Compositions for the treatment of wounds

Abstract

The present invention relates to the therapeutic use of a composition for the treatment of cutaneous wounds such as acute wounds, chronic wounds or epidermolysis bullosa wounds. The composition according to the invention is based on ABA-type triblock copolymers, comprising two thermoplastic styrene end blocks A and an elastomeric central block B which is a saturated olefin, comprising at least one resin selected from aromatic resins usable in particular for producing an interface dressing with a framework or support or self-supporting.

Description

Description Title: Compositions for the treatment of wounds technical field

[0001] This disclosure falls within the field of skin wound treatment. The present invention relates in particular to the use of specific compositions for wound treatment. Previous technique

[0002] The local management of a skin wound, regardless of its etiology, presents numerous challenges. In addition to the potential medical complications of wounds and their impact on a patient's quality of life, there is the complexity of organizing often multidisciplinary care and the cost of patient management.

[0003] The treatment of wounds with dressings designated by the term "interface dressings" has long been known, intended to be placed in contact with the wound, ensuring an interface between the wound and an absorbent pad that is placed on the dressing to absorb exudates.

[0004] The choice of dressings is made according to the clinical assessment of the wound, its topography, the condition of the peri-lesional skin, and the sensitivity of the patients.

[0005] Primary dressings, in direct contact with the wound, aim to create conditions that promote rapid and optimal healing. To achieve this, they must ensure good wound moisture balance and allow for effective management of exudate, limiting maceration that encourages bacterial growth.

[0006] Traditional dry cotton compresses and greasy dressings, which tended to adhere to the wound bed and cause traumatic and painful removal, were gradually replaced by so-called modern interfaces. These non-occlusive and non-adhesive interfaces maintain a moist environment in contact with the wound and low adhesion over time, allowing for less frequent dressing changes and reducing the associated risk of infection.

[0007] The URGOTUL® dressing, marketed since 2000 by Laboratoires URGO, is a prime example of an interface dressing. This innovative interface, based on LipidoColloid Technology (LCT), consists of a polyester textile fabric impregnated with hydrocolloid particles of carboxymethylcellulose (CMC), paraffin oil, petrolatum, and polymers. Upon contact with exudate, the dressing's hydrocolloid particles gel and interact with the petrolatum component to form a lipidocolloid film, creating an environment conducive to granulation tissue formation and keratinocyte migration. The dressing thus respects newly formed tissue and the surrounding skin, ensuring atraumatic and painless removal.

[0008] However, the URGOTUL® dressing can be difficult to handle and lacks conformability due to the rigidity of its frame.

[0009] In its ongoing commitment to improving wound care and simplifying the daily lives of caregivers and patients, URGO Research, Innovation and Development (URGO RID) has developed and refined an evolution of the Urgotul® dressing, now free of its textile backing and composed of 100% lipidocolloid mass. This new dressing, the subject of international patent applications published under references W02019 / 012230 and WO 2019 / 012226, is extra-flexible, offers easier handling, and provides greater conformability. It does not stick to gloves and can be manually cut to obtain custom sizes adapted to the dimensions of wounds. It was developed to ensure better conformability to the wound bed, including for irregular wounds or wounds located on anatomically difficult-to-dress areas, such as the face, joints, hands, feet, or interdigital wounds.

[0010] This new interface is therefore recognized for its mechanical characteristics which allow both to create conditions conducive to healing while allowing good handling and applicability of the dressing.

[0011] Nevertheless, there remains a need for new methods to promote wound healing. It would be particularly advantageous to develop methods that not only create conditions conducive to wound healing but also directly influence wound treatment. Summary

[0012] Quite surprisingly, the present inventors have demonstrated that the composition at the base of the interface dressing disclosed in applications WO2019 / 012230 and WO 2019 / 012226 allows, in addition to its very good mechanical characteristics as described in these applications, to directly treat wounds, in particular acute wounds, chronic wounds, but also epidermolysis bullosa wounds, the management of which may sometimes require the administration of corticosteroids in combination with dapsone.

