EP0666763A1

EP0666763A1 - Wound protecting dressing

Info

Publication number: EP0666763A1
Application number: EP93919367A
Authority: EP
Inventors: Henryk Struszczyk; Olli KIVEKÄS
Original assignee: Novasso Oy
Current assignee: Novasso Oy
Priority date: 1992-09-14
Filing date: 1993-09-14
Publication date: 1995-08-16
Also published as: NO950968L; WO1994006484A1; FI924101A; FI924101A0; FI95207C; FI95207B; AU4962693A; NO950968D0

Abstract

The wound protecting dressing comprises chitosan as base material. The chitosan is microcrystalline chitosan in a gel dispersion form in a composition where the carrier liquid is volatile at body temperature of a human or animal, the microcrystalline chitosan being capable of forming upon volatilizing of the carrier a suitably porous adhesive membrane.

Description

Wound protecting dressing

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 10⁴ - 10⁶, 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. In 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. 317, 1987, "Chitin, Chitosan and Related Enzymes", Academic Press Inc., Orlando, 1984, "Chitin in Nature and Technology", Plenum Press, New York, 1986, Proceedings of 1 - 4 International Conference on Chitin/Chitosan, 1978, 1982, 1986, 1988, Medycyna Lotnieza, vol. 1 (90) , p. 40 (1986) , as well as US Patents 3624201, 3632754, 3911116, 4574150 and 4572906, European Patents 0138385, 0200574, 0291587, Japanese Patents 79100059, 79161525, 60142927, 61141373, 62064803, 62167331, 62170254 and 63090507.

The chitin and chitosan are physiologically compatible bioabsorbable and effective wound-healing accelera¬ tors. Polyaminosaccharides, especially chitosan, having a physiological compatibility with living tissues, combined with their non-trombogenic property, appear to make it a most promising material for prosthetic structural devices of any desired shape and size. 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.

The 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.

Action of chitosan in wound-healing and burn teraphy was described in Neurosurgery, vol. 15. p. 9 (1984) and Polymers in Medicine, Plenum Press, London, 1984. The chitosan in contact with red cell membrane forms

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. On the premise that 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.

SUBSTITUTE SHEET According to the present invention there is provided 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.

According to a preferred embodiment of the invention 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.

According to a preferred embodiment of the invention, 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.

According to a preferred embodiment of the invention 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.

According to a preferred embodiment of the invention 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 10³ - 10⁶, deacety- lation degree not less than 30 %, preferably within a range of 0.01 - lOOμm. Further, it has preferably a medical grade of purity with a heavy metal content

SUBSTITUTE SHEET less than 10 ppm, ash content less than 0.5 wt % and bacteria content according to NF XII and XIV stan¬ dards.

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.

According to a preferred embodiment of the invention, 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.

According to the present invention there is provided 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.

SUBSTITUTE SHEET According to a preferred embodiment of the invention 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.

According to a preferred embodiment of the invention, 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 10³ - 10⁶, deacetylation degree not less than 30 %, preferably 50 - 90 %, particle dimension preferably within a range of 0.01 - 100 μm. The composition has preferably the medical grade of purity mentioned above.

According to a preferred embodiment of the invention 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.

According to a preferred embodiment of the invention, 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.

SUBSTITUTE SHEET According to a preferred embodiment of the invention, 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. .

Properties of the 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.

Application of other film-forming natural polymeric materials, such as sodium and/or calcium alginates or cellulose derivatives such as sodium carboxylmethyl¬ cellulose, into a mixture with microcrystalline chitosan gel-like dispersion improves the behavior and properties of the obtained film such as oxygen per¬ meability, elasticity, tenacity and elongation. At the same time liquid mixture of microcrystalline chitosan

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, according to the invention 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.

SUBSTITUTE SHEET 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.

