WOUND DRESSING FOR TREATMENT OF DAMAGED SKIN

Abstract

Adhesive wound dressing that comprises an absorbent matrix (A) adhering to the central portion of a polyurethane backing (B) having an adhesive layer for the skin, said matrix (A) comprising: a. a breathable and porous polyethylene film at the end designed to come into contact with the wound; b. an absorbent layer made of non-woven fabric adjacent to film a), said absorbent layer consisting of: i. 60-65% viscose ii. 25-30% polyester iii. 5-15% polypropylene; c. a layer of polyethylene inserted between layer b) and a layer d. of hydrophobic polystyrene, the latter being in contact with the central portion of polyurethane backing (B); wherein matrix (A) is impregnated with a solution of one or more polysaccharides or the salts thereof.

Claims

1. Adhesive wound dressing which comprises an absorbent matrix (A) adhering to a central portion of a polyurethane backing (B) having an adhesive layer for the skin, said matrix (A) comprising: a. a breathable and porous polyethylene film at the end designed to come into contact with the wound; b. an absorbent non-woven fabric layer adjacent to film a), said absorbent layer consisting of: i. 60-65% viscose ii. 25-30% polyester iii. 5-15% polypropylene; c. an adhesive polyethylene layer inserted between layer b) and a layer d. of hydrophobic polystyrene, the latter being in contact with the central portion of polyurethane backing (B); wherein matrix (A) is impregnated with a solution of one or more polysaccharides, or salts or derivatives thereof.

2. Wound dressing according to claim 1 wherein the adhesive layer of backing (B) is a layer of polyacrylic glue.

3. Wound dressing according to claim 1 wherein absorbent layer b) consists of: i. 60% viscose; ii. 25% polyester; iii. 15% polypropylene.

4. Wound dressing according to claim 1 wherein the polysaccharide is selected from glycosaminoglycans, chitin, chitosan, pectin, pectinic acid, galactans, alginic acid and alginates, glucans, natural gums, fructans, polymannans, carrageenan and derivatives of said polysaccharides.

5. Wound dressing according to claim 4 wherein the polysaccharide is hyaluronic acid sodium salt or a derivative thereof with an average molecular weight ranging from 400 to 3×10.sup.6Da.

6. Wound dressing according to claim 1 wherein the concentration of the polysaccharide ranges from 0.1% to 1% w/w.

7. Wound dressing according to claim 5 wherein the hyaluronic acid sodium salt has an average molecular weight ranging from 150,000 to 250,000 Da and is present in the concentration of 0.3% w/w.

8. Wound dressing according to claim 1 wherein the polysaccharide is a hyaluronic acid derivative selected from esters, amides, inner esters, O-sulfated derivatives and percarboxylated derivatives.

9. Wound dressing according to claim 8 wherein the hyaluronic acid derivative is the grade 3 O-sulfated derivative at a concentration ranging from 0.1% to 1% w/w.

10. Wound dressing according to claim 1 wherein matrix (A) has an average thickness ranging from 2.5 (±0.3) to 3.0 (±0.3) mm.

11. Wound dressing according to claim 10 wherein matrix (A) is impregnated to 50% of its maximum absorption capacity by homogeneous spraying of 65±5 mg/cm.sup.2 of the solution containing the polysaccharide, preferably hyaluronic acid sodium salt or a derivative thereof.

12. Wound dressing according to claim 11 wherein the polysaccharide is hyaluronic acid sodium salt and matrix (A) has an average thickness of 2.7±0.3 mm and an absorption power≥20 g/100 cm.sup.2 in a time≤1 sec.

13. Wound dressing according to claim 1 wherein absorbent layer b) consists of 60% viscose, 25% polyester and 15% polypropylene, matrix (A) has an average thickness of 2.7±0.3 mm and an absorbent power≥20 g/100 cm.sup.2 in a time of ≤1 sec, and is impregnated to 50% of its maximum absorption capacity by homogeneous spraying of 65±5 mg/cm.sup.2 of a solution of hyaluronic acid sodium salt with an average molecular weight ranging between 150,000 and 250,000 Da at the concentration of 0.3% w/w.

