Chitosan-containing formulations and methods of making and using the same

Abstract

Provided herein are chitosan-containing formulations, methods of making such formulations, and methods of using such formulations. Chitosan contemplated for use herein is preferably of high quality and its source is preferably of crustacean origin. The formulations contemplated herein are aqueous, either liquid- or viscous-like, varying in concentration and type of chitosan and acid used, and may include other components. Their uses are diverse, for oral/dental administration or topical/surface application to subjects (e.g. humans or animals) in need thereof or even food commodities, aiming to maintain a good condition where it is applied or contributing to health enhancement, healing, disease prevention or treatment. The present invention also relates to concentrated solutions that may be used for the formulation of other products.

What is claimed is: 
     
         1 . An aqueous chitosan-containing formulation comprising:
 chitosan,   an amount of at least one acid effective to enhance the solubility of said chitosan in deionized water, and   an amount of deionized water effective, in the presence of said acid, to solubilize said chitosan,   
       wherein said aqueous chitosan-containing formulation is suitable for administration to a subject in need thereof. 
     
     
         2 . The formulation of  claim 1  wherein 1% of the chitosan on a dry basis, in 1% acetic acid, has a Brookfield rotational viscosity at 25° C. from about 5 cps to about 2,000,000 cps. 
     
     
         3 . The formulation of  claim 1  wherein the chitosan is present at a concentration of between about 0.1% and about 10% by weight based on the weight of said formulation. 
     
     
         4 . The formulation of  claim 1  wherein the percentage of deacetylation of said chitosan is up to 100%. 
     
     
         5 . The formulation of  claim 1  wherein the chitosan is of crustacean origin. 
     
     
         6 . The formulation of  claim 1  wherein the chitosan has a moisture content of <15%; an ash content <1%, a turbidity of <50 NTU, a solubility of >99% and <3 ppm heavy metals (i.e., As, Cd, Pb, Hg). 
     
     
         7 . The formulation of  claim 1  wherein the deionised water comprises at least 80 wt % of the solution. 
     
     
         8 . The formulation of  claim 1  wherein the deionized water is USP purified water with TDS<1 ppm, an electrical conductivity <1.3 μS/cm (®25° C.) and TOC<0.50 ppm. 
     
     
         9 . The formulation of  claim 1  wherein the amount of acid effective to solubilize said chitosan is at least about 10% percent of the weight of the chitosan with which the acid is mixed. 
     
     
         10 . The formulation of  claim 9  wherein the acid effective to solubilize said chitosan comprises from about 40% up to 100% of the weight of the chitosan with which the acid is mixed. 
     
     
         11 . The formulation of  claim 1  wherein the acid is an organic acid. 
     
     
         12 . The formulation of  claim 11  wherein the organic acid is an aliphatic or aromatic organic acid having in the range of about 2 up to 10 carbon atoms. 
     
     
         13 . The formulation of  claim 11  wherein the organic acid is selected from the group consisting of glycolic acid, acetic acid, malic acid, citric acid, ascorbic acid, succinic acid, and lactic acid, or a mixture of any two or more thereof. 
     
     
         14 . The formulation of  claim 13  wherein the organic acid is lactic acid. 
     
     
         15 . The formulation of  claim 1  having a pH of <6. 
     
     
         16 . The formulation of  claim 1  having a pH in the range of about 3-5.9. 
     
     
         17 . The formulation of  claim 1  wherein the solution is substantially free of compounds that form insoluble complex(es) with chitosan, potentially inducing the precipitation thereof. 
     
     
         18 . The formulation of any one of the preceding claims further comprising:
 (i) one or more plasticizers to favor a smooth, elastic and well performing seal on the skin;   (ii) one or more essential oils to enhance the inherent biological activity;   (iii) one or more iodophors to enhance the antimicrobial spectrum;   (iv) one or more preservatives and/or stabilisers to enhance product stability;   (v) honey; and/or   (vi) mixtures of any two or more thereof.   
     
     
         19 . An aqueous chitosan-containing formulation comprising:
 chitosan,   an amount of at least one acid effective to enhance the solubility of said chitosan in deionized water,   an amount of deionized water effective, in the presence of said acid, to solubilize said chitosan, and   at least one polyol.   
     
     
         20 . The aqueous chitosan-containing formulation of  claim 19  wherein said polyol is selected from glycerol, PPG, PEG, maltitol, sorbitol, or xylitol. 
     
     
         21 . The aqueous chitosan-containing formulation of  claim 19  wherein said polyol has a molecular weight in the range of about 90-1000 g/mol. 
     
     
         22 . The aqueous chitosan-containing formulation of  claim 19  wherein the concentration of said polyol falls in the range of about 0.1-10%. 
     
     
         23 . A method of producing an aqueous chitosan-containing formulation, said method comprising mixing chitosan with an amount of acidified deionised water effective to solubilize said chitosan. 
     
     
         24 . A method of producing an aqueous chitosan-containing solution having a Brookfield rotational viscosity of about 5 cps to 750 cps resulting in a homogeneous, easily sprayable solution, said method comprising:
 mixing about 0.5% up to about 10% chitosan with an amount of acidified deionised water effective to solubilize said chitosan, wherein said chitosan has:
 a weight-average molecular weight of from about 20,000 Daltons to about 500,000 Daltons; 
 an apparent viscosity of at least about 5 cps, and 
 a percentage of deacetylation of about 70% to 100%; 
   solubilising said chitosan for at least 30 minutes at 60° C., and   optionally sterilizing and/or clarifying the resulting composition before packaging.   
     