[0013] Also, according to a first aspect, the present invention relates to a composition for use in the treatment of skin wounds, such as acute wounds, chronic wounds, and / or epidermolysis bullosa wounds, said composition comprising:

[0014] - 5 to 20% of a mixture of two triblock copolymers of the styrene-saturated olefin-styrene type, the first having a viscosity between 0.01 and 1 Pa.s as measured in a 5% (w / w) toluene solution and the second having a viscosity between 0.01 and 0.5 Pa.s measured in a 15% (w / w) toluene solution

[0015] - 50 to 80% by weight of at least one plasticizer,

[0016] - 5 to 20% of at least one alpha-methylstyrene type resin with a softening point between 80 and 125°C, preferably between 90 and 110°C,

[0017] it being understood that:

[0018] - when the triblock copolymer content is between 5 and 10% by weight, the resin content is between 15 and 20% by weight, relative to the total weight of the composition and

[0019] - when the triblock copolymer content is greater than 10% by weight, the resin content is between 5 and 20% by weight, relative to the total weight of the composition,

[0020] the percentages being reported in relation to the total weight of the composition. Detailed description of the invention

[0021] Elastomer

[0022] The composition according to the invention comprises a mixture of 2 triblock copolymers of the ABA type.

[0023] In particular, this mixture of two copolymers shall comprise at least one copolymer which has a viscosity between 0.01 and 1 Pa.s measured in a 5% w / w solution in toluene and at least one copolymer having a viscosity between 0.01 and 0.5 Pa.s measured in a 15% (w / w) solution in toluene.

[0024] The sequenced copolymers used in the invention are ABA-type triblock copolymers comprising two thermoplastic terminal blocks A (styrene) and a central elastomer sequence B, which is a saturated olefin. Examples of saturated olefin sequences B are ethylene-butylene, ethylene-propylene, or ethylene-ethylene-propylene.

[0025] For the sake of simplicity, in this description, the polymer blocks constituting the aforementioned copolymers are designated by the nature of their repeating units. Thus, the expression "block" or "styrene A sequence" designates a poly(styrene) sequence and the expression "block" or "saturated olefin sequence" designates a poly(saturated olefin) sequence.

[0026] Saturated central sequence triblock copolymers are well known to those skilled in the art and are, for example, commercially available:

[0027] -by the company KRATON under the name KRATON® G, and in particular the grades KRATON® G1651, KRATON® G1654, KRATON® G 1657, KRATON® G1652 or KRATON® G1650 and by the company KURARAY under the names SEPTON® and in particular the grades 8006 or 8004 for sequenced poly (styrene-ethylene-butylene-styrene) copolymers (abbreviated SEBS);

[0028] -by the company KURARAY under the name SEPTON® for poly (styrene-ethylene-propylene-styrene) sequenced copolymers (abbreviated SEPS) and in particular grades 2005, 2006 or 2063 and for poly (styrene-ethylene-ethylene-propylene-styrene) sequenced polymers (abbreviated SEEPS) and in particular grades 4033, 4044, 4055, 4077 or 4099.

[0029] In the context of the present invention, preferred triblock copolymers SEBS, SEPS or SEEPS having a styrene content of between 25 and 45% by weight relative to the weight of said SEBS, SEPS or SEEPS copolymer.

[0030] Among the copolymers that exhibit a viscosity between 0.01 and 1 Pa.s measured in a 5% (w / w) toluene solution, we can mention the copolymers marketed by KRATON under the grades KRATON® G 1651 and KRATON® G 1654 and the copolymers marketed by the company KURARAY under the grades SEPTON® 2005, 2006, 8006, 4055, 4077, 4044 or 4099.

[0031] Among the copolymers which have a viscosity between 0.01 and 0.5 Pa.s measured in a 15% (w / w) toluene solution, we can mention the copolymers marketed by KRATON under the grades KRATON® G 1650, KRATON® G 1657 and KRATON® G 1652 and the copolymers marketed by KURARAY under the grades SEPTON® 2063 or 4033.

[0032] These viscosities are measured at 30°C using a Brookfield LVI viscometer in a 5% or 15% wt / wt toluene solution depending on the molecular weight of the copolymer.

[0033] In general, the quantity of copolymers in the final composition may be between 5 and 20% by weight, preferably between 7 and 15% by weight, relative to the total weight of the composition.

[0034] Within the framework of the present invention, the use of two sequenced SEBS copolymers will be particularly preferred, and in particular the combination of the copolymers KRATON® G 1654 and KRATON® G 1650 in which KRATON® G 1654 is present in an amount of 5 to 10% by weight, relative to the total weight of the composition and KRATON® G 1650 is present in an amount of 2 to 5% by weight, relative to the total weight of the composition.

[0035] Preferably, this mixture of two copolymers shall therefore comprise at least 5 to 10% by weight of a copolymer which has a viscosity between 0.01 and 1 Pa.s measured in a 5% w / w solution in toluene and at least 2 to 5% of a copolymer having a viscosity between 0.01 and 0.5 Pa.s measured in a 15% (w / w) solution in toluene, relative to the total weight of the composition.

