Classifications

• • 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
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
  • A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
  • A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
  • A61L15/28—Polysaccharides or their derivatives
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
  • A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
  • A61L26/0023—Polysaccharides
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
  • A61L26/0009—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form containing macromolecular materials
  • A61L26/0052—Mixtures of macromolecular compounds
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
  • A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
  • A61L26/0061—Use of materials characterised by their function or physical properties
  • A61L26/0076—Sprayable compositions

Definitions

• This invention relates to wound protecting dressing containing microcrystalline chitosan.
• Chitosan is partially or totally deacetylated chitin which is also known by its chemical name of poly (N- acetyl-glucosamine) . Chitin forms the hard shell of crustaceans and insects as well as the cell walls of fungi. Chitosan is known by its chemical name of poly (2-deoxy-2-aminoglucose) . The chitin and chitosan manufacture as well as their properties are described in "Chitin", Pergamon Press, New York, 1977.
• Microcrystalline chitosan is a specific physical- chemical form of standard chitosan manufactured by a special aggregation system.
• the product according to the above method described in Journal of Applied Polymer Science, vol. 33, p. 177, 1987 as well as Polish Patent 125995 and Finnish Patent 83426 exists in a form of gel-like dispersion or powder.
• Microcrystalline chitosan obtained by the above methods showed a water retention value WRV in a powder form within a range of 200 - 500 % and in a dispersion form of 500 - 5000 %, suitably the average molecular weight within a range of 10 4 - 10 6 , and the deacetyla- tion degree not less than 30 %.
• Microcrystalline chitosan only in a powder form with a low water retention value not higher than 100 %, obtained by acidic hydrolysis of standard chitosan in organic solvents, is known from Japan Patent Applica ⁇ tion 63182304.
• Finnish Patent 77681 discloses a method for making films from microcrystalline chitosan dispersion especially in an aqueous or organic medium, by pouring
• SUBSTITUTE SHEET on a support, preferably on a fibrous, plastic, glass or metal form, and next by drying and removing from the support.
• the film according to the invention is also formed by filtration of microcrystalline chitosan on a filtration support using reduced pressure.
• Chitin, chitosan and their derivatives were found to be very active in wound healing area.
• human clini ⁇ cal tests carried out on several forms of these polymers, such as powder, chitosan salt solutions, fibres, non-woven fabrics, sponges, coated sutures and adjuncts the acceleration of healing was confirmed by effecting the healing at a faster rate in both slow- healing and non-healing wounds.
• the results of medical tests confirming the effectivity of polyaminosacchari- des as wound-healing accelerators were presented in "Chitin", Pergamon Press, New York, 1977, INFOFISH International, vol. 5, p.
• the chitin and chitosan are physiologically compatible bioabsorbable and effective wound-healing accelera ⁇ tors.
• Chitosan was used also effectively as a treat ⁇ ment for certain types of infections.
• SUBSTITUTE SHEET European Patent Application 0277322 by Wella AG discloses a cosmetic composition for treating hair or skin on a base of N-hydroxypropyl ether derivatives of standard chitosan.
• This composition may be mixed with a propellant, liquefied under pressure, filled into a pressure container and be used as an aerosol spray or foam, or as a hair shampoo.
• European Patent Application 0272472 shows also a suitable cosmetic composition, based on standard chitosan salt and copolymer of acrylic acid and ethacrylol-oxy-ethyl trimethyl ammonium chloride, which is formulated as water/alcohol based solutions, creams, gels, dispersions, emulsions or aerosol sprays.
• Japanese Patent 61073655 discloses a wound protecting membrane using a solution containing anionic or cationic macromolecular compounds selected from xanthan gum, alginic acid, galacturonic acid or standard chitosan salts, polylysine and copolymer of dihydroxyethylaminopropyl and glutamic acid.
• compositions in the form of solutions are sprayed at the wound and the surrounding area.
• the membrane developed had good adhesion to a skin, resulting in protecting the wound and eliminating the need for applying a gauze to the wound.
