WO2012171916A1

WO2012171916A1 - Process and device

Info

Publication number: WO2012171916A1
Application number: PCT/EP2012/061115
Authority: WO
Inventors: Christian Stephenson
Original assignee: Lantor (Uk) Limited
Priority date: 2011-06-14
Filing date: 2012-06-12
Publication date: 2012-12-20
Also published as: GB201109991D0

Abstract

The present invention relates to an anti-microbial component of a absorbent device, to a method for the preparation of such a component, and in particular to a method for the preparation of a novel hydrophilic, anti-microbial derivatised polysaccharide, inter alia in fibrous form, which is loaded with a therapeutically active ionic material, and also to an absorbent fabric and device comprising the component, methods for the preparation of such an absorbent fabric and device, and the use of said absorbent device in a method of treatment or prophylaxis.

Description

Process and Device

The present invention relates to an anti-microbial component of a absorbent device, to a method for the preparation of such a component, and in particular to a method for the preparation of a derivatised polysaccharide, inter alia in fibrous form, which is loaded with a therapeutically active ionic material, and also to an absorbent fabric and device comprising the component, methods for the preparation of such an absorbent fabric and device, and the use of said absorbent device.

The term 'absorbent medical device' as used herein includes wound dressings for acute wounds, including surgical wounds, and chronic and burn wounds, ostomy devices, surgical and dental sponges, and absorbent pads for the personal care sector, particularly for disposable sanitary devices such as nappies (diapers), disposable nappies and training pants, feminine care products, for example, tampons, sanitary towels, or napkins and pant liners, and incontinence products. It in particular includes (but is not limited to) an absorbent medical device comprising as an absorbent material, a water-insoluble partially organic or inorganic acylhydrocarbyl substituted polysaccharide.

The term 'polysaccharide' as used herein means any polymeric carbohydrate structures, formed of repeat monomer units which are mono- or di-saccharides joined together by glycosidic bonds, typically having between 200 and 2500 monomer units in the polymer molecule. They are preferably insoluble in water. These structures include linear homopolysaccharides (in which the monosaccharide monomer units are the same type, and include in particular structural polysaccharides, such as cellulose and chitosan, and derivatives thereof, including those in which the hydroxyl functions on the saccharide repeat unit are derivatised, for example by organic or inorganic acyl residues, and amine addition salts as appropriate.

The term 'partially organic or inorganic acylhydrocarbyl substituted polysaccharide' means a polysaccharide in which one or more of the hydroxyl groups on the monosaccharide or aminomonosaccharide units of the polysaccharide are converted at least in part to HO - R - O - groups (etherification), where HO - R is a hydrocarbyl oxoacid residue, optionally salified preferably with an alkali metal cation. Examples of organic acylhydrocarbyl include carboxymethyl, and examples of inorganic acylhydrocarbyl include sulphonyloxymethyl. Examples of polysaccharides with monosaccharide units include cellulose with glucose units, and examples of polysaccharides with aminomonosaccharide units include chitosan with D-glucosamine units. The other hydroxyl groups on the units of the polysaccharide are often present as hydroxyl group derivatised by base (alkalisation), often with the same alkali metal cation as in any salified HO - R groups that may be present. Either substitution may take place at any hydroxyl position in the polysaccharide, in any distribution up to the maximum degree of substitution that is possible.

By the term 'derivatised polysaccharide' is meant herein a partially organic or inorganic acylhydrocarbyl substituted polysaccharide as defined above. The term Organic or inorganic acyl' as used herein includes organic acid residues such as carboxyl and inorganic acid residues such as sulphonyl.

By the term 'substantially water-insoluble' in the context of a derivatised polysaccharide is meant herein that when it is exposed to an excess of an aqueous medium it does not dissolve into solution, or at least that dissolution is so low as to have no significant effect on the physical properties of the polymer.

The term "ionic" in the context of a therapeutically active material includes materials which are typically salts, preferably acid addition salts of the therapeutically active material, such as amine addition salts, and salified acids, such as salified carboxylic acids.

By the term 'water-soluble' in the context of a therapeutically active ionic material is meant herein that when it is exposed to an aqueous medium it dissolves into solution to at least 1 %, preferably at least 5%, and in particular at least 10% w/w.

By the term 'highly aqueous' in the context of an aqueous medium is meant herein that the medium comprises at least 50%, preferably at least 75%, and in particular at least 85% w/w water. By the term 'loaded derivatised polysaccharide' is meant herein a derivatised polysaccharide as defined above, loaded with a therapeutically active ionic material. It is known to use a partially carboxymethylated modified polysaccharide fibre, tow or yarn in the form of an absorbent non-woven fabric component of a wound dressing. It is also known to add a water-soluble therapeutically active ionic material, such as an anti-microbial, for example polyhexanide (polyhexamethylene biguanide, or PHMB), in general used as its hydrochloride salt, or polyaminopropyl biguanide, PAPB; to polysaccharide fibre, tow or yarn, either in an absorbent device, in particular a medical absorbent device, or for further processing to such a device. .

