Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Dextran and arabinogalactan conjugates of therapeutically active compounds

A technology of arabinogalactan and conjugates, which is applied in the field of conjugates of therapeutically active compounds and polysaccharides, and can solve problems such as the reduction of therapeutic effects

Inactive Publication Date: 2009-05-27
HADASIT MEDICAL RES SERVICES & DEVMENT +1
View PDF2 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, a reduction in therapeutic effect is also observed in molecules such as AmB where chemical modifications may also affect the biologically active moiety

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Dextran and arabinogalactan conjugates of therapeutically active compounds
  • Dextran and arabinogalactan conjugates of therapeutically active compounds
  • Dextran and arabinogalactan conjugates of therapeutically active compounds

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0115] Embodiment 1: the synthesis of dextran polyaldehyde

[0116] Dextran with a MW greater than 40,000 was oxidized with varying amounts of periodate to form a range of oxidized dextran with different aldehyde contents (Scheme 1). By adding controlled amounts of potassium periodate (0.0836 g, 0.2875 g, 0.46 g, 0.8625 g, 1.4375 g and 2.875 g, respectively) to 1 g of dextran and stirring for 6 hours at room temperature in a dark container, Thereby, the dextran polyaldehydes with the degree of oxidation ranging from 1.5% to 50% (1.5%, 5%, 8%, 15%, 25% and 50%) were prepared in the aqueous solution. The resulting polyaldehyde was purified from iodate and unreacted periodate ions by Dowex-1 anion exchange chromatography (acetate form, pH 7). Dowex acetate was obtained by pretreatment of a commercially available anion exchanger with 1M aqueous acetic acid. Purified oxidized dextran solution was subjected to 48 h at 4°C against double-distilled water (DDW) (5 L, 4 exchanges) thr...

Embodiment 2

[0122] Example 2: Synthesis of Modified Dextran

[0123] Reduced dextran - Oxidized dextran (1 g, 50% oxidized) was dissolved in 100 mL of DDW. Add NaBH 4 (1 g) and the reaction mixture was stirred for 24 hours. The solution was purified by dialysis and lyophilized (as described in Example 1 above).

[0124] Dextran Acetal - Oxidized dextran (1 g, 50% oxidation) was dissolved in 100 mL of ethanol and stirred for 24 hours. Dextran acetal was precipitated in DDW and lyophilized (as described in Example 1 above).

[0125] Dextran-Ethanolamine Imine / Amine - Dextran (2 g, 50% oxidized) was dissolved in 200 mL of borate buffer (pH 11) and 0.41 mL (1.1 molar equiv.) of ethanolamine was added. The reaction mixture was stirred for 24 hours, after which a 100 mL sample was removed, purified by dialysis, and lyophilized to dryness (as described in Example 1 above) to give the imine form. To get the amine form, add 1 g NaBH 4 into the remaining 100 mL of reaction solution. The reac...

Embodiment 3

[0126] Example 3: Dextran-AmB (AmB) imine / amine conjugates

[0127] In the first step, oxidized dextran was prepared (50% oxidation), followed by the second step, the conjugation of oxidized dextran to AmB (see Reaction Scheme 2). In a typical experiment, 1 g of oxidized dextran with a sugar unit oxidation degree of 50% was dissolved in 100 mL of boric acid buffer (pH=11). AmB powder (0.25 g) was added and the mixture was stirred at room temperature in a dark vessel for 48 hours. The pH of the resulting reaction mixture was maintained at 11 during the reaction. A clear orange-yellow solution of the imine conjugate was obtained, purified by dialysis and lyophilized for 24 hours (as described in Example 1). By adding NaBH to the imine conjugate reaction mixture 4 And the reaction was continued overnight to obtain the amine conjugate. During the course of the reaction, a color change from orange-yellow to light yellow was observed. The amine conjugates were purified by dialy...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
molecular weightaaaaaaaaaa
molecular weightaaaaaaaaaa
molecular weightaaaaaaaaaa
Login to View More

Abstract

The present invention discloses modified polymer conjugates of a polymer and a drug having reduced toxicity relative to the unmodified parent compound while retaining substantially the same degree of therapeutic activity as of the unmodified parent compound.

Description

technical field [0001] The present invention relates to combinations of therapeutically active compounds and polysaccharides. Background technique [0002] For bioactive agents that exhibit limited solubility and stability or have high toxicity, chemical modification by conjugation with hydrophilic polymers such as polysaccharides can be used as an approach to overcome these limitations and reduce the toxicity of the bioactive agents. its toxic means. Other approaches involve formulating bioactive drugs in less toxic forms. One such example is the polyene antibiotic amphotericin B (AmB), which is currently available in the less toxic sodium deoxycholate-AmB micellar form (Fungizone ), as a liposome formulation (AmBisome ), as a colloidal dispersant (Amphotec ) and as a lipoplex (Abelcet )supply. Although the micellar form exhibits overall reduced toxicity, some toxicity to the kidneys, central nervous system, and liver, as well as therapeutic limitations such as lo...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/48
CPCA61K47/4823A61K47/61A61P31/04A61P33/00A61P35/00A61K47/36A61K47/38A61K47/50
Inventor 亚伯拉罕·J·多姆伊扎克·波拉切克玛丽娜·索斯考尔尼雅各布·戈连斯尔
Owner HADASIT MEDICAL RES SERVICES & DEVMENT
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com