• Japanese Patent 83247995 discloses also the pharma ⁇ ceutical bandages containing water-soluble standard chitosan salts which can be used for treatment of affected parts of mouth, nasal cavity or vagina.
• SUBSTITUTE SHEET a hemostatic coagulum that withstands arterial pressu ⁇ re in vascular grafts and leads to the growth of a vascularized smooth muscle vessel wall with an endot- helial intima.
• a chitosan used to treat various tissues results in the inhibition of fibroplasma and the regeneration of normal tissue elements.
• the availability of abundant lysozyme at the wound site would gradually break down the chitin or chitosan to the active N-acetyl-D-glucosamine dimer and provide for its sustained release it was decided to explore the use of polyaminosaccharides in the wound-healing.
• the well-known wound protecting dressings contain standard chitosan in the form of organic or inorganic salts soluble in water or diluted organic acids, or derivatives of chitin and chitosan soluble in water or organic solvents. Preparation of chitin or chitosan derivatives needs special complicated technologies as well as brings some problems for processing and purification.
• a standard chitosan saltas soluble in water and diluted organic acids having also acidic reaction, usually with pH 3 - 5, cause an irritation or allergic reaction of wound healing or burned place.
• the standard chitosan salt film formed on a skin does not resist against water and will be easily dissolved into washing water or moisture. This type of dressing needs several repetitions to obtain suitable healing.
• the object of this invention is to provide a wound protecting dressing which can be produced from a composition containing microcrystalline chitosan in a gel-like dispersion form, especially in volatile organic medium such as ethyl alcohol or diethyl ether, mixed possibly with a propellant such as propane- butane mixture, fluorocarbohydrates or alcohol, filled into a pressure container, and used as an aerosol spray or foam at the wounds and the surrounding area.
• a composition containing microcrystalline chitosan in a gel-like dispersion form especially in volatile organic medium such as ethyl alcohol or diethyl ether, mixed possibly with a propellant such as propane- butane mixture, fluorocarbohydrates or alcohol, filled into a pressure container, and used as an aerosol spray or foam at the wounds and the surrounding area.
• the wound protecting dressing formed on a wound as the polymeric dressing which is characterized in that the dressing is microcrystalline chitosan creating a suitably porous adhesive membrane.
• the product before application contains 0.1 - 10 wt % of chitosan in the microcrystalline form and 90 - 99.9 wt & neutral agents such as the propellant, for example propane-butane, fluorocarbohydrates, the volatile organic medium and/or water, possibly under suitable pressure.
• the propellant for example propane-butane, fluorocarbohydrates, the volatile organic medium and/or water, possibly under suitable pressure.
• the product after application on the wound and the surrounding area creates by evaporation of volatile organic medium and/or water the porous, adhesive membrane containing 60 - 95 wt % of chitosan in a microcrystalline form, the remainder being mainly water.
• the evaporation of volatile organic medium and/or water from the product formed at the wounds and the surrounding area takes place in not less than 20 seconds at usual temperatures of human body.
• the microcrystalline chitosan used as the base mate ⁇ rial for wound protecting dressing in the form of a neutral gel-like dispersion has a water retention value WRV within a range of 500 - 5000 %, average molecular weight within a range of 10 3 - 10 6 , deacety- lation degree not less than 30 %, preferably within a range of 0.01 - lOO ⁇ m. Further, it has preferably a medical grade of purity with a heavy metal content
• the wound protecting dressing according to the inven ⁇ tion forms a polymeric membrane upon the drying of the microcrystalline chitosan dispersion.
• This membrane contains 60 - 95 wt % of chitosan in a microcrystalli ⁇ ne polymer form, the remainder being mainly water.
• the microcrystalline chitosan used as the base mate ⁇ rial for wound protecting dressing in the form of gel ⁇ like dispersion is solvent-exchanged with the volatile organic medium such as ethyl alcohol or diethyl ether from an aqueous dispersion of this microcrystalline polymer.