A first technical problem of the prior art is that a partially carboxymethylated polysaccharide (e.g. chitosan) fibre, tow or yarn or non-woven fabric has a high aqueous absorbency (superabsorbency). If treated with water or a highly aqueous medium, the fibres (per se or within the other forms mentioned) swell in contact with water to become an irreversible gel material, and the dehydration of the product results in a rigid material dissimilar to the original material in physical properties. Neither the gel nor the dehydrated gel fibre, tow or yarn is subsequently processable to a non-woven fabric by conventional techniques, for example by a non-woven technique to an absorbent non-woven fabric component of an absorbent medical device. A gel non-woven fabric cannot be recovered, for example by dehydration.

Such fibres, tow or yarn are therefore usually manipulated in lower-aqueous solvent mixtures during their preparation to avoid over-hydration of the fibres. Typically, isopropanol or ethanol will be a co-diluent that acts as a water-miscible non-solvent for the fibres.

A second technical problem of the prior art is that solvent mixtures comprising such alcohol materials make the process for loading the fibres, tow, yarn and/or a relevant absorbent material with any such additive materials more expensive, besides having safety and toxicity disadvantages, compared with water as a process medium. Only a relatively low loading of the therapeutically active ionic material is achievable with the materials and processes of the prior art as well as a relatively long process time. It is therefore an object of the present invention to provide a derivatised polysaccharide with a relatively high loading of a water-soluble therapeutically active ionic material from a highly aqueous medium, which does not gel irreversibly and is therefore readily processable to an absorbent device component, and thus avoids the disadvantage of the known treatments of partially carboxymethylated polysaccharides with highly aqueous media.

It is also an object of the present invention in overcoming the disadvantage of the prior art to provide a less expensive, safer and also less toxic process, which is capable of providing higher levels of loading of a therapeutically active ionic material in a derivatised polysaccharide than hitherto and/or a shorter process time.

Surprisingly, we have now found that the loading of a derivatised polysaccharide with a water-soluble therapeutically active ionic material from a highly aqueous medium can be improved, with in some cases a loading of over 50%w/w being achieved from 100% aqueous solutions with the absence of irreversible gelling. The subsequent processability of a loaded fibre, tow or yarn is also simultaneously improved.

Thus, according to a first aspect of the present invention, there is provided a process for producing a medical device component comprising a derivatised polysaccharide as hereinbefore defined with a loading of a water-soluble therapeutically active ionic material, which comprises treating the derivatised polysaccharide with a highly aqueous medium comprising a water-soluble therapeutically active ionic material.

The gel product of this process of the present invention is has the property of reversible gelling on being dehydrated (for example by contact with a water- miscible or -soluble fluid medium, such as washing with an alcohol, normally ethanol), and the dehydrated product is readily processable to an absorbent device component. The present process thus avoids the disadvantage of the known similarly loaded partially carboxymethylated polysaccharides.

This process is capable of providing higher levels of loading of a therapeutically active ionic material in a derivatised polysaccharide than hitherto. A relatively high loading of a water-soluble therapeutically active ionic material from a highly aqueous medium into a derivatised polysaccharide can be achieved, and with good subsequent processability. In some cases a loading of over 50%w/w can be achieved from 100% aqueous solutions.

The process is also a less expensive process than the disadvantageous prior art processes.

The water-soluble therapeutically active ionic material with which the derivatised polysaccharide is treated may suitably be an anti-microbial salt, preferably one in which the therapeutically active material is present as a cation, for example polyhexanide (polyhexamethylene biguanide, or PHMB), in general used as its hydrochloride salt, or polyaminopropyl biguanide, PAPB, salts. The derivatised polysaccharide is treated in a highly aqueous medium, as hereinbefore defined, that is, the medium comprises at least 50%, preferably at least 75%, and in particular 100% w/w water. A non-aqueous liquid which is a water-miscible non-solvent for the polysaccharide may be added. Typically, isopropanol or ethanol will be such a solvent.

The therapeutically active ionic material is often present at a concentration of 1 to 10 %, such as 3 to 8 %, for example 5 to 6 % w/w. The loading of the therapeutically active ionic material in the highly aqueous medium that may be achieved in the derivatised polysaccharide by treatment with the water-soluble therapeutically active ionic material increases with the percentage of water present in the highly aqueous medium. Depending on the given therapeutically active ionic material, a loading of over 25% transfer may be achieved, such over 35%, for example over 50%. The treatment may suitably be carried out at a temperature of up to 30°C, which may suitably be 5 to 25° C, for example 10 to 20° C. Absorption of the fluid comprising the therapeutically is active ionic material virtually instantaneous, but depending on the particular therapeutically active material the time for the treatment process overall may suitably be 10 to 60 min, such as 15 to 45 min. 20 to 40 min. is found to be most suitable to give a more useful substrate in an economic time.

After this treatment step, residual fluids are removed, and the loaded derivatised polysaccharide is washed with at least 2 washes in an inert liquid medium comprising a dehydrating agent, for example ethanol, to absorb at least some of the water present in the loaded polysaccharide to reverse its gelation, allowing for example, 20 to 40 min per wash. Further drying can be carried out by methods known in the art such as forced air drying, radiant heat drying etc.

The third and fifth aspects of the present invention are described further hereinafter and relate to analogous processes for the loading of a derivatised polysaccharide with a therapeutically active ionic material respectively when in a non-woven fabric, and in an absorbent device.