14. Wound dressing according to claim 1 wherein matrix (A) contains pharmacologically/biologically active substances selected from iodine, silver sulfadiazine, metallic, colloidal or micronised silver, antibiotics for topical use, local anaesthetics, NSAIDs, steroids for topical use, cytostatics, growth factors, fibrinolytics and antioedema agents, proteolytic enzymes, collagenase, hyaluronidase, anticoagulants, proteins such as collagen or silk proteins such as fibroin, Triticum vulgare extract and absorbent polymers.

15. Wound dressing according to claim 1 for surgical use in the treatment of wounds, burns, ulcers of various kinds, abrasions, and slight or moderate grazes.

16. Wound dressing according to claim 1 for dermatological use in the treatment of local inflammations that may cause skin lesions or microlesions.

17. Wound dressing according to claim 1 for dermocosmetic use in the treatment of skin relaxation with or without lesions or microlesions.

18. Wound dressing according to claim 2 wherein absorbent layer b) consists of: i. 60% viscose; ii. 25% polyester; iii. 15% polypropylene.

19. Wound dressing according to claim 2 wherein the polysaccharide is selected from glycosaminoglycans, chitin, chitosan, pectin, pectinic acid, galactans, alginic acid and alginates, glucans, natural gums, fructans, polymannans, carrageenan and derivatives of said polysaccharides.

20. Wound dressing according to claim 3 wherein the polysaccharide is selected from glycosaminoglycans, chitin, chitosan, pectin, pectinic acid, galactans, alginic acid and alginates, glucans, natural gums, fructans, polymannans, carrageenan and derivatives of said polysaccharides.

Description

DESCRIPTION OF THE INVENTION

[0024] The object of the present invention is an adhesive wound dressing that combines the characteristics of advanced wound dressings, as defined above, with the characteristics and benefits of a biomaterial, thus avoiding the need for a secondary dressing due to its adhesive capacity, which is not currently found in any of the biomaterials used for wound healing.

[0025] The wound dressing of the invention preferably comprises, as active agent, hyaluronic acid (HA) sodium salt or a derivative thereof having a specific average molecular weight (MW), which creates the optimum conditions for migration of the fibroblasts from the edges to the centre of the wound, thus stimulating their proliferation, accelerates the macrophagic response (the presence of macrophages is essential for correct wound healing), and performs its well-known hydrating, anti-inflammatory and painkilling activity.

[0026] The wound dressing of the invention comprises an absorbent matrix (A) adhering to the central portion of a polyurethane backing (B) having an adhesive layer for the skin, said matrix (A) comprising: [0027] a. a breathable, porous polyethylene film, the surface whereof is intended to come into contact with the wound, wherein said film does not adhere to the wound; [0028] b. an absorbent layer made of non-woven fabric adjacent to film a), said absorbent layer consisting of: [0029] i. 60-65% viscose [0030] ii. 25-30% polyester [0031] iii. 5-15% polypropylene; [0032] c. a layer of adhesive polyethylene inserted between layer b) and a layer [0033] d. of hydrophobic polystyrene, the latter being in contact with the central portion of polyurethane backing (B),

[0034] wherein matrix (A) is impregnated with a solution of one or more optionally salified polysaccharides.

[0035] Due to its particular structure and materials, the wound dressing of the invention is permeable to water vapour and easy to remove without skin trauma, and has a strong, transparent, waterproof backing (B).

[0036] The wound dressing of the invention has the following properties: [0037] it ensures the maintenance of a moist microenvironment at the wound-dressing interface (for as long as it remains in contact with the wound), stimulating fibroblast proliferation and therefore correct, rapid wound healing, [0038] it prevents adherence between new granulation tissue and the matrix placed in direct contact with the wound (if the adherence is not kept moist, it may give rise to a “dry” eschar that traps the new granulation tissue), [0039] it only adheres to the undamaged part surrounding the damaged tissue, and is easy to remove without trauma, [0040] it promotes and guarantees: [0041] thermal insulation of the damaged skin, ensuring correct breathability, [0042] absorption of excess exudate, [0043] pain control, [0044] protection against exogenous infections, [0045] greater comfort for the patient, as fewer dressing changes are required than with the currently known dressings.

[0046] Due to its specific conformation and the presence of the polysaccharide, the wound dressing of the invention actively promotes correct skin regeneration, facilitates a rapid wound-healing process, protects the wound against microbial contamination, controls pain and prevents the formation of hypertrophic scars. The wound dressing therefore has all the characteristics of a biomaterial, and does not require a secondary dressing.

