GB2454221A - Chemically modified chitosan as an anticancer agent - Google Patents

Chemically modified chitosan as an anticancer agent Download PDF

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Publication number
GB2454221A
GB2454221A GB0721438A GB0721438A GB2454221A GB 2454221 A GB2454221 A GB 2454221A GB 0721438 A GB0721438 A GB 0721438A GB 0721438 A GB0721438 A GB 0721438A GB 2454221 A GB2454221 A GB 2454221A
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GB
United Kingdom
Prior art keywords
chitosan
chemically modified
treatment
natural polymer
water soluble
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
GB0721438A
Other versions
GB0721438D0 (en
Inventor
Mohamed Abdelhafez El-Far
Mohamed Elshal
Ibrahim El-Shesbimy
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Individual
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Priority to GB0721438A priority Critical patent/GB2454221A/en
Publication of GB0721438D0 publication Critical patent/GB0721438D0/en
Publication of GB2454221A publication Critical patent/GB2454221A/en
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A61K31/722—Chitin, chitosan
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
    • C08B37/0024—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid beta-D-Glucans; (beta-1,3)-D-Glucans, e.g. paramylon, coriolan, sclerotan, pachyman, callose, scleroglucan, schizophyllan, laminaran, lentinan or curdlan; (beta-1,6)-D-Glucans, e.g. pustulan; (beta-1,4)-D-Glucans; (beta-1,3)(beta-1,4)-D-Glucans, e.g. lichenan; Derivatives thereof
    • C08B37/0027—2-Acetamido-2-deoxy-beta-glucans; Derivatives thereof
    • C08B37/003—Chitin, i.e. 2-acetamido-2-deoxy-(beta-1,4)-D-glucan or N-acetyl-beta-1,4-D-glucosamine; Chitosan, i.e. deacetylated product of chitin or (beta-1,4)-D-glucosamine; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
    • C08L5/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L51/00—Compositions of graft polymers in which the grafted component is obtained by reactions only involving carbon-to-carbon unsaturated bonds; Compositions of derivatives of such polymers
    • C08L51/02—Compositions of graft polymers in which the grafted component is obtained by reactions only involving carbon-to-carbon unsaturated bonds; Compositions of derivatives of such polymers grafted on to polysaccharides

Abstract

This invention relates to the proficient anticancer activity of a chemically modified natural polymer, chitosan. Chitosan has been converted through to a water soluble form that shows anticancer activity. The chitosan is preferably modified by carboxymethylation followed by graft copolymerisation with sodium acrylate. The modified chitosan causes G2M phase accumulation as well as induction of apoptosis, resulting in a significant decrease in tumour volume. The modified chitosans may also be used for the treatment of bacterial and viral infections.

Description

1 2454221
THE DESCRIPTION
CHEMICALLY MODIFIED CHITOSAN AS EFFICIENT ANTICANCER
AGENT
This invention relates to the quite proficient anticancer activity of a chemically modified natural polymer, chitosan. Chitosan has been converted through modified procedures to produce a water soluble form that shows this promising anticancer activity.
Chitosan [a (1 -4) 2-amino-2-deoxy-3-D-glucan] is a cationic biopolymer obtained through alkaline N-deacetylation of natural chitin. Chitosan is a biodegradable, non-toxic, biocompatible and environmentally friendly material with many superior properties. However, its poor solubility in water restricts its wide spread utilization.
The carboxymethylation of chitosan is a good mean for conversion of it into a water-soluble form.
Carboxymethyl chitosan has unique chemical, physical and biological properties, particularly its low toxicity and biocompatibility. These unique properties enable it to be used in many medical applications.
In the present invention, chitosan was carboxymethylated through a modified procedure and then further chemically modified in mild aqueous medium via graft copolymerization with different vinyl monomers using a new method. In the current application the monomer used was sodium aciylate at different concentrations and the copolymerisation was achieved by ammonium persulite-induced free radical polymerisation.
All the resulted water soluble chemically modified chitosan polymers were fully characterised by numerous techniques. For instance, FT-IR, elemental analysis, scanning electron microscopy (SEM) and thermal analysis (TGA and DSC).
The preparation of the chemically modified chitosan is shown in the accompanying Figure (Figure 1). In this figure, chitosan (1) has been converted into water soluble carboxymethylated polymer (2) in alkaline medium using chioroacetic acid. Then, the polymer (2) has been further modified through a new method using sodium aciylate (3) to produce the copolymer (4).
Our present invention provides advantages in making our novel chemically modified chitosan as a non-toxic water soluble material in reproducible simple steps with high stability as well as excellent yield product.
The anti-cancer activity of the prepared chemically modified polymers was investigated using mice bearing ehrlich ascites tumour,in different doses of our novel compound dissolved in water,.we have found that our nove chemically modified chitosan can inhibit tumour growth highly significantly in a dose dependent manner. Safe doses found to inhibit the growth of tumour completely and virtually eliminated it,see photographs attached.One for an animal with ehrlich ascites tumour and not treated,and the second photograph for an ehrlich ascites tumour animal treated with our prepared chemically modified poiyiners.This novel application in the treatment of tumour made us study the response of ehrlich ascites tumour cells in-vivo to diflèrent concentrations of our compound,using flow cytometry cell cycle analysis.,which revealed a G2M phase accumulation as well as induction of apoptosis in ehrlich ascites calls associated with highly significantly decrease in tumour volume.
From the results obtained, it is obviously confirmed that the investigated chemically modified chitosan can act as a good candidate of polymeric drugs in the treatment of cancer A preferred embodiment of the invention can be demonstated with reference to the accompanying figure and two photographs in which: Figu1: In this figure, chitosan (1) has been converted into water soluble carboxymethyiated polymer (2) in alkaline medium using chioroacetic acid. Then, the polymer (2) has been further modified through a new method using sodium aciylate (3) to produce the copolymer (4).
Photographs: show that Safe doses found to inhibit the growth of tumour completely and virtually eliminated it,.One for an animal with ehrlich ascites tumour and not treated,and the second photograph for an ehrlich ascites tumour animal treated with our prepared chemically modified chitosan.