[0036] Resins

[0037] The resins used in the composition according to the invention are aromatic hydrocarbon resins, that is, based solely on aromatic monomers. They differ from aliphatic resins, based solely on aliphatic monomers, or from aliphatic / aromatic resins, based on both aliphatic and aromatic monomers. Without being bound by any particular theory, it appears that these resins exhibit good solubility in the A block of ABA copolymers and reinforce this styrene block, thereby improving the cohesion of the final elastomeric matrix obtained.

[0038] In particular, the aromatic monomer is alpha-methylstyrene. Thus, according to a particularly preferred embodiment, the aromatic hydrocarbon resin is chosen from among the homopolymer and copolymer resins of alpha-methylstyrene.

[0039] The resins used in the compositions according to the invention are alpha-methyl styrene type resins whose softening point is between 80 and 125°C, preferably between 90 and 110°C.

[0040] The softening point is measured according to ISO 4625 (Ring and Bail method).

[0041] Preferably, the resin according to the invention is an alpha-methyl styrene resin having a softening point between 95 and 105°C or between 115 and 125°C or a poly(styrene-co-alpha-methyl styrene) resin having a softening point between 95°C and 115°C.

[0042] Preferably, the resin according to the invention is a poly(styrene-co-alpha-methyl styrene) resin having a softening point between 95°C and 115°C.

[0043] The preferred resins mentioned above are well known to those skilled in the art and are commercially available, for example sold under the following trade names:

[0044] - Sylvares SA 100 and Sylvares SA 120 from Arizona Chemical: alpha-methylstyrene resins with a softening point between 95 and 105°C or between 115 and 125°C respectively,

[0045] - Cray Valley's Cleartack W90 or Norsolène W90 resin: a poly(styrene-co-alpha-methylstyrene) resin with a softening point between 85 and 95°C,

[0046] - Eastman's Kristalex 3100LV, Kristalex F100, Kristalex 3105SD and Kristalex F115 resins: poly(styrene-co-alpha-methylstyrene) resins with a softening point of 100°C, or between 96 and 104°C or 105°C, or between 114 and 120°C respectively.

[0047] In the context of the present invention, the resin is preferably present in an amount of 5 to 20%, preferably 5 to 15% by weight, relative to the total weight of the composition.

[0048] Within the scope of the present invention:

[0049] - when the triblock copolymer content is between 5 and 10% by weight, the resin content is between 15 and 20% by weight, relative to the total weight of the composition and

[0050] - when the triblock copolymer content is greater than 10% by weight, the resin content is between 5 and 20% by weight, relative to the total weight of the composition,

[0051] the percentages being reported in relation to the total weight of the composition.

[0052] In the context of the present invention, the content of triblock copolymers and resin represents 16 to 40% by weight, preferably 20 to 35% by weight, relative to the total weight of the composition.

[0053] The plasticizer

[0054] In order to produce interface dressings, the mixture of copolymers and the resin present in the composition according to the invention are associated with one (or more) plasticizing compound(s).

[0055] The plasticizers that can be used are well-known and designed to improve the stretching, flexibility, extrudability, or processing properties of copolymers. One or more plasticizers may be used for this purpose, if necessary.

[0056] In general, as plasticizers, liquid compounds are preferred, compatible with the saturated olefin central sequence of the aforementioned sequenced copolymers.

[0057] Among the plasticizing compounds that could be used for this purpose, plasticizing mineral oils should be mentioned in particular.

[0058] Alternatively, synthetic products based on liquid mixtures of saturated hydrocarbons can also be used, such as the products marketed by the company TOTAL under the name GEMSEAL® and in particular the product GEMSEAL® 60 which is an isoparaffinic mixture derived from a fully hydrogenated petroleum cut.

[0059] Within the framework of the present invention, plasticizing oils, and in particular mineral oils formed from compounds of a paraffinic or naphthenic nature, or mixtures thereof, will preferably be used in varying proportions.

[0060] Particularly preferred plasticizing mineral oils are formed from mixtures of paraffinic and naphthenic compounds, and especially such mixtures in which the proportion of paraffinic compounds is predominant.

[0061] Among the plasticizing oils that are particularly suitable, we can mention the products marketed by the company SHELL under the names ONDINA® and in particular ONDINA® 919 or the oil marketed by the company PETRO CANADA under the reference PURETOL® 9D or the BLANDOL oil marketed by Sonneborn or even the Pionier 2076P oil marketed by Hansen & Rosenthal.

