Preparation and application of amphiphilic polysaccharide conjugate and medicinal compositions thereof

An amphiphilic polysaccharide and conjugate technology, which is applied in the directions of drug combination, drug delivery, and non-active ingredients medical preparations, etc., can solve the problem that the bridging group connecting the drug and the polymer is not easy to find, and the dose of the drug is insufficient. To achieve the anti-cancer effect, the treatment effect is not optimal and other problems, to achieve excellent biodegradability, excellent biocompatibility, and the effect of avoiding capture

Inactive Publication Date: 2010-08-04
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Some polysaccharide-antineoplastic drug conjugates are currently in the research stage, but these conjugates still have the following defects: the synthesis conditions are relatively harsh; the bridging group connecting the drug and the polymer is not easy to find. When such functional groups are directly condensed, the linking arms used are relatively complex, such as amino acids or polypeptides; the prod...

Method used

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  • Preparation and application of amphiphilic polysaccharide conjugate and medicinal compositions thereof
  • Preparation and application of amphiphilic polysaccharide conjugate and medicinal compositions thereof
  • Preparation and application of amphiphilic polysaccharide conjugate and medicinal compositions thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0054] Embodiment 1: the synthesis of heparin-all-trans retinoic acid

[0055] Take 10mmol all-trans retinoic acid, 12mmol dicyclohexylcarbodiimide (DCC), 15mmol hydroxysuccinimide (NHS), dissolve in 30ml N,N-dimethylformamide, protect from light and nitrogen , reacted in ice bath for 30min, and then rose to room temperature for 24h. After the reaction, the precipitate was filtered off, and a large amount of ethyl acetate was added to wash the precipitate. The filtrate was extracted, the ethyl acetate layers were combined, and the solvent was removed by rotary evaporation to obtain the activated intermediate ester of all-trans retinoic acid. Dissolve 1mmol of all-trans retinoic acid activated intermediate ester in 10ml of dichloromethane, slowly drop into 3mmol / ml of ethylenediamine in dichloromethane solution under ice-bath conditions, and monitor the reaction by thin layer chromatography (TLC method) After completion, the reaction liquid is extracted, the organic layers ar...

Embodiment 2

[0056] Embodiment 2: the synthesis of chondroitin sulfate-all-trans retinoic acid

[0057] Take 10mmol of all-trans retinoic acid, 12mmol of dicyclohexylcarbodiimide (DCC), and 15mmol of hydroxysuccinimide (NHS), dissolve them in 30ml of N,N-dimethylformamide, protect from light and nitrogen, The reaction was carried out in an ice bath for 30 min, and then raised to room temperature for 24 h. After the reaction, the precipitate was filtered off, and a large amount of ethyl acetate was added to wash the precipitate. The filtrate was extracted, the ethyl acetate layers were combined, and the solvent was removed by rotary evaporation to obtain the activated intermediate ester of all-trans retinoic acid. Dissolve 1mmol of all-trans retinoic acid activated intermediate ester in 10ml of dichloromethane, slowly drop into 3mmol / ml of ethylenediamine in dichloromethane solution under ice-bath conditions, and monitor the reaction by thin layer chromatography (TLC method) After complet...

Embodiment 3

[0058] Example 3: Synthesis of Heparin-Methotrexate

[0059] Take 10mmol of methotrexate, 15mmol of dicyclohexylcarbodiimide (DCC), and 15mmol of hydroxysuccinimide (NHS), dissolve them in 20ml of N,N-dimethylformamide, keep away from light, under the protection of nitrogen, and store on ice Bath reaction 30min, then rise to room temperature reaction 24h. After the reaction, the precipitate was filtered off, and a large amount of ethyl acetate was added to wash the precipitate. The filtrate was extracted, the ethyl acetate layers were combined, and the solvent was removed by rotary evaporation to obtain the activated intermediate ester of methotrexate. Dissolve 1mmol of methotrexate activated intermediate ester in 20ml of dichloromethane, slowly drop into 1.5mmol / ml of ethylenediamine in dichloromethane solution under ice-bath conditions, and monitor the reaction by thin layer chromatography (TLC method) After completion, the reaction solution is extracted, the organic layer...

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Abstract

The invention relates to preparation and application of amphiphilic polysaccharide conjugate and medicinal compositions thereof with anti-tumor activity and biodegradability. The conjugate has amphiphilicity by using alkylenediamine as a connecting arm and introducing hydrophobic segmer, namely a carboxyl-containing anti-tumor medicament, on a polysaccharide framework, and are formed into nanometer micelles by self-assembly in water. The invention is characterized in that 1) the anti-tumor medicament is physically coated by a hydrophobic inner core consisting of hydrophobic groups so as to remarkably improve the solubility of the anti-tumor medicament; and 2) the anti-tumor medicament obtained by chemical conjugation and physical coating can jointly achieve treatment effect and improve medicament action. The polysaccharide conjugate and the medicinal compositions thereof can be used for injection, oral administration, external use or mucosa administration. The invention has the advantages of simple preparation method, mature technology, high yield, and suitability for large-scale continuous production.

Description

technical field [0001] The invention belongs to the field of pharmaceutical preparations, and relates to an amphiphilic polysaccharide conjugate having both antitumor activity and biodegradability as a drug carrier, and also relates to a preparation method and application of the conjugate. Background technique [0002] Cancer is one of the major diseases threatening human health. According to the statistics of the World Health Organization, there are currently 24.6 million cancer patients in the world, and almost 7 million people die of cancer every year, and the trend is increasing year by year. [0003] Antineoplastic drugs are one of the main methods of clinical treatment at present. However, most of the existing antineoplastic drugs are insoluble water-soluble small molecular compounds, which have poor oral absorption, low bioavailability, and rapid metabolism in the body. The time to maintain blood drug concentration is relatively short. In order to improve the curativ...

Claims

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Application Information

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IPC IPC(8): A61K47/48A61K9/00A61P35/00A61K47/61
Inventor 周建平姚静侯琳
Owner CHINA PHARM UNIV
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