The above derivatised polysaccharide starting materials for the process of the first aspect of the present invention may be produced by a process which comprises contacting a polysaccharide

(a) with a base in an aqueous or non-aqueous medium, and

(b) with a solution in an aqueous or non-aqueous medium of a compound of the formula (I):

M - O - R - T (I)

wherein

M is a Group IA metal cation;

O - R is a hydrocarbyl oxoacid anion; and

T is a nucleophilic leaving group; and

(c) isolating, washing and drying the product of materials (a) and (b), preferably all at a temperature below 50°C.

M may suitably be a sodium or potassium cation, preferably a sodium cation.

O - R may suitably be a hydrocarbyl acylate of an organic or inorganic oxoacid, for example an alkane acylate of an organic or inorganic oxoacid. O - R may thus suitably be, for example, an alkanoate, preferably a lower alkanoate with 2 to 6 carbon atoms, such as an acetate, glyoxylate, propionate, pyruvate or butyrate, preferably acetate, propionate or butyrate preferably attached in the 2-position to the polysaccharide oxy group.

The alkanoate moiety may be branched or unbranched, and hence suitable butyrates may be n-butyrate or iso-butyrate. The alkanoate group that is most preferred is acetate. O - R may also suitably be, for example an alkanesulphonate, preferably a lower alkanesulphonate with 2 to 6 carbon atoms, such as a methanesulphonate, ethanesulphonate, or propanesulphonate, preferably attached in the 1 -position to the polysaccharide oxy group, and more preferably methanesulphonate. The alkane moiety may be branched or unbranched, and hence suitable propane sulphonates may be propane-1 - or 2- sulphonate, and butanesulphonates may be butane-1 -sulphonate, 2, 2-dimethylethane-1 -sulphonate or 1 ,2-dimethyl- ethane-1 -sulphonate. The alkane sulphonate substituent group that is most preferred is methane sulphonate. O - R may also suitably be an arenecarboxylate, such as a benzoate or toluate, substituted by a nucleophilic leaving group T.

O - R may also suitably be an arenesulphonate, such as benzenesulphonate or toluenesulphonate, substituted by a nucleophilic leaving group T.

Suitable and preferred nucleophilic leaving groups T, when O - R is an arenecarboxylate or an arenesulphonate, and suitable and preferred substitution positions for T will be well-known to the skilled person. As noted above, the derivatised polysaccharide which is the product of steps (a) to (c) above is believed to be one in which one or both of the hydroxyl groups on the D-glucosamine units of the polysaccharide are converted at least in part to salified O - R - O - groups (etherification), where O - R is a hydrocarbyl oxoacid anion. In process steps (a) and (b), carried out at a temperature below 50°C, the base is preferably an alkali metal hydroxide, in which case the metal cation is preferably the same as M in the compound of formula (I), preferably an alkali metal hydroxide, such as sodium hydroxide.

These hydroxyl functions are preferably converted to M - O - R - O - groups; and the other hydroxyl groups on the D-glucosamine units of the polysaccharide are generally converted to hydroxyl group derivatised by the base (alkalisation), preferably M - O - groups. Either substitution may take place at either hydroxyl position.

The polysaccharide starting material may be used in the treatment process in the form of spun fibre, tow or yarn that has been suitably derivatised. The fibres may be used in a wide range of lengths, for example a few mm, such as 2mm to 5mm, to several tens of mm, for 100mm or more.

As defined herein, the derivatised polysaccharide starting material for the process is a partially organic or inorganic acylhydrocarbyl substituted polysaccharide, which is a polysaccharide in which one or more of the hydroxyl groups on the monosaccharide or aminomonosaccharide units of the polysaccharide are converted at least in part to HO - R - O - groups (etherification), where HO - R is a hydrocarbyl oxoacid residue, optionally salified preferably with an alkali metal cation. The other hydroxyl groups on the units of the polysaccharide are often present as hydroxyl group derivatised by base (alkalisation), often with the same alkali metal cation as in any salified HO - R groups that may be present. Either substitution may take place at any hydroxyl position in the polysaccharide, in any distribution up to the maximum degree of substitution that is possible.

In the derivatised polysaccharide, the degree of substitution of the hydroxyl groups in all positions by M/H - O - R - O - groups is suitably less than 0.8, preferably less than 0.7, more preferably less than 0.6 for the derivatised polysaccharide to be substantially water-insoluble. The average degree of substitution in the derivatised polysaccharide polymer may preferably be from about 0.1 to about 0.4, for example from about 0.15 to about 0.35, such as from about 0.2 to 0.3. It will be clearly appreciated by those skilled in the art that the composition, form and properties of the polysaccharide starting material of steps (a) to (c) of the process may have a significant effect on the composition, form and properties of the a derivatised polysaccharide product. In the case of a chitosan this will include the degree of deacetylation of the chitin starting material that is reached in its production, and its molecular weight. The degree of deacetylation is often from 60 to 100 %, and the average molecular weight is often between 3800 to 20,000 daltons. In the case of a cellulose, the average molecular weight is often between 3800 to 20,000 daltons.

The polysaccharide starting material may be used in the process in the form of spun chitosan fibre, tow or yarn. The fibres may be used in a wide range of lengths, for example a few mm, such as 2mm to 5mm, to several tens of mm, for 100mm or more.

