispersion into a dialysis bag (Cut-off molecular weight: 12000) and dialyze for 24 hours to remove unreacted monomers and small molecular inorganic salts in the system. Take 3ml of the dialyzed solution, dilute it to 10ml with distilled water, then add 4 mg of cisplatin (cis-diaminodichloroplatinum) to the solution, stir at 30°C for 12 hou...

Embodiment 3

[0048] Example 3: Preparation of gelatin-polyacrylic acid composite nanospheres loaded with cisplatin

[0049] In a 500 ml stirred reactor, 5 grams of type A gelatin with a number average molecular weight of 100,000 and 1 gram of acrylic acid were dissolved in 200 ml of distilled water. Under the condition of stirring, the temperature was raised to 90°C. When the gelatin was completely dissolved, 0.6 g of potassium persulfate was added to the reactor as an initiator. The reaction was carried out at 90°C for 4 hours to obtain an aqueous nanoparticle dispersion. Stop the reaction, lower the system temperature to room temperature and filter. After filtration, put the aqueous dispersion into a dialysis bag (Cut-off molecular weight: 12000) and dialyze for 24 hours to remove unreacted monomers and small molecular inorganic salts in the system. Take 1ml of the dialyzed solution, dilute it to 10ml with distilled water, then add 40 mg of cisplatin (cis-diaminodichloroplatinum) to th...

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Abstract

The invention provides a gelatin-polyacrylic acid composite nano microsphere of platinum-containing drugs, wherein, the surface of the nano microsphere is charged gelatin molecules, and the inner part is uncharged polyelectrolyte which is formed by the electrostatic interaction between the gelatin molecules and polyacrylic acid molecules; the platinum-containing drugs form a chemical coordinationeffect with the carboxyl group in the system to combine on the nano microsphere, wherein the mass of the platinum-containing drugs accounts for 5-45% of that of the composite nano microspheres, the content of gelatin accounts for 45-70% of the quality of the composite nano microspheres; the content of polyacrylic acid accounts for 10-25% of the quality of the composite nano microspheres, and the even grain diameter of the nano microspheres is 50-200 nanometers. The gelatin-polyacrylic acid composite nano microsphere loading with platinum-containing drugs can be used for being prepared into natural polymer hydrogel; the hydrogel not only possesses good biocompatibility and can be implanted in vivo and pasted on the position of the tumor in the process of surgical operation, but also can substantially improve the dosage of the platinum-containing drugs without adding the systematic toxic and side effect of drugs due to the characteristics of high drug-loading rate and slow-paced dual slow release of the hydrogel.

Description

technical field [0001] The invention relates to the loading of platinum-based drugs, in particular to gelatin-polyacrylic acid composite nano-microspheres coated with platinum-based drugs and a hydrogel wrapped by natural polymers, as well as a preparation method and application thereof. Background technique [0002] Chemotherapy is one of the important means of treating malignant tumors. Platinum drugs have important application value in the treatment of malignant tumors. The treatment mechanism mainly depends on the cytotoxic effect of platinum chemotherapy drugs on cells. At present, the main clinically used platinum drugs include the traditional platinum preparation cisplatin (cisplatin), carboplatin (also known as carboplatin) and oxaliplatin (also known as oxaliplatin) which replace cisplatin. Platinum drugs are non-specific drugs for the cell cycle, which act on the DNA replication process of cells and damage their cell membranes. They have strong broad-spectrum anti-...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/42A61K47/36A61K47/32A61K9/16A61K9/00A61K31/282A61K31/194A61K33/24A61P35/00B01J13/14
Inventor 蒋锡群丁丹武伟
Owner NANJING UNIV
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