The following methods of the determination of proper¬ ties of microcrystalline chitosan, other natural polymeric materials as well as the wound protecting dressing have been applied:

- crystalline index IK_j-: according to the infrared method described in the Textile Research Journal, vol. 29, p. 786, 1959

- deacetylation degree of chitosan: according to the infrared method described in the International Journal of Biological Macromolecules, vol. 2, p. 115, 1980

SUBSTITUTE SHEET - energy of hydrogen bonds E_H: according to the infra¬ red method described in the cellulose chemistry and Technology, vol. 7, p. 173, 1973

- water retention value WRV: according to the method described in the Cellulose Chemistry and Technology, vol. 11, p. 633, 1977

- average molecular weight of chitosan: according to the method described in "Chitin", Pergamon Press,

New York, 1977

- medical purity of microcrystalline chitosan: accor¬ ding to the international standards of National Formulation of NF XII and NF XIV

The ingredients used were:

1. 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

2. 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.

3. Ethyl alcohol or diethyl ether as the organic media for microcrystalline chitosan dispersion

4. Propellant for preparation of an aerosol spray or foam in the form of propane-butane fluorocarbo- hydrates or alcohol

SUBSTITUTE SHEET The invention is explained further in the following examples, which do not restrict the scope of claims.

EXAMPLE 1.

100 weight parts of the microcrystalline chitosan gel¬ like dispersion in ethyl alcohol containing 2.5 wt-% of polymer, characterized by WRV of 800 %, average molecular weight of 4.2 * 10⁵, deacetylation degree of 75 %, medical grade of purity, particle dimension within a range of 0.1 - 20 μm, and dispersion reaction pf pH of 7.1. was introduced to a pressure container and 5.5 weight parts of propane-butane mixture was filled.

The 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. 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.

The 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. The

SUBSTITUTE SHEET clinical tests showed that this wound protecting dressing is not allergic and does not make any irrita¬ tion.

EXAMPLE 3.

25 weight parts of the microcrystalline chitosan gel¬ like dispersion in ethyl alcohol containing 1.9 wt-% of polymer, characterized by WRV of 1010 %, average molecular weight of 2.3 * 10⁵, deacetylation degree of 85 %, medical grade of purity, particle dimension within a range of 0.1 - 25 μm, and dispersion reaction of pH of 7.0 was introduced to a pressure container with 3.5 weight parts of propane-butane mixture.

The 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.

The clinical tests showed that this wound protecting dressing is not allergic and does not make any irrita- tion.

EXAMPLE 4.

10 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.

The microcrystalline chitosan aerosol composition was sprayed on a wound to form in 22 seconds a porous, adhesive and elastic chitosan membrane of wound protecting dressing characterized by thickness of 0.04 mm, energy of hydrogen bonds of E_H = 23.7 kJ/mol and

SUBSTITUTE SHEET crystallinity index of IK-- = 0.4. The clinical tests showed that this wound protecting dressing is not allergic and does not make any irritation.

EXAMPLE 5.

28 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 6.0 weight parts of fluorocarbohydrates mixture.

The 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_χ of 0.33. The clinical tests showed that this wound protecting dressing is not allergic and does not make any irritation.

EXAMPLE 6.

30 weight parts of the microcrystalline chitosan gel¬ like dispersion in diethyl ether containing 2.4 wt % of polymer, characterized by WRV of 2100 %, average molecular weight of 2 * 10⁴, deacetylation degree of 87 %, medical grade of purity, particle dimension within a range of 0.1 - 5 μm, and dispersion reaction of pH of 7.0 was introduced into a self-pressure container with 2.0 weight parts of ethyl alcohol.

The 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. The

EXAMPLE 7.

50 weight parts of the 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 * 10⁵, deacetylation degree of 69.5 %, particle dimension in a range of 1 - 20 μm, 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 %.

The 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.

The 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.

EXAMPLE 8.

50 weight parts of the aqueous microcrystalline chitosan dispersion with properties described in

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.

The clinical tests showed that this wound protecting dressing is not allergic and does not make any irrita¬ tion.

EXAMPLE 9.

The 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.

The 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 τκ_τ of 0.10.