[0062] In addition to oils, the plasticizer may include petrolatum. The petrolatum used in the compositions of the invention is a commercially available petrolatum conforming to the French Pharmacopoeia.

[0063] In the context of the present invention, petroleum jelly is present in an amount of 1 to 30%, preferably 5 to 25% by weight, relative to the total weight of the composition.

[0064] In the context of the present invention, the plasticizer is present in an amount of 50 to 80%, preferably 60 to 70% by weight, relative to the total weight of the composition.

[0065] Preferably, the plasticizer consists of a mixture of mineral oil and petrolatum. In this case, the mineral oil is present in a quantity ranging from 45 to 60% by weight relative to the total weight of the composition, and the petrolatum is present in a quantity ranging from 5 to 20% by weight relative to the total weight of the composition.

[0066] The composition according to the invention preferably comprises:

[0067] - 5 to 20% by weight of a mixture of two copolymers comprising at least one copolymer which has a viscosity between 0.01 and 1 Pa.s measured in a 5% w / w solution in toluene and at least one copolymer having a viscosity between 0.01 and 0.5 Pa.s measured in a 15% (w / w) solution in toluene.

[0068] - 50 to 80% by weight of a mixture of oil and petroleum jelly,

[0069] - 5 to 20% by weight of a resin chosen from among alpha-methyl styrene resins having a softening point between 95 and 105°C or between 115 and 125°C or a poly(styrene-co-alpha-methyl styrene) resin having a softening point between 95°C and 115°C.

[0070] These compositions are also useful for preparing dressings with or without reinforcement.

[0071] Hydrocolloids

[0072] According to an embodiment of the invention particularly preferred in the context of the production of self-supporting interface dressings, with support or with reinforcement for wound healing, the compositions according to the invention comprise hydrophilic particles of a hydrocolloid (or hydrocolloid particles).

[0073] These particles allow for the painless removal of an interface dressing and the maintenance of a moist environment at the wound site to promote healing.

[0074] For this purpose, a small amount of hydrophilic particles of a hydrocolloid is thus either placed on the surface of the elastomeric matrix once it has been formed or, preferably, dispersed homogeneously within the composition according to the invention.

[0075] By "hydrocolloid" or "hydrocolloid particles" we mean here any compound usually used by people skilled in the art for its ability to absorb aqueous liquids such as water, saline solution or wound exudates.

[0076] Examples of suitable hydrocolloids include pectin, alginates, natural vegetable gums such as Karaya gum, cellulose derivatives such as carboxymethylcelluloses and their alkali metal salts such as sodium or calcium, and synthetic polymers based on acrylic acid salts, known as "superabsorbents", such as the products marketed by CIBA Specialty Chemicals under the name SALCARE® SC91 and mixtures of these compounds.

[0077] Some of these superabsorbents, described as "microcolloids" because they have a particle size of less than 10 micrometers, can of course also be used.

[0078] The preferred hydrocolloids within the scope of the present invention are alkali metal salts of carboxymethylcellulose, and in particular sodium carboxymethylcellulose (CMC).

[0079] The size of hydrocolloid particles is generally between 50 and 100 microns, advantageously around 80 microns.

[0080] In general, the quantity of hydrocolloid particles incorporated in the composition according to the invention will advantageously be less than or equal to 25% by weight, advantageously in the range of 2 to 20% by weight, preferably from 5 to 18% by weight, and even more preferably from 10 to 15% by weight, relative to the total weight of said composition.

[0081] If the hydrocolloid particles are placed on the surface of the elastomeric matrix once it has been formed, their quantity will preferably be in the order of 1 to 10% and more particularly 2 to 5% by weight, relative to the total weight of said elastomeric matrix.

[0082] Choosing a quantity of hydrocolloid particles within these ranges of values ​​is important for the production of an interface dressing, and in particular a self-supporting aerated interface dressing, in order to prevent the gelation of the composition from causing the closure of the through holes during the absorption of exudates.

[0083] Antioxidants

[0084] The composition according to the invention may also include antioxidant agents.

[0085] By "antioxidant agents" we mean here the compounds commonly used by those skilled in the art to ensure the stability of the compounds used in the formulation of compositions, in particular with respect to oxygen, heat, ozone or ultraviolet radiation.

[0086] Examples of suitable antioxidant agents include phenolic antioxidants, such as the products marketed by BASF under the names IRGANOX® 1010, IRGANOX® 565, IRGANOX® 1076.

