Highly biocompatible dual thermogelling chitosan/glucosamine salt compositions

A technology of chitosan and biocompatibility, applied in the field of chitosan solution, can solve problems such as hydrogel that cannot be turned into homogeneous, rise and the like

Active Publication Date: 2013-07-03
OLIGO MEDIC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although a slight improvement was provided by using polyoses or polyols instead of 1,3-propanediol, as disclosed in U.S. Patent Application No. 2009 / 0004230, the toxicity issue remained unresolved, so this system is unlikely to be useful for cell suitable matrix for sensitive proteins or living tissue
[0012] It is also known that bicarbonates such as NaHCO 3 A solution (a weak base) that can be used to raise the pH of a chitosan solution around 6.5 without causing any precipitation, but the resulting solution cannot become homogeneous in the temperature range of 0 to 50 °C Hydrogels

Method used

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  • Highly biocompatible dual thermogelling chitosan/glucosamine salt compositions
  • Highly biocompatible dual thermogelling chitosan/glucosamine salt compositions
  • Highly biocompatible dual thermogelling chitosan/glucosamine salt compositions

Examples

Experimental program
Comparison scheme
Effect test

Embodiment I

[0073] Preparation of chitosan-buffer solution mixture

[0074] 1. Preparation of Chitosan Solution

[0075] Chitosan solutions (2.00% w / v) were prepared by dissolving medical grade chitosan with medium molecular weight in aqueous HCl. HCl compared to chitosan amino groups (NH 2 ) ratio (referred to as the degree of protonation of chitosan in solution) was maintained at 70%. This solution was sterilized at 121° C. for 30 minutes using an autoclave. After cooling, water loss caused by the autoclave process is compensated for by adding sterile water in a controlled aseptic environment. The solution was then sterile filtered through a metal frit, dispensed in 5.0 mL aliquots and stored at 4°C. An additional aliquot of approximately 3 mL was used to measure the pH of the chitosan solution. The properties of 100 mL solutions prepared using chitosan with a DDA of approximately 80% and 98% are summarized in Table 1.

[0076] Table 1

[0077] Properties of Chitosan Solution (...

Embodiment II

[0102] Preparation of thermal gelation solutions of chitosan using glucosamine-6-phosphate

[0103] Chitosan solutions (-2.0% w / v) were prepared as described in Example I above. The thermogelling solution was prepared by mixing 5.0 mL of chilled chitosan solution with 0.5 mL of chilled glucosamine-6-phosphate disodium salt solution (1M) in an ice bath (~4°C) with vigorous stirring. preparation. The resulting solution with a pH of about 7.0 was then removed from the ice bath and placed at 37°C where it gelled within 15 minutes.

Embodiment III

[0105] Therapeutic procedures using dual thermogelling compositions

[0106] The compositions disclosed herein may be used in minimally invasive therapeutic procedures, especially in musculoskeletal tissues such as articular cartilage, fibrocartilage, and bone, to name a few. The compositions described herein are particularly useful for treating articular cartilage damage and have been used clinically in patients with articular cartilage defects. This composition has been used by orthopedic specialists in accordance with clinical protocols and in accordance with Health Canada's Special Access Program (SAP) for the treatment of knees in patients suffering from knee cartilage damage, knee pain and reduced joint function. Articular cartilage defects in joints.

[0107] A total of nine patients have been treated in Canada, aged 18 to 70 years, with intact knee ligament structures and with one-compartment cartilage damage detected by Magnetic Resonance Imaging (MRI). All patients...

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Abstract

The present disclosure relates to a chitosan solution neutralized with amino-sugar carbonate buffering solution or amino-sugar phosphate buffering solution or phosphorylated aminosugar buffering solution. The resulting themogelling chitosan composition is highly biocompatible, isotonic and has the ability to rapidly turn into gel upon heating to the body temperature. It provides a novel chitosan-based composition to suitable for drug delivery, cell delivery and repair or regeneration of tissues and organs as well as other clinical treatment.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Application Serial No. 61 / 377,592, filed August 27, 2010, and U.S. Provisional Application Serial No. 61 / 444,646, filed February 18, 2011, the specifications of which are incorporated by reference at this. technical field [0003] The description relates to chitosan solutions neutralized with aminosugar carbonate buffer solution, aminosugar phosphate buffer solution or phosphorylated aminosugar buffer solution. Background technique [0004] Hydrogels continue to receive increasing attention as biomaterials for biomedical applications such as tissue engineering and therapeutic agent delivery. Furthermore, those hydrogels that form hydrogels in situ or exhibit a specific ability to increase their viscosity with temperature (also known as thermosensitivity) are preferred over preformed hydrogels because cells and bioactive compounds such as Drugs can be easily mixed w...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08L5/08A61K47/36A61K9/10A61L27/44A61L31/12C08J3/075
CPCA61K9/06A61K47/26A61K47/36A61L27/20A61L27/44A61L27/50A61L27/52A61L27/54A61P17/00A61P19/00A61P19/02A61P21/00A61P25/00A61P41/00C08J3/075C08J2305/08C08L5/08
Inventor 阿代拉蒂夫·陈奈特阿民·塞尔曼尼
Owner OLIGO MEDIC
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