[0047] The polysaccharides that can be used for the purposes of the invention comprise glycosaminoglycans, chitin, chitosan, pectin, pectinic acid, galactans, alginic acid and alginates, glucans, natural gums, fructans, polymannans, carrageenan and derivatives of said polysaccharides.

[0048] Examples of glycosaminoglycans include hyaluronic acid and/or derivatives thereof such as salts, esters, amides and sulfated hyaluronic acid; hybrid complexes of high- and low-molecular-weight hyaluronic acid (described in WO2012/032151); chondroitin, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparan sulfate, heparin and heparinoids.

[0049] An example of a chitosan derivative is chitosan derivatised with lactose (described in WO2007/135116 and WO2017/211776).

[0050] Examples of galactans include agar and agarose. Examples of glucans include dextran, dextrin, trehalose, maltose, starch, cellulose and derivatives thereof, preferably hydroxyethylcellulose, carboxymethylcellulose, hydroxymethylcellulose and cellulose acetate.

[0051] Examples of natural gums include gellan gum and xanthan gum. A preferred fructan is inulin.

[0052] A preferred polysaccharide is hyaluronic acid sodium salt or derivatives thereof prepared from hyaluronic acid obtained from any source, for example by extraction from rooster combs (EP138572), by fermentation (from Streptococcus equi or zooepidemicus, EP716688), or by biosynthesis (from Bacillus, EP2614088). The average molecular weight ranges between 400 and 3×10.sup.6Da, in particular between 1×10.sup.5Da and 1×10.sup.6Da, even more particularly between 150,000 and 250,000 Da and/or between 500,000 and 1×10.sup.6Da.

[0053] The most preferred polysaccharides are hyaluronic acid sodium salt with an average molecular weight ranging between 150 and 250 kDa, hybrid complexes of low- and high-molecular-weight hyaluronic acids wherein the high-molecular-weight hyaluronic acid ranges between 1100 and 1400 kDa and the low-molecular-weight hyaluronic acid ranges between 80 and 100 kDa, and chitosan derivatized with lactose.

[0054] “Average molecular weight” (MW) here means the weight-average MW, calculated by the “intrinsic viscosity” method (Terbojevich et al., Carbohydr Res, 1986, 363-377).

[0055] The HA derivatives that can be used to form the matrix of the wound dressing of the invention comprise:

[0056] HYAFF®: HA esters with alcohols of the aliphatic, arylaliphatic, cycloaliphatic, aromatic, cyclic and heterocyclic series, preferably benzyl ester with an esterification percentage preferably ranging between 1 and 50%, while the remaining percentage of non-esterified HA can be salified with sodium (EP216453);

[0057] HYADD®: HA amides with amines of the aliphatic, arylaliphatic, cycloaliphatic, aromatic, cyclic and heterocyclic series, preferably HA hexadecyl amide with an amidation percentage ranging between 0.1 and 5%, while the remaining percentage of non-amidated HA can be salified with sodium (EP1095064);

[0058] O-sulfated derivatives of HA up to the 4th degree of sulfation, preferably grade 1 or grade 3 (EP702699, WO2017085622);

[0059] ACP®: inner esters of HA with an esterification percentage ranging between 0.05 and 5%, while the remaining percentage of non-esterified HA can be salified with sodium (EP341745);

[0060] HYOXX™: percarboxylated derivatives of HA obtained by oxidation of the primary hydroxyl of the N-acetyl-glucosamine fraction with a degree of percarboxylation ranging between 0.1 and 100%, preferably between 2 and 5%. All the carboxyl groups of HA can be salified with sodium (EP1339753).

[0061] The adhesive layer of polyurethane backing (B) (last outer layer) is preferably a layer of polyacrylic glue; said layer ensures both adherence to the matrix and adherence to the skin in the areas surrounding matrix (A).

[0062] Matrix (A), characterised by a high absorption capacity, is moist because it is impregnated with an aqueous solution comprising a polysaccharide as active agent, preferably hyaluronic acid sodium salt (NaHA) or a derivative thereof, combined with suitable excipients; the concentration of the polysaccharide or the HA salt or HA derivative ranges between 0.1% and 1% w/w, preferably between 0.2% and 0.6% w/w. The solution can also include other ingredients such as solvents, preservatives and pH correctors. Examples of said ingredients include glycerol, propylene glycol, 2-phenylethanol, ethylhexylglycerin, lactic acid and other excipients suitable for topical application.