• the object of this invention is also to provide the wound protecting dressing which can be produced from the composition containing microcrystalline chitosan in a gel-dispersion form and other film-forming natural polymeric materials such as sodium and/or calcium alginate, derivatives of cellulose such as sodium carboxylmethylcellulose in the form of solution or dispersion, especially in a volatile organic medium such as ethyl alcohol and/or diethyl ether, mixed possibly with a propellant, such as protane-butane mixture, fluorocarbohydrates or alcohol, filled into a pressure container and used as the aerosol spray or foam on the wounds and the surrounding area.
• a propellant such as protane-butane mixture, fluorocarbohydrates or alcohol
• the wound protecting dressing formed on wound as the polymeric film dressing which is characterized in that the dressing is a mixture of microcrystalline chitosan and other film-forming natural polymeric materials creating a suitably porous adhesive membrane.
• the composition before application contains 0.05 - 10 wt % of chitosan in the microcrystalline chitosan form, 0.01 - 10 wt % of the other natural polymeric materials and 80.0 - 99.94 wt % of a neutral agent such as propellant, ethyl alcohol, diethyl ether and/or water, possibly under suitable pressure.
• a neutral agent such as propellant, ethyl alcohol, diethyl ether and/or water, possibly under suitable pressure.
• the composition contains the microcrystalline chitosan in the form of a neutral gel-like dispersion characte ⁇ rized by water retention value WRV of 500 - 5.000 %, average molecular weight within a range of 10 3 - 10 6 , deacetylation degree not less than 30 %, preferably 50 - 90 %, particle dimension preferably within a range of 0.01 - 100 ⁇ m.
• the composition has preferably the medical grade of purity mentioned above.
• the product containing the microcrystalline chitosan as gel-like dispersion is solvent-exchanged with volatile organic medium as ethyl alcohol or/and diethyl ether from aqueous dispersion of this microc ⁇ rystalline polymer.
• the natural polymeric materials can be introduced to the composition of microcrystalline chitosan before, during and/or after the solvent exchange process.
• the product after the application on the wound and the surrounding area creates by evaporation of the volati ⁇ le organic medium and/or water a porous, adhesive membrane containing 50 - 95 wt-% of chitosan in a microcrystalline form in mixture with the other natural polymeric materials, the remainder being mainly water.
• the evaporation of volatile organic medium and/or water from the product forming a film on the wound area takes place in not less than 20 seconds at a usual temperature of human body.
• the wound protecting dressing according to the inven ⁇ tion in a pharmaceutical aerosol spray or foam formu ⁇ lation represents a mixture of microcrystalline chitosan in a gel-like dispersion form, usually in a volatile organic medium a ethyl alcohol or diethyl ether, possibly containing also the propellant, such as a propane-butane mixture or fluorocarbohydrates or alcohol.
• This formulation containing 0.1 - 10 wt-% of microcrystalline chitosan exists in a neutral form containing free amino groups. .
• microcrystalline chitosan dispersion with a medical grade of purity allows to create the aerosol spray or foam wound protecting dressing.
• the ability of microcrystalline chitosan agglomerates to form a stable dispersion in an aqueous or organic medium as well as their biostability in that form allows to prepare a new type of aerosol dressing unknown up to know containing chitosan.
• Unique beha ⁇ vior of microcrystalline chitosan dispersion forms on the skin a suitable adhesive polymeric membrane being a wound protecting dressing without any additional processes except simple drying.
• microcrystalline chitosan gel-like dispersion improves the behavior and properties of the obtained film such as oxygen per ⁇ meability, elasticity, tenacity and elongation.
• SUBSTITUTE SHEET with other natural polymeric material is characterized by better viscosity and film-forming behavior.
• the film covering a wound is characterized also by other useful properties such as higher ability to break a hemostome in the case of a product containing calcium alginate.
• the wound protecting dressing does not cause any irritation or allergic reaction on the skin, wound and surrounding area.
• the composition according to the invention contains only natural biodegradable polymer in a form of microcrys ⁇ talline chitosan as well as organic medium, such as ethyl alcohol or diethyl ether acceptable by human organism, with a neutral pH.
• the wound protecting dressing according to the inven ⁇ tion after application create on a skin, wound and surrounding area a porous, oxygen permeable membrane which protect a wound against infection and other outside threats.