In a second aspect, the present invention provides a derivatised polysaccharide loaded with a water-soluble therapeutically active ionic material, produced by the process according to the first aspect of the present invention.

The specific composition, form and properties of the product will often be determined by the specific form of the starting material of the process of the first aspect of the present invention.

The derivatised polysaccharide starting material may be used in the treatment process in the form of spun fibre, tow or yarn that has been suitably derivatised. The fibres may be used in a wide range of lengths, for example a few mm, such as 2mm to 5mm, to several tens of mm, for 100mm or more. The derivatised polysaccharides loaded with a water-soluble therapeutically active ionic materials of the invention ('loaded polysaccharides') are highly advantageous. Whilst they swell in contact with water in the highly aqueous media of the loading process to become elastic gel materials, they exhibit good reversibility of the gelation on drying. The aqueous absorbency of the dried product is good enough for it to be used as an absorbent component, for example in wound dressings. The fact that the process can be carried out without irreversible gelation occurring in a highly aqueous medium is advantageous for reasons of cost, and because the process is low- to non-toxic.

As noted above, the loaded polysaccharides of the present invention are often in the form of fibres. These meet the criteria for adequate absorbency of fluids in absorbent devices, and in particular in advanced wound dressings, and may have an absorbency of 8 to 20 grams per gram (g/g) of saline solution, often 12 to 17 g/g, and more often 13 to 16 g/g.

The derivatised polysaccharide loaded with a water-soluble therapeutically active ionic materials of the present invention may be processed according to known methods into a wide variety of forms, for example a non-woven fabric component of an absorbent device, which may suitably be of 30 to 200g/m² or more, by conventional fibre opening, web formation and needling

The loaded derivatised polysaccharide is absorbent and is often processed into and comprised in a non-woven fabric, often in an absorbent device. However, the main role of the loaded derivatised polysaccharide is to act as a reservoir of the water-soluble therapeutically active ionic material, rather than to take up fluid, and the absorbency of the loaded derivatised polysaccharide thus does not have to be at superabsorbent levels. The loaded derivatised polysaccharide in the form of fibres is therefore often processed into an absorbent fabric with other component fibres with greater absorbency, for example superabsorbency, for example fibres of the corresponding unloaded derivatised polysaccharide.

Loaded derivatised polysaccharide fibres according to the present invention may have a monofilament linear density of 0.1 to 30, preferably about 0.5 to 20, and more preferably 0.9 to 8, for example 1 3 to 5 decitex, and a strength of 0.8 to 2.2, such as 1 to 2, for example 1 .2 to 1 .8 cN/dtex. The dry strength of the loaded derivatised fibres is sufficient to enable processing into woven or preferably non-woven structures, and the wet strength of the material is sufficient, to be useful as an absorbent material in an absorbent device, in particular a wound dressing, either alone or with, for example corresponding unloaded derivatised polysaccharide. Wound dressings containing these materials absorb to a good level, even at low pH. The absorbent properties, biodegradability and renewability of the loaded derivatised polysaccharide of the present invention mean that they may be used in a wide range of absorbent devices.

A third aspect of the present invention thus provides an absorbent non-woven fabric comprising derivatised polysaccharide fibres of the second aspect of the invention loaded with a water-soluble therapeutically active ionic material.

As noted above, in may embodiments of non-woven fabrics comprising the water-insoluble loaded derivatised polysaccharide according to the invention, for example for absorbent devices, other materials are present. Such embodiments may contain other absorbent materials, such as anion-exchange resins, or hydrogels or their anhydrous precursors, for example a derivatised polysaccharide, in particular corresponding unloaded derivatised polysaccharide fibres, often in the form of fibres which are intermingled with the loaded derivatised polysaccharide according to the invention. The overall absorptive capacity of the fabric is sensitive to the sizes and interconnectivity of the inter-fibre volumes within it, and hence to the parameters of the process for its manufacture, and will often differ from that of the component fibres. It is also sensitive to the absorbency of its absorbent components. Thus, preferably, the other absorbent materials in the fabric have an absorbency of 8 to 30 grams per gram (g/g) of saline solution, often 12 to 27 g/g, and more often 16 to 23 g/g.

The addition of unloaded polysaccharide to the loaded derivatised polysaccharide may have a significant improving effect on the absorbency of the non-woven material. The overall absorbency of absorbent non-woven fabrics of the present invention comprising a loaded derivatised polysaccharide and at least one other absorbent material is preferably from 8 to 25 grams per gram (g/g) of saline solution, often 12 to 22 g/g, and more often 13 to 21 g/g, especially meeting the criteria for adequate absorbency in advanced wound dressings.

Preferably, such materials are added after drying. For example, unloaded derivatised polysaccharide fibre may be added, in a weight ratio of derivatised polysaccharide fibre to the loaded derivatised polysaccharide fibre of 1 :9 to 9:1 , for example of 1 :6 to 6:1 or 1 :3 to 3:1 .

The blend of loaded and unloaded derivatised polysaccharide may be processed according to known methods into a wide variety of forms, for example a non- woven fabric component of an absorbent device, which may suitably be of 30 to 200g/m² or more, by conventional fibre opening, web formation and needling

In other, less preferred embodiments of non-woven fabrics comprising the water- insoluble loaded derivatised polysaccharide loaded according to the invention, for example for absorbent devices, it is the only absorbent material present.