[0087] In general, these antioxidant agents can be used alone or in combination in an amount of approximately 0.05 to 1% by weight, preferably 0.05 to 0.2% by weight, relative to the total weight of the composition.

[0088] Within the framework of the present invention, the use of the product IRGANOX® 1010 is preferred in an amount between 0.05 and 0.2% by weight, relative to the total weight of the composition.

[0089] Additional assets

[0090] As demonstrated in the experimental section below, the composition according to the present invention possesses inherent healing properties. It therefore allows for the direct treatment of skin wounds.

[0091] However, in order to further improve healing, in addition to antioxidant agents, the composition according to the invention may also include one (or more) other active substance(s) that induce or accelerate healing or that may play a favorable role in the treatment of a wound.

[0092] Among these active substances, the following can be cited in particular as examples:

[0093] - healing agents such as retinol, vitamin A, vitamin E, N-Acetyl Hydroxyproline, Centella Asiatica extracts, papain, silicone, essential oils of thyme, niaouli, rosemary, sage, hyaluronic acid, potassium sucrose octasulfate, sucralfate, allantoin, metformin

[0094] - antibacterial agents such as silver salts or complexes (such as silver sulfates, silver nitrates, silver sulfonamides or silver-based zeolites), zinc or copper salts, metronidazole, neomycin, penicillins, clavulanic acid, tetracyclines, mynocycline, chlorotetracycline, aminoglycosides, amikacin, gentamicin, probiotics;

[0095] - antiseptics such as chlorhexidine, trichlosan, biguanide, hexamidine, thymol, lugol, povidone iodine, benzalkonium chloride and benzethonium chloride;

[0096] - painkillers such as paracetamol, codeine, dextropropoxyphene, tramadol, morphine and its derivatives, corticosteroids and their derivatives;

[0097] - local anesthetics such as lidocaine, benzocaine, dibucaine, pramoxine hydrochloride, bupivacaine, mepivacaine, prilocaine, etidocaine;

[0098] - anti-inflammatories such as non-steroidal anti-inflammatory drugs (NSAIDs), aspirin or acetylsalicylic acid, libuprofen, ketoprofen, flurbiprofen, diclofenac, aceclophenac, ketorolac, meloxicam, piroxicam, tenoxicam, naproxen, indomethacin, naproxcinod, nimesulid, celecoxib, etoricoxib, parecoxib, rofecoxib, valdecoxib, phenylbutazone, niflumic acid, mefenamic acid;

[0099] These active agents may be used in an amount of approximately 0.01 to 20% by weight, preferably 1 to 15% by weight, and preferably 2 to 10% by weight, relative to the total weight of the composition.

[0100] The presence of hydrocolloids in the composition will promote the release of these active agents.

[0101] Of course, the composition according to the invention may also include one or more other compounds known for their action in the cleansing phase, such as:

[0102] - enzymes;

[0103] - urea.

[0104] Adjuvants

[0105] Examples of adjuvants that can be used in compositions according to the invention include compounds known to promote the release of active agents, such as Montanox® 80 or Sepinov® EMT 10, which are commonly used in URGOTUL® products that incorporate active agents.

[0106] These adjuvants may be used in a quantity of approximately 1 to 15% by weight, relative to the total weight of the composition.

[0107] Obviously, the specific embodiments just described can be implemented separately or in any combination thereof.

[0108] The compositions according to the invention make it possible in particular to produce self-supporting interface dressings or interface dressings having a frame or support.

[0109] When preparing an interface dressing, preference will be given to using a composition which includes compounds (copolymers, mineral oil, petroleum jelly, antioxidant and hydrocolloids) of the same nature as, or identical to, those used in the URGOTUL® product.

[0110] Elastomeric matrix

[0111] In order to produce a dressing, the compositions according to the invention will be formed in a thin layer, with through holes, preferably arranged in a distributed manner in said layer to form an elastomeric matrix.

[0112] The invention thus relates, according to another aspect, to the composition as described above for its use in the treatment of wounds, in which said composition is in the form of an elastomeric matrix.

[0113] The through holes can be made by perforation or punching a composition according to the invention previously formed in a thin layer, alone or associated with a temporary support or a protective film usually used for the manufacture of dressings, or by a woven coating on a temporary support.

[0114] Alternatively, the elastomeric matrices according to the invention can be manufactured by hot casting of a composition as described above onto a plate engraved with the pattern retained to form through holes, followed by cooling and demolding.

[0115] In general, the elastomeric matrices according to the invention will have a thickness between 0.4 mm and 2 mm, preferably between 0.5 mm and 1 mm, and even more preferably in the range of 0.6 to 0.7 mm.