• a wound that can be healed with the dressing can originate from injure, surgical action, burn etc.
• the wound protecting dressing covers all places of wound and surrounding area with an adhesive membrane which is an elastic, biodegradable polymeric film subjected to biodegradation by enzymes from human body.
• the microcrystalline chitosan-based wound protecting dressing is known to be readily attacked by chitinase enzymes, notally by lysozyme which is transported on the wound sites by the inflammatory cells - polymorphonuclear leucocytes.
• the lysozyme at the wound site gradually break down the chitosan to the active N-acetyl-D-glucosamine dimer and provide for its sustained release.
• the wound protecting dressing is water resistant and resistant to washing. High elasticity of this wound protecting dressing as well as their good mechanical properties allows to apply this dressing for every types of wound on human body, especially on special places as hands, legs etc.
• the wound protecting dressing according to the invention forms a polymeric membrane, which is characterized by energy of hydrogen bonds within a range of 10 - 20 kJ/mol.
• the wound protecting dressing according to the inven ⁇ tion formed by drying from a mixture containing the microcrystalline chitosan dispersion needs for creati ⁇ on of a suitable membrane in the minimum 20 seconds, especially 20 - 60 seconds.
• the wound protecting dressing according to the inven ⁇ tion in a form of microcrystalline chitosan dispersion is stable at least one year.
• the object is further to develop the wound protecting dressing on a base of microcrystalline chitosan that can be used in medicine, pharmacy or cosmetic areas.
• Microcrystalline chitosan gel-like dispersion obtained according to Polish Patent 125995.
• Microcrystalline chitosan dispersion was prepared also in an organic medium such as ethyl alcohol or diethyl ether by a solvent exchange procedure
• Film-forming natural polymeric materials such as sodium alginate, calcium alginate or sodium carboxylmethylcellulose in a form of powder creating suitable solutions or also dispersions in a mixture with the microcrystalline chitosan gel-like dispersion.
• microcrystalline chitosan aerosol composition was sprayed on a wound to form in 207 seconds a porous adhesive and elastic chitosan membrane characterized by bonds E H of 20.8 kJ/mol and crystallinity index IK j of 0.38.
• bonds E H of 20.8 kJ/mol and crystallinity index IK j of 0.38 The clinical tests showed that this wound protecting dressing is not allergic and does not make any irritation.
• Example 2 50 weight parts of the microcrystalline chitosan gel ⁇ like dispersion in ethyl alcohol with properties as in Example 1 was introduced to a pressure container with 4.0 weight parts of propane-butane mixture.
• microcrystalline chitosan aerosol composition was sprayed on a wound to form in 62 seconds a porous, adhesive and elastic chitosan membrane characterized by thickness of 0.05 mm, energy of hydrogen bonds E H of 9.3 kJ/mol and crystallinity index IK j of 0.05.
• microcrystalline chitosan aerosol composition was sprayed on a wound to form in 33 seconds a porous, adhesive and elastic chitosan membrane of wound protecting dressing characterized by thickness of 0.08 mm, energy of hydrogen bonds E H of 19.4 kJ/mol and crystallinity index IK j of 0.7.
• microcrystalline chitosan aerosol composition was sprayed on a wound to form in 110 seconds a porous, adhesive and elastic chitosan membrane of wound protecting dressing characterized by thickness of 1.2 mm, energy of hydrogen bonds E H of 20.1 kJ/mol and crystallinity index IK ⁇ of 0.33.
• the clinical tests showed that this wound protecting dressing is not allergic and does not make any irritation.
• microcrystalline chitosan aerosol foam-like composition was sprayed on a wound to form in 95 seconds a porous, adhesive and elastic chitosan membrane of wound protecting dressing characterized by thickness of 1 mm, energy of hydrogen bonds E H of 8 - 10 kJ/mol and crystallinity index IK j of 0.1.