Both embodiments may comprise relatively non-absorbent, for example strengthening polymeric materials, also often in the form of fibres which are intermingled with the loaded derivatised polysaccharide according to the invention.

Thus, another embodiment of the present invention is directed to a non-woven fabric comprising a water-insoluble derivatised polysaccharide loaded with a water-soluble therapeutically active ionic material of the present invention which is reinforced with a reinforcing fibre blended with the derivatised polysaccharide loaded with a water-soluble therapeutically active ionic material.

Examples of reinforcing materials that may be present include relatively non- absorbent, for example polymeric, strengthening materials, such as unmodified polysaccharide or thermoplastic bicomponent fibres, most preferably having a polyolefin component, for example comprising a polyolefin-containing polymeric material of which the largest part (by weight) consists of homo- or copolymers of monoolefins such as ethylene, propylene, 1 -butene, 4-methyl-l-pentene, etc. Preferably, such materials are added after drying. For example, un-modified polysaccharide fibre may be added, in a weight ratio of polysaccharide fibre to the derivatised polysaccharide loaded with a water-soluble therapeutically active ionic material fibre of 1 :9 to 9:1 , for example of 1 :3 to 3:1 . The blend of loaded derivatised polysaccharide and reinforcing materials may be processed according to known methods into a wide variety of forms, for example a non- woven fabric component of an absorbent device, which may suitably be of 30 to 200g/m² or more, by conventional fibre opening, web formation and needling Preferred fabrics comprising a loaded derivatised polysaccharide for use in wound care medical devices are carded, needle-bonded non-wovens.

The addition of reinforcing fibres to the loaded derivatised polysaccharide may have a significant improving effect on the strength of the non-woven material.

The absorbent non-woven fabric of the third aspect of the present invention may also be provided by an alternative process for its manufacture. This alternative process forms a fourth aspect of the present invention, and is a variant of the process according to the first aspect of the present invention for producing a derivatised polysaccharide loaded with a water-soluble therapeutically active ionic material. In this alternative process, the derivatised polysaccharide starting material of the process of the first aspect of the invention is processed according to known methods, as described above, into a non-woven fabric, and the alternative process comprises treating the derivatised polysaccharide, comprised in a non- woven fabric, with a highly aqueous medium comprising a water-soluble therapeutically active ionic material.

Suitable water-soluble therapeutically active ionic material with which the derivatised polysaccharide is treated may suitably be an anti-microbial, for example polyhexanide (polyhexamethylene biguanide, or PHMB), in general used as its hydrochloride salt, or polyaminopropyl biguanide, PAPB, salts. The derivatised polysaccharide is treated in a highly aqueous medium, as hereinbefore defined, that is, the medium comprises at least 50%, preferably at least 75%, and in particular 100% w/w water. A non-aqueous liquid which is a water-miscible non-solvent for the polysaccharide may be added. Typically, isopropanol or ethanol will be such a solvent.

The therapeutically active ionic material is often present at a concentration of 1 to 10 %, such as 3 to 8 %, for example 5 to 6 % w/w. The loading of the therapeutically active ionic material in the highly aqueous medium that may be achieved in the derivatised polysaccharide by treatment with the water-soluble therapeutically active ionic material increases with the percentage of water present in the highly aqueous medium. Depending on the given therapeutically active ionic material, a loading of over 25% transfer may be achieved, such over 35%, for example over 50%.

Conditions for the treatment, such as treatment temperature and time are similar to those described further hereinbefore in respect of the process of the first aspect of the present invention for the loading of a derivatised polysaccharide. As noted above, the loaded polysaccharides of the present invention, often in the form of fibres, meet the criteria for adequate absorbency of fluids in absorbent devices, and in particular in advanced wound dressings, and may have an absorbency of 8 to 20 grams per gram (g/g) of saline solution, often 12 to 17 g/g, and more often 13 to 16 g/g. However, the absorbency of the loaded derivatised polysaccharide is not at superabsorbent levels, as may be required in absorbent devices, and in particular in advanced wound dressings.

The non-woven fabrics comprising the loaded derivatised polysaccharide may be required to have an absorbency of 8 to 25 grams per gram (g/g) of saline solution, often 12 to 22 g/g, and more often 13 to 21 g/g, especially meeting the criteria for adequate absorbency in advanced wound dressings.

The loaded derivatised polysaccharide in the form of fibres are therefore often processed into an absorbent fabric with other component fibres with greater absorbency, for example superabsorbency, which absorbency is not sensitive to the treatment process. Thus, preferably, the other absorbent materials in the fabric have an absorbency of 8 to 30 grams per gram (g/g) of saline solution, often 12 to 27 g/g, and more often 16 to 23 g/g, after undergoing the treatment process. Examples include anion-exchange resins, or hydrogels or their anhydrous precursors, for example a derivatised polysaccharide (but not generally corresponding unloaded derivatised polysaccharide fibres), often in the form of fibres which are intermingled with the loaded derivatised polysaccharide according to the invention. The addition of unloaded polysaccharide to the loaded derivatised polysaccharide may have a significant improving effect on the absorbency of the non-woven material. Preferably, such materials are added to the loaded derivatised polysaccharide fibre after drying of the latter, and the blend processed conventionally to a non-woven fabric.

