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Nano photosensitive drug taking amphiphilic polysaccharide-folic acid conjugate as carrier and preparation method thereof

An amphiphilic polysaccharide and photosensitizing drug technology, applied in the field of nanophotosensitive drugs and their preparation, can solve the problems of poor anti-tumor effect, low bioavailability, and difficulty in dissolving, and achieves good stability and biocompatibility , The effect of good light intensity stability and easy control

Active Publication Date: 2013-10-16
SHENZHEN INST OF ADVANCED TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, fluorescent probes with photosensitivity are mostly fat-soluble organic substances, and due to their low solubility, it is difficult to dissolve and be absorbed by the body in the water-soluble environment of the human body, and the bioavailability is low, resulting in poor anti-tumor effect

Method used

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  • Nano photosensitive drug taking amphiphilic polysaccharide-folic acid conjugate as carrier and preparation method thereof
  • Nano photosensitive drug taking amphiphilic polysaccharide-folic acid conjugate as carrier and preparation method thereof
  • Nano photosensitive drug taking amphiphilic polysaccharide-folic acid conjugate as carrier and preparation method thereof

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preparation example Construction

[0073] A kind of preparation method of the nano medicine that takes amphipathic polysaccharide-folate conjugate as carrier, comprises the following steps:

[0074] S1. Take the polysaccharide or derivatized polysaccharide, 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) and N-hydroxysuccinimide ( NHS) was dissolved in anhydrous dimethyl sulfoxide, added the derivatized folic acid, and reacted overnight at room temperature under dark conditions, the carboxyl group of the polysaccharide or the carboxyl group formed by derivatization of the polysaccharide and the derivatized carboxyl group formed by the derivatization of folic acid amino group connection to obtain the polysaccharide-folate conjugate solution, after separation and purification, freeze-dry the polysaccharide-folate conjugate solution to obtain a polysaccharide-folate conjugate; the polysaccharide or the derivatized polysaccharide and the The mass ratio of the derivatized folic acid is 1:0.1~1:0....

Embodiment 1

[0125] 1. Dissolve 10g of heparin sodium in 100mL of ultrapure water to form an aqueous solution of heparin sodium, then pass through a cation exchange column, collect the solution after passing through the column, add tri-n-butylamine to adjust the pH to neutral, and freeze-dry to obtain heparin sodium- Tri-n-butylamine complex (expressed as H-tBu);

[0126]2. Dissolve 10g of H-tBu, 25g of succinic anhydride, and 2g of DMAP in anhydrous N'N-dimethylformamide to obtain a mixed solution, react at room temperature for 24 hours, and then put the mixed solution in a dialysis bag with a molecular weight cut off (MWCO) of 3500 After three days of dialysis, take the solution in the dialysis bag and pass it through a cation exchange column, collect the solution after passing through the column, then add tetrabutyl ammonium hydroxide to adjust the pH to neutral, and freeze-dry to obtain derivatized heparin sodium (H-Su) ;

[0127] 3. Take 1g of folic acid and 0.404g of CDI, dissolve i...

Embodiment 2

[0133] 1. Dissolve 10g of dextran, 1g of succinic anhydride, and 1g of DMAP in anhydrous DMSO to obtain a mixed solution, react at room temperature for 12 hours, dialyze the mixed solution in a dialysis bag with a MWCO of 3500 for 3 days, and take the solution in the dialysis bag Freeze drying to obtain derivatized dextran (D-Su);

[0134] 2. Take 1g of folic acid and 0.404g of CDI, dissolve them in 30mL of anhydrous dimethyl sulfoxide and react for 4h, add 0.75mL of ethylenediamine, and react overnight to obtain a derivatized folic acid solution, and then put the derivatized folic acid solution into Added into ethyl acetate, the precipitate was collected by centrifugation, and dried in vacuo to obtain derivatized folic acid (folate-NH 2 ); the volume of ethyl acetate is 10 times the volume of the derivatized folic acid solution;

[0135] 3. Take 2g D-Su, 0.1g EDC.HCL, 0.02g NHS, dissolve in 30mL anhydrous dimethyl sulfoxide for activation, add 0.2g Folate-NH 2 , protected f...

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Abstract

The invention provides a nano photosensitive drug taking amphiphilic polysaccharide-folic acid conjugate as the carrier and a preparation method thereof. The nano photosensitive drug comprises active component particles and solvent, each active component particle has a core shell structure, wherein the inner core is photosensitive drug and the outer shell is amphiphilic polysaccharide-folic acid conjugate. The amphiphilic polysaccharide-folic acid conjugate is formed by the connections of carboxyl of polysaccharide or carboxyl derivated from polysaccharide and amino derivated from folic acid. The nano photosensitive drug has a very good photo-stability in human bodies and a very good compatibility for organisms taking polysaccharide-folic acid as the carrier. Furthermore, the nano photosensitive is harmless to normal skins at the radiation of a certain wave length, so tumors can be eradicated through photo-thermal therapies. The nano photosensitive drug realizes integration of diagnosis and treatment of tumors.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to a nano-photosensitive drug with an amphiphilic polysaccharide-folate conjugate as a carrier and a preparation method thereof. Background technique [0002] The treatment methods for cancer mainly focus on chemotherapy, radiation therapy, and surgical therapy. However, these methods have certain limitations. Treatment failure; surgical treatment generally has a large tissue trauma, and the risk of surgery is high. Therefore, using non-invasive means to specifically kill tumor tissue without harming normal tissue is a scientific problem that needs to be solved urgently. [0003] Optical imaging is an imaging method with high sensitivity and no radiation exposure, which makes it easier to monitor the distribution of cells in vivo in real time. Near-infrared imaging (NIR imaging) wavelength ranges from 700 to 1000 nm, and the tissue penetration depth can reach 4 to 10 cm. A...

Claims

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Application Information

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IPC IPC(8): A61K47/36A61K41/00A61K9/14A61K9/107A61P35/00C08B37/10C08B37/04C08B37/08
Inventor 蔡林涛岳彩霞刘朋
Owner SHENZHEN INST OF ADVANCED TECH
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