[0063] The preferred active agent is hyaluronic acid sodium salt, NaHA, prepared from an HA produced by fermentation from Streptococcus, at a concentration ranging between 0.1% and 1% w/w and preferably between 0.2% and 0.6% w/w, with an average MW preferably ranging between 150,000 and 250,000 Da and/or between 500,000 and 1×10.sup.6 Da, or a derivative thereof, preferably grade 3 O-sulfated hyaluronic acid, HAS; NaHA with an average MW ranging between 150,000 and 250,000 Da at the concentration of 0.3% w/w is most preferred as active agent.

[0064] An example of a solution which can be used according to the invention for absorption on matrix (A) has the composition shown in Table A:

TABLE-US-00001 TABLE A Active agent: Quantity: g/100 g NaHA or its derivative 0.1-1.0 Excipients Glycerol 20-30 1,3-propanediol (propylene glycol) 2-6 Lactic acid 0.0002-0.0006 q.s. to pH 5.5 2-phenylethanol 0.4-0.8 Ethylhexylglycerin 0.04-0.08 Purified water q.s. to 100 g

[0065] The solutions can optionally contain additional pharmacologically/biologically active plant-based or synthetic substances. Examples of pharmacologically/biologically active substances include medicaments for topical use such as NSAIDs and steroids; antibacterials/antibiotics, preferably iodine, silver sulfadiazine or metallic silver; cytostatics; growth factors; fibrinolytics and antioedema agents; proteolytic enzymes, preferably collagenase, hyaluronidase; anticoagulants; proteins such as collagen or silk proteins such as fibroin; local anaesthetics such as lidocaine; Triticum vulgare extract; and absorbent polymers such as CMC. The matrix of the wound dressing of the invention is impregnated to 50% of its maximum absorption capacity by homogeneous spraying of the aqueous solution containing the active agent, such as the solution described in Table A; said matrix is then impregnated with 65±5 mg/cm.sup.2. A matrix with a size of 25 cm.sup.2 therefore contains 1.67 g of said liquid composition.

[0066] The matrix typically has an average thickness of 2.5 (±0.3) to 3.0 (±0.3) mm, preferably 2.7±0.3 mm, with an absorbent power (of liquids)≥20 g/100 cm.sup.2 in a time of ≤1 sec.

[0067] The preferred composition of the absorbent layer of non-woven fabric is 60% viscose, 25% polyester and 15% polypropylene (percentages by weight).

[0068] A particularly preferred solution which can be used according to the invention to be absorbed on the absorbent layer of 60% viscose, 25% polyester and 15% polypropylene has the composition shown in Table B:

TABLE-US-00002 TABLE B Active agent: Quantity: g/100 g NaHA with an average MW ranging 0.3 between 150,000 and 250,000 Da Excipients Glycerol 25 1,3-propanediol (propylene glycol) 4 Lactic acid 0.0005 q.s. to pH 5.5 2-phenylethanol 0.54 Ethylhexylglycerin 0.06 Purified water q.s. 100 g

[0069] Matrix (A) which, in its preferred form, adheres to the adhesive polyurethane backing with polyacrylic glue, possesses an average thickness of 2.7±0.3 mm and an absorbent power≥20 g/100 cm.sup.2 in a time of ≤1 sec, and is impregnated to 50% of its maximum absorption capacity by homogeneous spraying of 65±5 mg/cm.sup.2 of the liquid pharmaceutical composition described in Table B.

[0070] The wound dressings of the invention are useful for surgical use in the treatment of wounds, burns, ulcers of different origin, slight or moderate abrasions, and all skin lesions requiring the use of an advanced dressing.

[0071] The wound dressings of the invention are also useful for dermatological use in the treatment of local inflammations which can cause skin lesions or microlesions such as psoriasis, various forms of inflammatory dermatitis, atopic dermatitis and irritative contact dermatitis, and eczema of various exogenous or endogenous origins.

[0072] The wound dressings of the invention are also useful for dermocosmetic use in the treatment of skin relaxation with or without lesions or microlesions, due to the high hydrating power of the polysaccharide, in particular of the HA sodium salt, and the ability to stimulate all the physiological functions of the fibroblasts which lead (over time) not only to skin hydration, but also to regeneration of the skin tissue, which compacts due to increased collagen production by the treated skin fibroblasts.