Claims (1)

1-A chemically modified natural polymer, chitosan has been established.for the treatment of tumours as safe and effective water soluble anti cancer agent 2-As claimed in claim! the material was obtained where chitosan has been converted, through modified carboxymethylation procedures ibilowed by a further chemical modification in mild aqueous medium via graft copolymerization with different concentrations of sodium aciylate, to produce a water soluble form that shows this promising anticancer activity.
3-A chemically modified natural polymer, chitosan which we prepared,as claimed in claim I or 2 to be used as regulator of tumour cell growth and differentiation causing G2M cell cycle arrest and inducing apoptotic death 4-The use of chemically modified natural polymer, chitosan which we prepared as claimed in any of the preceding claims,for the treatment of any virus or most viral infections as well as to use in treatment of bacterial infections.
5-The use of modified chitosan by grafbng diflrent vinyl monomrs to its backbone as claimed can produce effective anticancer and antiviral and antibacterial agents
GB0721438A 2007-11-01 2007-11-01 Chemically modified chitosan as an anticancer agent Withdrawn GB2454221A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
GB0721438A GB2454221A (en) 2007-11-01 2007-11-01 Chemically modified chitosan as an anticancer agent

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
GB0721438A GB2454221A (en) 2007-11-01 2007-11-01 Chemically modified chitosan as an anticancer agent

Publications (2)

Publication Number Publication Date
GB0721438D0 GB0721438D0 (en) 2007-12-12
GB2454221A true GB2454221A (en) 2009-05-06

Family

ID=38834652

Family Applications (1)

Application Number Title Priority Date Filing Date
GB0721438A Withdrawn GB2454221A (en) 2007-11-01 2007-11-01 Chemically modified chitosan as an anticancer agent

Country Status (1)

Country Link
GB (1) GB2454221A (en)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH05271094A (en) * 1992-03-26 1993-10-19 Fuji Photo Film Co Ltd Cancer metastasis-inhibiting agent using carboxymethylated chitin derivative
WO1998011903A1 (en) * 1996-09-18 1998-03-26 Chicura Coöperatie U.A. Chitosan derivatives for treating malignant tumours
WO2004050100A1 (en) * 2002-12-03 2004-06-17 Bio Syntech Canada Inc. Method for treating a tumor using a thermo-gelling chitosan composition
WO2006088985A1 (en) * 2005-02-17 2006-08-24 Chitogenics, Inc. Method and composition for treatment of a mucosal tissure disorder
US20070031468A1 (en) * 2005-08-04 2007-02-08 Endomedix, Inc. Modified chitosan for vascular embolization
WO2008096547A1 (en) * 2007-02-07 2008-08-14 Yaizu Suisankagaku Industry Co., Ltd. Anti-tumor composition comprising tissue-accumulating chitosan gel

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH05271094A (en) * 1992-03-26 1993-10-19 Fuji Photo Film Co Ltd Cancer metastasis-inhibiting agent using carboxymethylated chitin derivative
WO1998011903A1 (en) * 1996-09-18 1998-03-26 Chicura Coöperatie U.A. Chitosan derivatives for treating malignant tumours
WO2004050100A1 (en) * 2002-12-03 2004-06-17 Bio Syntech Canada Inc. Method for treating a tumor using a thermo-gelling chitosan composition
WO2006088985A1 (en) * 2005-02-17 2006-08-24 Chitogenics, Inc. Method and composition for treatment of a mucosal tissure disorder
US20070031468A1 (en) * 2005-08-04 2007-02-08 Endomedix, Inc. Modified chitosan for vascular embolization
WO2008096547A1 (en) * 2007-02-07 2008-08-14 Yaizu Suisankagaku Industry Co., Ltd. Anti-tumor composition comprising tissue-accumulating chitosan gel

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
Carbohydrate Polymers (2006); Vol 63, pp 89-96, "Effective loading and controlled release of camptothecin by...", Zhu et al *
In Vivo (2005); Vol 19, pp 301-310, "Contribution of chitosan and its derivatives to cancer chemotherapy", Kato et al *

Also Published As

Publication number Publication date
GB0721438D0 (en) 2007-12-12

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WAP Application withdrawn, taken to be withdrawn or refused ** after publication under section 16(1)