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Co-polymer conjugates

A technology of polymers and conjugates, which can be used in drug combinations, medical preparations of inactive ingredients, digestive systems, etc., and can solve problems such as poor bioavailability

Active Publication Date: 2015-04-29
NITTO DENKO CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, like other anticancer drugs, paclitaxel suffers from poor bioavailability due to its hydrophobicity and insolubility in aqueous solutions

Method used

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  • Co-polymer conjugates
  • Co-polymer conjugates
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Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0078] If the preparation of the pharmaceutical formulation involves intimate mixing of a pharmaceutical excipient with the active ingredient in salt form, it may be desirable to use non-basic pharmaceutical excipients, ie acidic or neutral excipients.

[0079] In some embodiments, the pharmaceutical composition may comprise one or more physiologically acceptable surface active substances, carriers, diluents, excipients, lubricants, suspending agents, film-forming substances and coatings. Clothing adjuvants, or combinations of these substances; and compounds disclosed herein (eg, polymer conjugates described herein). Carriers or diluents acceptable for therapeutic use are well known in the pharmaceutical art and are described, for example, in Remington's Pharmaceutical Sciences, 18th Ed., Mack Publishing Co., Easton, PA (1990), which is incorporated herein by reference in its entirety. Preservatives, stabilizers, dyes, sweeteners, fragrances, flavoring agents, etc. may be prov...

Embodiment 1

[0122]

[0123] Can be prepared according to the general route shown in Example 1 containing the structure (Q) Polymer conjugates of repeating units of formula (III).

Embodiment 2

[0125] Partial PGGA Esters - 10% Q

[0126] To PGA-OH (200 mg), EDC (446 mg, 2.33 mmol) and HOAt (317 mg, 2.33 mmol) weighed into an oven-dried vial (40 mL) with a magnetic bar was added 15 mL of anhydrous DMSO. The reaction mixture was stirred at ambient temperature for 2 hours. Glu-diester.HCl (413 mg, 1.40 mmol) and DIEA (243 μL, 1.40 mmol) were added. The mixture was stirred at ambient temperature for 2 h, NH 3 / dioxane (6.2 mL, 0.5M), and the reaction mixture was stirred overnight (16 hours) at ambient temperature. The mixture was slowly poured into 0.2N aqueous HCl to precipitate the polymer. The precipitate was washed with water (2x) and the polymer was isolated by centrifugation. The resulting polymer was frozen and lyophilized to constant weight. Yield 83.3% (446.8mg), GPC (MW: 69.55kDa).

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Abstract

This application relates generally to biocompatible water-soluble polymers with pendant functional groups and methods for making them, and particularly to co-polymer polyglutamate amino acid conjugates useful for a variety of anti-cancer drug delivery applications.

Description

[0001] background technical field [0002] The present application relates generally to biocompatible water-soluble polymers containing pendant functional groups and methods of making them, and in particular to copolymer polyglutamic acids for various drug delivery applications, such as anticancer drugs amino acid conjugates. Background technique [0003] Various systems have been used for the delivery of drugs. Examples of such systems include capsules, liposomes, microparticles, nanoparticles and polymers. Several polyester-based biodegradable systems have been characterized and studied. Some of the best characterized biomaterials with respect to design and performance for drug delivery applications are polylactic acid (PLA), polyglycolic acid (PGA) and their copolymer polylactic-co-glycolic acid (PLGA). See Uhrich, K.E. et al., Chem. Rev. (1999) 99:3181-3198 and Panyam J. et al., Adv Drug Deliv Rev. (2003) 55:329-47. Biodegradable systems based on polyorthoesters have...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/48A61K47/34A61K31/337A61P35/00
CPCA61K49/146A61K47/645A61P1/04A61P11/00A61P13/08A61P15/00A61P17/00A61P35/00C08G69/10
Inventor 曾国贤王海白浩金毅俞磊
Owner NITTO DENKO CORP
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