     
         25 . The method of  claim 24  wherein said clarification is accomplished by filtering through at least 30-micron filters. 
     
     
         26 . The method of  claim 24  wherein said sterilization is accomplished by heating or irradiation. 
     
     
         27 . The method of  claim 24  wherein the chitosan solution may be prepared as a basic formulation for cosmetic and/or personal care applications to:
 (i) cover and protect as a film-forming ingredient to favour moisture control; 
 (ii) provide antimicrobial activity as a natural biopreservative; and/or 
 (iii) act as a carrier of other active ingredients for slow release, due to ionic bonding to compounds and chitosan degradation by natural skin enzymes. 
 
     
     
         28 . The chitosan solution prepared by the method of any one of  claims 24 - 27 . 
     
     
         29 . A method of producing a chitosan solution having a Brookfield rotational viscosity in the range of about 1000 cps up to about 20,000,000 cps resulting in a homogeneous gel-like product, said method comprising:
 mixing about 0.5% up to about 5% chitosan with an amount of acidified deionised water effective to solubilize said chitosan,   wherein said chitosan has
 a weight-average molecular weight of from about 200,000 Daltons to about 2,000,000 Daltons; 
 an apparent viscosity of at least about 100 cps and 
 a percentage of deacetylation of from about 70% to 100%; 
   solubilising said chitosan for at least 30 minutes at 60° C., and   optionally filtering through at least 30-micron filters, and   optionally sterilizing the resulting composition before packaging.   
     
     
         30 . The method of  claim 29  wherein the homogeneous chitosan gel-like solution may be applied to
 (i) cover, seal and/or protect a wound or injured/inflammed skin or area; 
 (ii) result in a smooth and tailor-made film, easily shaped to the skin or area under treatment, that, optionally, is degraded by skin enzyme(s); 
 (iii) provide the appropriate conditions for moisture control; 
 (iv) control skin and wound infections; 
 (v) reduce itching and inflammation; 
 (vi) contribute to rapid healing; 
 (vii) reduce scar formation; 
 (viii) relieve aches and pains related to sore muscles and joints; and/or 
 (ix) treat disorders within the oral mucosa and tooth supporting tissues. 
 
     
     
         31 . The chitosan solution prepared by the method of  claim 29  or  30 . 
     
     
         32 . A method for treating a skin condition in a subject in need thereof, said method comprising applying an effective amount of a solution according to any one of  claims 1 - 22  to the skin of said subject. 
     
     
         33 . A method for treating a skin condition in a subject in need thereof with chitosan, wherein the chitosan is applied in the form of a solution which may be applied by spraying or dipping to:
 (i) help clean dirty wounds and contribute to rapid healing of humans and animals;   (ii) cover and protect superficial wounds or temporary skin defects/damage/irritation/inflammation and promote healing;   (iii) provide a sealing and protective barrier with antimicrobial properties and that maintains optimal moisture level;   (iv) reduce skin inflammation due to insect bites, plant poison, sunburns, bedsores, etc.;   (v) strengthen the skin natural protection and better withstand friction and related dryness;   (vi) promote natural microbiota of skin and reduce undesirable microorganisms; and/or   (vii) result in a smooth and tailor-made bandage-like film that will be degraded by skin enzyme(s),   
       said method comprising applying, by spraying or dipping, an effective amount of a solution according to  claim 28  to the skin of said subject. 
     
     
         34 . A method for enhancing muscle, skin, dental, ear, eye and digestive health in animals and humans, said method comprising applying an effective amount of a solution according to any one of  claims 1 - 22 ,  28  or  31 . 
     
     
         35 . A method of producing an aqueous chitosan-containing solution having a Brookfield rotational viscosity of about 50 cps to 50,000 cps resulting in a homogeneous, easily applicable solution, said method comprising:
 mixing about 0.5% up to about 10% chitosan with an amount of acidified deionised water effective to solubilize said chitosan, wherein said chitosan has:
 a weight-average molecular weight of from about one hundred thousand Daltons to about five hundred thousand Daltons; 
 an apparent viscosity of at least about 10 cps, and 
 a percentage of deacetylation of about 70% to 100%; 75-100%; 80-100%; 85-100%; 90-100% 
   solubilising said chitosan for at least 30 minutes at 60° C., and   optionally filtering through at least 30-micron filters, and   optionally sterilizing the resulting composition before packaging.   
     
     
         36 . A method for rinsing a perishable food commodity with chitosan prior to processing, wherein the chitosan is prepared in the form of a solution that may be diluted before application to:
 (i) achieve a reduction of the inherent surface contamination of the food commodity;   (ii) reduce microbial transfer from the raw material to the processing equipment;   (iii) better control the hygienic standard required during food processing; and/or   (iv) promote quality and safety of the food processed,   
       said method comprising applying the processing aid by rinsing the food commodity with an effective amount of the solution according to any one of  claims 1 - 22  or  35 . 
     
     
         37 . A method for coating a perishable food commodity with chitosan, wherein the chitosan is prepared in the form of a solution that may be applied by spraying or dipping to:
 (i) help reduce inherent surface contamination of food commodity;   (ii) cover and protect food commodity as long as necessary, hence reducing water loss and oxidative changes during storage time;   (iii) provide an antimicrobial barrier to retard growth of spoilage and pathogenic microorganisms until removed by washing or deskinning or until degraded by surface enzymes; and/or   (iv) extend the freshness period, thereby enhancing food quality as well as food safety,   
       said method comprising applying, by spraying or dipping, an effective amount of a solution, as a processing aid, according to any one of  claims 1 - 22  or  35  on food commodity surface.