As noted above, in other non-woven fabrics which are the process starting materials, other materials may be present, such as reinforcing fibrous materials.

The starting material non-woven fabric (including any additive materials as above) may be prepared from unloaded derivatised polysaccharide fibre by fibre opening, web formation and needling, which may suitably give rise to a non- woven of 30 to 200g/m² or more.

The therapeutically active, absorbent non-woven fabrics produced by the process of the fourth aspect of the present invention also meet the criteria for good absorbency of fluids required for medical absorbent devices.

The non-woven fabric (prepared by either of the above routes) may then be converted to an anti-microbial absorptive component of a non-woven absorptive device by cutting, packaging and sterilising.

In a fifth aspect of the present invention there is provided an absorbent device (as defined hereinbefore) comprising a derivatised polysaccharide loaded with a water-soluble therapeutically active ionic material fibres of the second aspect of the invention. Their absorbent properties, biodegradability and renewability mean that the loaded derivatised polysaccharides of the present invention may be used in a wide range of absorbent devices. The absorbent materials of the present invention exhibit virtually instantaneous gelling in aqueous media, good absorbency and, crucially, good retention of absorbency in an acidic environment. Whilst they swell in contact with water to become an elastic gel material, and exhibit good absorption and retention of fluid, they maintaining their integrity sufficiently, for example in wound dressings, to be removed from the wound site in one piece, without irrigation, and with minimum pain and shedding.

When fully hydrated, such a component of an absorbent medical device is substantially transparent. This is advantageous in wound care applications since the state of the underlying wound can be determined without removing the dressing. This renders them ideal for use as an absorbent wound care product, such as a dressing, or as part of an absorbent wound care product. They are suited for use in wound dressings for acute wounds, including surgical wounds, and chronic and burn wounds. They are particularly useful for wounds with moderate to high levels of exudates, and for flat or cavity wounds of this type. Typical examples include burn wounds, and chronic wounds, such as pressure sores and leg ulcers. The dressing, when covering a wound, is able to prevent water in body fluids from being lost, providing a favourable moist environment for wound healing and maintaining a fluid-free, maceration-free, germ-free wound surface.

They may also be used in ostomy devices, and surgical and dental sponges.

Thus, one embodiment of this fifth aspect of the present invention provides an absorbent medical device comprising the loaded derivatised polysaccharide of the first aspect of the invention, such as a wound dressing.

Such wound dressings will often comprise a non-woven fabric comprising a loaded derivatised polysaccharide of the third aspect of the invention.

The use of the absorbent materials of the present invention is not limited to medical products, however, and they are useful for other applications. Their absorbent properties, biodegradability and renewability also mean that the loaded derivatised polysaccharide materials of the invention are particularly desirable for use in absorbent pads for the personal care sector, particularly for disposable sanitary devices such as nappies (diapers), disposable nappies and training pants, feminine care products, for example, tampons, sanitary towels, or napkins and pant liners, and incontinence products. .

Thus, another embodiment of this fifth aspect of the present invention provides an absorbent personal care device comprising a loaded derivatised polysaccharide of the second aspect of the invention.

Suitable and preferred non-woven fabrics comprising the loaded derivatised polysaccharide are as so described hereinbefore.

For example they may be required to have an absorbency of 8 to 25 grams per gram (g/g) of saline solution, often 12 to 22 g/g, and more often 13 to 21 g/g, especially meeting the criteria for adequate absorbency in advanced wound dressings.

The loaded derivatised polysaccharide in the form of fibres are therefore often processed into an absorbent fabric with other component fibres with greater absorbency, for example superabsorbency, which absorbency is not sensitive to the treatment process. Thus, preferably, the other absorbent materials in the fabric have an absorbency of 8 to 30 grams per gram (g/g) of saline solution, often 12 to 27 g/g, and more often 16 to 23 g/g, after undergoing the treatment process. Examples include anion-exchange resins, or hydrogels or their anhydrous precursors, for example a derivatised polysaccharide (but not generally corresponding unloaded derivatised polysaccharide fibres), often in the form of fibres which are intermingled with the loaded derivatised polysaccharide according to the invention.

The addition of unloaded polysaccharide to the loaded derivatised polysaccharide may have a significant improving effect on the absorbency of the non-woven material. Such non-woven fabrics are processed conventionally to an absorptive component of an absorbent device.

The absorbent device of the fifth aspect of the present invention may also be provided by an alternative process for its manufacture, which forms a sixth aspect of the present invention, and is a variant of the process according to the first aspect of the present invention for producing a derivatised polysaccharide loaded with a water-soluble therapeutically active ionic material.

In this variant, the loaded derivatised polysaccharide of the second aspect of the invention is processed according to known methods into a non-woven fabric, which is in turn processed according to known methods into an absorbent component of an absorbent device, and the alternative process comprises treating the derivatised polysaccharide, comprised in an absorbent device, with a highly aqueous medium comprising a water-soluble therapeutically active ionic material.

Suitable water-soluble therapeutically active ionic material with which the derivatised polysaccharide is treated may suitably be an anti-microbial, for example polyhexanide (polyhexamethylene biguanide, or PHMB), in general used as its hydrochloride salt, or polyaminopropyl biguanide, PAPB, salts.