The clinical tests showed this wound protecting dressing is not allergic and does not make any irrita¬ tion.

SUBSTITUTE SHEET EXAMPLE 10 .

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. The 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_χ of 0.12.

The clinical tests showed this wound protecting dressing is not allergic and does not make any irrita¬ tion. At the same time antihemosto e effect was observed.

EXAMPLE 11.

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.

SUBSTITUTE SHEET

Claims

Claims :

1. Wound protecting dressing comprising chitosan as base material, characterized in that the chitosan is microcrystalline chitosan in a gel dispersion form in a composition with a carrier liquid being volatile at body temperature of a human or an animal, the microc¬ rystalline chitosan being capable of forming upon volatilizing of the carrier a suitably porous adhesive membrane.

2. Wound protecting dressing as claimed in claim 1, characterized in that the microcrystalline chitosan is contained in a pressure container in a composition together with the carrier and a propellant, such as propane-butane mixture, for use as an aerosol spray or foam on the wounds and surrounding areas.

3. Wound protecting dressing as claimed in claim 1 or 2, characterized in that the carrier liquid contains volatile organic medium such as ethyl alcohol or diethyl ether.

4. Wound protecting dressing as claimed in any of the claims 1 - 3, characterized in that the composi¬ tion before the application contains 0.1 - 10 wt.-% of chitosan in a microcrystalline form and 90.0 - 99.9 wt.-% of neutral agents, such as the carrier liquid and propellant.

5. Wound protecting dressing as claimed in any of the claims 1 - 4, characterized in that the content of composition is such that it after the application on the wound and the surrounding area forms by the volatilization of the carrier liquid a porous adhesive

SUBSTITUTE SHEET membrane containing 60 - 95 wt.-% of chitosan in microcrystalline form, the remainder being mainly water.

6. Wound protecting dressing as claimed in any of the claims 1 - 3, characterized in that the microcrystal¬ line chitosan is in a composition containing another film-forming natural polymeric material such as sodium and/or calcium alginate or a cellulose derivative such as sodium carboxylmethylcellulose.

7. Wound protecting dressing as claimed in claim 6, characterized in that the composition before the application contains 0.05 - 10 wt.-% of chitosan in a microcrystalline form, 0.01 - 10 wt.-% of the other natural polymeric material in a form of solution or dispersion, and 80.0 - 99.94 wt.-% of neutral agents, such as the carrier liquid and propellant.

8. Wound protecting dressing as claimed in claim 6 or 7, characterized in that the content of composition is such that it after the application on the wound and the surrounding area forms by the volatilization of the carrier liquid a porous adhesive membrane con- taining 50 - 95 wt.-% of chitosan in microcrystalline form, the remainder being mainly water and the other natural polymeric film-forming material.

9. Wound protecting dressing as claimed in any of the claims 1 - 8, characterized in that the content of the composition is such that the volatilizing of the carrier liquid from the composition till the film forming takes place in not less than 20 seconds at the temperature of 36 - 38 °C.

SUBSTITUTE SHEET

10. Wound protecting dressing as claimed in any of the claims 1 - 9, characterized in that the microcrys¬ talline chitosan used as the base material in the form of neutral gel dispersion has a water retention value WRV within a range of 500 - 5000 %, average molecular weight within a range of 10³ - 10⁶, deacetylation degree not less than 30 %, preferably 50 - 90 %, particle dimension preferably within a range of 0.01 -

100 urn.

11. Wound protecting dressing as claimed in claim 10, characterized in that the microcrystalline chitosan used has a medical grade of purity with a heavy metals content less than 10 ppm, an ash content less than 0.5 wt.-% and a bacteria content according to NF XII and XIV standards.

12. Wound protecting dressing as claimed in claim 3 and in any of the claims 4 - 11, characterized in that it has been prepared using solvent-exchange with the volatile organic medium, such as ethyl alcohol or diethyl ether, from an aqueous dispersion of the microcrystalline chitosan.

SUBSTITUTE SHEET