[0116] Through holes can be of any geometry and may, for example, have a circular, rectangular, trapezoidal or square cross-section.

[0117] Their surface area will generally be between 1 and 7 mm 2 .

[0118] These holes will be distributed, preferably regularly, with a density such that the total surface area of ​​the holes represents between 20 and 70%, and preferably between 30 and 60% of the total surface area of ​​the dressing.

[0119] According to a preferred embodiment, the polymer matrix, when implemented in an interface dressing, preferably self-supporting, is in the form of an aerated mesh (or grid), preferably with a square mesh, having:

[0120] - a net thickness between 0.4 and 2 mm;

[0121] - a "wire width" (width of the space between two consecutive holes) of between 1 and 10 mm, and preferably between 1 and 5 mm;

[0122] - a weight between 200 and 1700 g / m 2 , and preferably between 300 and 800 g / m 2 .

[0123] According to a particularly preferred embodiment of the invention, such an elastomeric matrix shall be in the form of an open-mesh, square-openwork net having:

[0124] - a net thickness of approximately 750 microns;

[0125] - a wire width (or mesh size) of approximately 0.8 mm;

[0126] - a weight of approximately 390 g / m² 2 .

[0127] For the production of such elastomeric matrices, reference can be made for further details to patent application FR 2936 158.

[0128] It may also be possible to use this elastomeric matrix to coat a reinforcement or support.

[0129] The manufacturing techniques for an interface dressing with reinforcement or support are also well known to those skilled in the art, and one can, for example, refer to the processes described in patent applications WO 00 16725 and FR 2936 159 or WO 2015 / 018720.

[0130] Bandage

[0131] The invention thus relates, according to a particular mode, to the composition as described above for its use in the treatment of wounds, in which said composition is in the form of an elastomeric matrix, said elastomeric matrix is ​​included in an interface dressing.

[0132] Such an interface dressing is preferably a self-supporting interface dressing comprising an elastomeric matrix in the form of a thin layer having through holes to allow exudate to pass through, obtained from a composition comprising:

[0133] - 5 to 20% of a mixture of two triblock copolymers of the styrene-saturated olefin-styrene type, the first having a viscosity between 0.01 and 1 Pa.s as measured in a 5% (w / w) toluene solution and the second having a viscosity between 0.01 and 0.5 Pa.s measured in a 15% (w / w) toluene solution

[0134] - 50 to 80% by weight of at least one plasticizer,

[0135] - 5 to 20% of at least one alpha-methylstyrene type resin with a softening point between 80 and 125°C, preferably between 90 and 110°C,

[0136] it being understood that:

[0137] - when the triblock copolymer content is between 5 and 10% by weight, the resin content is between 15 and 20% by weight, relative to the total weight of the composition and

[0138] - when the triblock copolymer content is greater than 10% by weight, the resin content is between 5 and 20% by weight, relative to the total weight of the composition,

[0139] the percentages being reported in relation to the total weight of the composition.

[0140] In order to protect the composition from the external environment, the interface dressing may be covered, preferably on each of its sides, by a temporary protective film which will be removed before use by the user.

[0141] To further facilitate the handling of the interface dressing, particularly if it is self-supporting, these two temporary protective films can be replaced by a single protector as described in patent application WO 2008 / 145884 or in patent application W02015 / 018720, whose particular structure facilitates the application of the dressing to the wound.

[0142] Therapeutic application

[0143] The composition according to the present invention is used in the treatment of skin wounds. The concept of a "skin wound" is well known to those skilled in the art. It refers to an injury to the skin caused by various factors such as cuts, grazes, burns, or ulcerations. Skin wounds can be superficial (affecting only the epidermis) or deeper (reaching the dermis or underlying tissues) and can result from physical trauma, burns, infections, or medical conditions such as diabetes.

[0144] Wounds can be "acute," often caused by sudden trauma and healing within a predictable timeframe, following a normal healing process. Acute wounds can include second-degree burns, abrasions, traumatic wounds, or post-operative wounds.

[0145] Wounds can also be "chronic," often linked to underlying medical conditions such as diabetes, leg ulcers, or pressure sores. Chronic wounds do not heal within the usual timeframe and can persist for weeks or even months. A wound is considered chronic if it shows no signs of healing after 4 to 6 weeks. Examples of chronic wounds include pressure sores and ulcers, such as diabetic foot ulcers.