• microcrystalline chitosan gel ⁇ like dispersion in water characterized by polymer content of 3.27 wt %, water retention value of 1.280 %, average molecular weight of 1.28 * 10 5 , deacetylation degree of 69.5 %, particle dimension in a range of 1 - 20 ⁇ m, dispersion reaction of pH of 7.0 and medical grade of purity was double times solvent- exchanged using every time 100 volume parts of ethanol and one time diethyl ether solvent exchanged using 100 volume parts of diethyl ether. Then the polymer was filtered obtaining a polymer concentration of 425 wt %.
• microcrystalline chitosan was introduced into the self-pressure containers with 25 volume parts of mixture of ethyl alcohol with diethyl ether in a volume ratio of 1:1.
• microcrystalline chitosan aerosol foam-like composition was sprayed on a wound to form in 75 seconds of a porous, adhesive and elastic chitosan film covering the wound and surroundings area, charac ⁇ terized by thickness of 0.8 mm, energy of hydrogen bonds E H of 12 kJ/mol and crystallinity index IK j of 0.28.
• the clinical tests showed that this wound protecting dressing is not allergic and does not make any irritation.
• SUBSTITUTE SHEET Example 7 was mixed for 2 hours with 0.16 weight parts of sodium alginate and next the mixture obtained was homogenized with 500 r.p.m. for 5 minutes.
• the microc ⁇ rystalline chitosan mixture with sodium alginate was introduced into the self-pressure containers with 50 volume parts of diethyl ether.
• the product was sprayed on wound to form in 30 seconds of the porous, very elastic and adhesive film covering the wound area with thickness of 0.2 mm, energy of hydrogen bonds E H of 15 kJ/mol and crystallinity index IK j of 0.08.
• microcrystalline chitosan aqueous dispersion mixture with sodium alginate as described in Example 8 was introduced to the pressure containers with 8 weight parts of propane-butane mixture.
• microcrystalline chitosan-alginate composition was sprayed on wound forming in 50 seconds of the porous, very elastic and adhesive film protecting the wound area characterized by thickness of 1.0 mm, energy of hydrogen bonds E H of 16.2 kJ/mol and crystallinity index ⁇ ⁇ of 0.10.
• Example 7 50 weight parts of the aqueous microcrystalline chitosan dispersion with properties described in Example 7 was subjected to solvent-exchange procedure using 100 ml of ethyl alcohol. Then the 1.45 weight parts of powdered calcium alginate was added with stirring for 3 hours and homogenizing with 1.000 r.p.m. for 10 minutes. The product characterized by 5.2 wt % of dry content was introduced into the self- pressure containers with 10 volume parts of ethyl alcohol.
• microcrystalline chitosan-alginate composition was sprayed on wound to form in 68 seconds a porous, very elastic film of chitosan containing calcium alginate characterized by thickness of 0.5 mm, energy of hydrogen bonds E H of 14.8 kJ/mol and crys ⁇ tallinity index IK ⁇ of 0.12.
• Example 7 50 weight parts of the aqueous microcrystalline chitosan dispersion with properties described in Example 7 was subjected to solvent-exchange procedure as in Example 10. Next the 1.50 weight parts of sodium carboxylmethylcellulose of ethanol soluble grade was mixed for 4 hours and homogenized with 800 r.p.m. for 15 minutes. The product characterized by 6.2 wt % of dry content was introduced into the self-pressure containers with 50 volume part of ethanol.
• SUBSTITUTE SHEET The product was sprayed on wound to form in 45 seconds a porous, very elastic and adhesive film with 0.5 mm of thickness, energy of hydrogen bonds E H of 17.8 kJ/mol and crystallinity of 0.30.

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Cited By (10)

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• 1992
  • 1992-09-14 FI FI924101A patent/FI95207C/fi active
• 1993
  • 1993-09-14 WO PCT/FI1993/000364 patent/WO1994006484A1/en not_active Application Discontinuation
  • 1993-09-14 AU AU49626/93A patent/AU4962693A/en not_active Abandoned
  • 1993-09-14 EP EP93919367A patent/EP0666763A1/de not_active Withdrawn
• 1995
  • 1995-03-14 NO NO950968A patent/NO950968D0/no unknown

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