The derivatised polysaccharide is treated in a highly aqueous medium, as hereinbefore defined, that is, the medium comprises at least 50%, preferably at least 75%, and in particular 100% w/w water. A non-aqueous liquid which is a water-miscible non-solvent for the polysaccharide may be added. Typically, isopropanol or ethanol will be such a solvent.

The therapeutically active ionic material is often present at a concentration of 1 to 10 %, such as 3 to 8 %, for example 5 to 6 % w/w. The percentage of the therapeutically active ionic material in the highly aqueous medium that may be transferred to the derivatised polysaccharide in the course of the treatment with the water-soluble therapeutically active ionic material increases with the percentage of water present in the highly aqueous medium. Depending on the specific therapeutically active ionic material, over 70% transfer may be achieved, such as over 60%, for example over 50%. Conditions for the treatment, such as treatment temperature and time are similar to those described further hereinbefore in respect of the process of the first aspect of the present invention for the loading of a derivatised polysaccharide. As noted above, the loaded polysaccharides of the present invention, often in the form of fibres, meet the criteria for adequate absorbency of fluids in absorbent devices, and in particular in advanced wound dressings, and may have an absorbency of 8 to 20 grams per gram (g/g) of saline solution, often 12 to 17 g/g, and more often 13 to 16 g/g. However, the absorbency of the loaded derivatised polysaccharide is not at superabsorbent levels, as may be required in absorbent devices, and in particular in advanced wound dressings.

The loaded derivatised polysaccharide in the form of fibres are therefore often processed into an absorbent fabric with other component fibres with greater absorbency, for example superabsorbency, which absorbency is not sensitive to the treatment process, as described hereinbefore in relation to the absorbent non-woven fabric of the third aspect of the invention.

A seventh aspect of the present invention provides a method of treatment or prophylaxis which comprises applying a dressing according to the fifth aspect of the invention to a wound in a human or animal body.

The invention will now be illustrated by the following non-limiting examples.

Example 1 - Preparation of starting materials

A solution containing 10.625 kg sodium hydroxide (40% solution), 4.5 kg sodium chloroacetate (44% solution) and 100 kg ethanol (60% solution) was prepared, the remainder being deionised water. The solution was heated to 30° C. 5.0 kg polysaccharide fibres were added and the solution reacted for 45 minutes. The temperature of the solution was then increased to 40° C, and the fibres were reacted for a further 120 minutes. The modified fibres underwent 5 spin dry and ethanol wash cycles and a final spin dry. The fibres were treated with a spin finish comprised 1 .523% Tween 20 and 98.478% ethanol (95%). The fibres underwent another spin dry after fibre finish application and were left to air dry and condition.

Example 2

A 5x5 cm swatch of non-woven fabric manufactured from the material of Example 1 was immersed in 4%w/w solution of PHMB hydrochloride (20 ml) made up in 100% water and left to stand at ambient temperature (15 °C) for 30 minutes. After this time, the swatch was removed from the solution and immediately transferred to 40 ml ethanol and left to stand for a further 30 minutes. After this time, the sample was removed from the wash medium and paper toweled dry with light hand pressure then left to dry at 40 °C for 1 hour followed by air-drying at ambient temperature overnight. The product was of the same gross dimensions as the starting material but was slightly stiffer in feel.

Example 3

A 5x5 cm swatch of non-woven fabric manufactured from the material of Example 1 was immersed in 4%w/w solution of PHMB hydrochloride (20 ml) made up in 80%water-20%ethanol and left to stand at ambient temperature (15 °C) for 30 minutes. After this time, the swatch was removed from the solution and immediately transferred to 40 ml ethanol and left to stand for a further 30 minutes. After this time, the sample was removed from the wash solvent and paper toweled dry with light hand pressure then left to dry at 40 °C for 1 hour followed by air-drying at ambient temperature overnight. The product was of the same gross dimensions as the starting material but was slightly stiffer in feel. Example 4

A 5x5 cm swatch of non-woven fabric manufactured from the material of Example 1 was immersed in 4%w/w solution of PHMB hydrochloride (20 ml) made up in 60%water-40%ethanol and left to stand at ambient temperature (15 °C) for 30 minutes. After this time, the swatch was removed from the solution and immediately transferred to 40 ml ethanol and left to stand for a further 30 minutes. After this time, the sample was removed from the wash solvent and paper toweled dry with light hand pressure then left to dry at 40 °C for 1 hour followed by air-drying at ambient temperature overnight. The product was of the same gross dimensions and feel as the starting material.

Example 5

A 5x5 cm swatch of non-woven fabric manufactured from the material of Example 1 was immersed in 4%w/w solution of PHMB hydrochloride (20 ml) made up in 40%water-60%ethanol and left to stand at ambient temperature (15 °C) for 30 minutes. After this time, the swatch was removed from the solution and immediately transferred to 40 ml ethanol and left to stand for a further 30 minutes. After this time, the sample was removed from the wash solvent and paper toweled dry with light hand pressure then left to dry at 40 °C for 1 hour followed by air-drying at ambient temperature overnight. The product was of the same gross dimensions and feel as the starting material. Example 6

A 5x5 cm swatch of non-woven fabric manufactured from the material of Example 1 was immersed in 4%w/w solution of PHMB hydrochloride (20 ml) made up in 20%water-80%ethanol and left to stand at ambient temperature (15 °C) for 30 minutes. After this time, the swatch was removed from the solution and immediately transferred to 40 ml ethanol and left to stand for a further 30 minutes. After this time, the sample was removed from the wash solvent and paper toweled dry with light hand pressure then left to dry at 40 °C for 1 hour followed by air-drying at ambient temperature overnight. The product was of the same gross dimensions and feel as the starting material.