[0146] Within the framework of the present invention, the treated skin wound may be an acute wound, a chronic wound, or an epidermolysis bullosa wound.

[0147] Epidermolysis bullosa is a rare genetic disorder (1 case per 50,000 births) that disrupts the cohesion between the different tissues and cells of the epidermis. Epidermolysis bullosa results in extremely fragile skin that tears easily or develops sores and blisters with even slight friction, stress, and minor injuries. This disease is classified as a connective tissue disorder, and all identified hereditary forms are caused by genetic mutations. There are four main forms of epidermolysis bullosa: epidermolysis bullosa simplex, junctional epidermolysis bullosa, dystrophic epidermolysis bullosa, and Kindler syndrome. These categories are generally distinguished by the point of separation between the outer layer of skin (the epidermis) and the dermis (the innermost layer of skin). Currently, there is no cure for epidermolysis bullosa.Patient care primarily consists of relieving symptoms, preventing infection, and aiding in healing.

[0148] The present invention is illustrated in the non-limiting examples shown below. Examples

[0149] Example 1: Preparation of the composition according to the invention

[0150] The composition was developed using the following components:

[0151] Elastomer: sequenced copolymer of poly(styrene-ethylene-butylene-styrene) (abbreviated SEBS):

[0152] - KRATON® G 1654 ES viscosity at 5% (w / w) in toluene: 0.02 Pa.s

[0153] - KRATON® G 1650 EU viscosity at 15% (w / w) in toluene: 0.2 Pa.s

[0154] Plasticizer: Pioneer 2076P marketed by Hansen & Rosenthal

[0155] Vaseline: Codex® A vaseline marketed by the company AIGLON

[0156] Antioxidant: IRGANOX® 1010 marketed by BASF [01571 Hydrocolloid: Sodium carboxymethylcellulose CMC BLANOSE® 7H4XF marketed by the company ASHLAND,

[0158] Resin: Kristalex 3105SD, poly(styrene-co-alpha-methyl styrene) resin with a softening point of 105°C, marketed by Eastman.

[0159] The proportions of each component, expressed as a percentage by weight, are presented in Table 1 below:

[0160] [Table 1] Constituent % by weight Vaseline Codex® A 12,000 Pioneer 2076P 53,500 Carboxymethylcellulose 13,000 sodium CMC BLANOSE® 7H4XF KRATTON® G 1650 EU 3,500 KRATON® G 1654 ES 7,800 IRGANOX® 1010 0.200 Kristalex 3105SD 10,000

[0161] Composition manufacturing

[0162] In a vertical mixer, the plasticizer, hydrocolloid and petroleum jelly were successively introduced at a set temperature of 90°C and stirred until a homogeneous mixture was obtained.

[0163] The copolymers, antioxidant, and resin were then added while stirring, and the temperature was raised to 150°C. The mixture was stirred until homogeneous. The mixer was then placed under vacuum to remove any remaining air bubbles.

[0164] We then let it cool, and then we drained the blender.

[0165] Subsequently, polymeric matrices were produced from the compositions to be tested, by applying high pressure using a hydraulic press according to the following protocol:

[0166] The two platens of the hydraulic press were preheated. A non-stick plastic film, for example, a silicone-fluorinated polyester film (with the silicone-fluorinated side facing away from the lower platen), was placed on the lower platen. Approximately 12 g of one of the described compositions was then deposited on this surface and covered with a silicone-coated polyester film (with the silicone side in contact with the composition). Two 0.75 mm spacers were placed between the two polyester films at the ends of the lower platen, and the assembly was subjected to a pressure of 200 bar and a temperature of approximately 90 to 100°C.

[0167] The plates thus made were allowed to cool and their thicknesses were checked with a micrometer in order to obtain a model with a thickness of around 650µm.

[0168] Example 2: Application of the composition according to the invention for the treatment of wounds

[0169] METHODOLOGY

[0170] In order to determine the effects of the composition according to the present invention, the polymeric matrix obtained according to Example 1 was applied as a dressing to chronic, acute wounds and to skin lesions of epidermolysis bullosa.

[0171] A multicenter, non-comparative clinical study was conducted in patients with acute or chronic wounds or epidermolysis bullosa skin lesions. The study was carried out in hospital departments or private practices specializing in clinical geriatrics, dermatology, general surgery, plastic and reconstructive surgery, burn units, vascular medicine and surgery, angiology, and phlebology across 30 participating centers.