Example 7 - Quantification of PHMB loading

The samples prepared in Examples 2 - 6 were tested in the following manner:

Nitroprusside reagent solution was prepared as follows:

Deionised water (20 ml) was added by Gilson pipette to sodium nitroprusside (500 mg).

Deionised water (5 ml) was added by Gilson pipette to potassium hexacyanoferrate (500 mg).

Deionised water (5 ml) was added by Gilson pipette to sodium hydroxide (500 mg). When fully dissolved, all solutions were combined to generate an amber solution of the assay reagent which was left to stand overnight in the absence of light prior to use. The reagent solution was discarded after 4 days. Assay method:

A 2x2 cm swatch of each sample was placed into a 5x5 cm zip-loc bag. 1 ml of nitroprusside reagent was added to the sample and the gelled sample was manoeuvred into a bottom corner of the bag. The sample was minimally manipulated to eliminate air-locks. The bag was closed, minimising the trapping of air. The sample was allowed to stand for at least 30 minutes prior to analysis.

For analysis, the sample was taken in its bag and trapped between two glass microscope slides separated by a 2 mm shim. The sample was placed in the beam of a UV-vis spectrometer. A PHMB-free sample was treated likewise and placed in the reference beam (for dual-beam spectrometers). Absorbance was measured at 520 nm (an absorbance shoulder).

PHMB loading was determined with reference to a set of reference samples of known PHMB loading:

Increasing the water content of the loading solvent increased the %w/w PHMB device loading in general.

Claims

A process for producing a medical device component, comprising a derivatised polysaccharide which is a partially organic or inorganic acylhydrocarbyl substituted polysaccharide in which one or more of the hydroxyl groups on the units of the polysaccharide have been onverted at least in part to optionally salified HO - R - O - groups, where HO - R is a hydrocarbyl oxoacid residue, which comprises treating the derivatised polysaccharide with a highly aqueous medium comprising a water-soluble therapeutically active ionic material.

A process according to claim 1 wherein the derivatised polysaccharide is produced by a process which comprises contacting a polysaccharide

(a) with a base in an aqueous or non-aqueous medium, and

(b) with a solution in an aqueous or non-aqueous medium of a salt of the formula (I):

M - O - R - T (I)

wherein

M is a Group IA metal cation;

O - R is a hydrocarbyl oxoacid anion; and

T is a nucleophilic leaving group; and

(c) isolating, washing and drying the product of steps (a) and (b),

all at a temperature below 50°C.

A process according to claim 1 wherein the derivatised polysaccharide is a derivatised chitosan.

A process according to claim 1 , wherein the moiety - O - R - O is carboxymethyl anion.

A process according to claim 1 , wherein the moiety - O - R - T is sulphonylmethyl anion.

A process according to claim 1 , wherein the water-soluble therapeutically

active ionic material is a polyhexamethylene biguanide salt or a polyaminopropyl biguanide salt.

7. A process according to claim 1 , wherein the highly aqueous medium comprises at least 75% w/w water.

8. A process according to claim 1 , wherein the highly aqueous medium comprises 100% .w/w water.

9. A process according to claim 1 , wherein isopropanol and/or ethanol is present in the highly aqueous medium. 10. A process according to claim 1 , wherein the water-soluble therapeutically active ionic material is present at a concentration of 5 to 6 % w/w.

1 1 . A derivatised polysaccharide which is a partially organic or inorganic acylhydrocarbyl substituted polysaccharide in which one or more of the hydroxyl groups on the units of the polysaccharide have been converted at least in part to optionally salified HO - R - O - groups, where HO - R is a hydrocarbyl oxoacid residue, loaded with a water-soluble therapeutically active ionic material. 12. An absorbent non-woven fabric comprising a loaded derivatised polysaccharide according to claim 1 1 .

13. A process for preparing a non-woven fabric according to claim 12, which comprises treating a non-woven fabric comprising an acylhydrocarbyl substituted polysaccharide in which one or more of the hydroxyl groups on the units of the polysaccharide have been converted at least in part to optionally salified HO - R - O - groups, where HO - R is a hydrocarbyl oxoacid residue, with a highly aqueous medium comprising a water-soluble therapeutically active ionic material.

14. An absorbent device comprising a further derivatised polysaccharide according to claim 1 1 .

15. An absorbent device according to claim 14 which is a wound dressing.

16. A process for preparing an absorbent device according to claim 12, which comprises reacting an absorbent device comprising a derivatised polysaccharide in which one or more of the hydroxyl groups on the units of the polysaccharide have been converted at least in part to optionally salified HO - R - O - groups, where HO - R is a hydrocarbyl oxoacid residue, with a highly aqueous medium comprising a water-soluble therapeutically active ionic material.

17. A method of treatment or prophylaxis which comprises applying a dressing according to claim 15 to a wound in a human or animal body.