[0172] A total of 81 patients meeting the eligibility criteria were included, and results were obtained for 78 of them (3 patients withdrew from the study after inclusion). Included patients were followed for a maximum of 4 weeks, including a maximum of 5 assessment visits (Day 0 / Week 1 / Week 2 / Week 3 and Week 4).

[0173] The patients recruited were hospitalized and / or outpatients with an acute wound (N=56), a chronic wound (N=19) or a skin lesion of epidermolysis bullosa (N=6).

[0174] The effectiveness of the trial dressing was judged on the evolution of the wound surface at the end of the 4 weeks of treatment.

[0175] The main judgment criterion was the relative planimetric evolution (expressed in %) of the wound surface, calculated from centralized planimetric measurements, according to the Math formula. 1 next:

[0176] [Math. 1] Evolution of the surface (%) = [(S TO - STlast) / ST0] x 100

[0177] ST0: Wound surface area measured on the day of inclusion

[0178] STlast: Wound surface area at the last available planimetric assessment

[0179] Other criteria, including pain upon dressing removal, the condition of the perilesional skin, the clinical appearance of the wound, and the acceptability of the dressing by the healthcare team, favorable evolution of venous or mixed leg ulcers with a predominantly venous component, the healing rate, the healing time, and the frequency of dressing changes, were also evaluated. f01801 RESULTS

[0181] Main criterion:

[0182] At the end of the four weeks of treatment with the dressing, a relative reduction in wound surface area of ​​-90%, -81% and -47% (mean values) and -100%, -100%, -61.5% (median values) is observed for skin lesions of epidermolysis bullosa, acute wounds and chronic wounds respectively.

[0183] Secondary criteria:

[0184] Percentage of wounds healed and time to achieve wound healing: At the end of the 4 weeks of treatment, more than half of the acute wounds (59%) healed within 14.5 days (median value), 16% of chronic wounds healed within 27 days (median value) and 60% of epidermolysis bullosa lesions healed within 18 days (median value).

[0185] Assessment of pain on dressing removal: During the 4 weeks of follow-up, regarding the characteristics of dressing removal, more than 90% of removals were carried out without pain, during investigator care, (all types of wound combined).

[0186] Evaluation of the perilesional skin condition: At baseline, the perilesional skin (PPL) was considered "altered" in 19 patients (acute wound group). After 4 weeks of treatment with the dressing, the PPL was considered "altered" in only 7 patients. This favorable outcome was also observed in the EB group, with no PPL considered altered at the end of the 4 weeks of treatment. Unlike the other two groups, there was no change in the condition of the PPL with the dressing in the chronic wound group between day 0 and week 4 (at days 0 and 4: 12 patients with PPL considered altered). For all wounds, when the perilesional skin is altered, it is predominantly "erythematous" in more than 40% of cases.

[0187] Favorable evolution of venous or mixed leg ulcers with predominantly venous: Among the 18 ulcers, 9 (50%) ulcers treated with the dressing under study have a relative surface area reduction greater than 40% (RRS>40%), indicating a high probability of re-epithelialization of leg ulcers after 20-24 weeks of treatment.

[0188] Acceptability criteria: 1077 procedures were documented in this study. Dressing acceptability was assessed during scheduled visits and during procedures performed between assessments. Overall, dressing removal was rated as "very easy" or "easy" in 99% of cases, with the dressing removed in one piece in 96% of cases, while preserving newly formed tissue in 98% of cases, thus demonstrating good dressing acceptability. Furthermore, dressing degradation was rated as "absent" in 97% of cases.

[0189] Investigator physicians' recommendation level: The dressing's acceptability results are supported by a recommendation level of 9 / 10 (median value) from the investigator physicians in the acute wounds and epidermolysis bullosa skin lesions group and 8 / 10 (median value) in the chronic wounds group. This demonstrates the good acceptability of the dressing as judged by the investigator physicians.

[0190] CONCLUSION

[0191] This clinical study demonstrates positive results in terms of relative wound surface area reduction, reaching over 80% in the acute wound group (average value), over 89% in the epidermolysis bullosa skin lesion group (average value), and nearly 47% in the chronic wound group (average value). Furthermore, the study showed healing rates of 59%, 16%, and 60% for acute, chronic, and epidermolysis bullosa skin lesions, respectively, after 4 weeks of treatment.

[0192] The good results on the acceptability of the dressing prepared according to the invention are supported by a level of recommendation by the investigating physicians of 9 / 10 (median value) of the dressing in the acute wounds and skin lesions of epidermolysis bullosa group and of 8 / 10 (median value) in the chronic wounds group, which testifies to the good acceptability of the dressing judged by the investigating physicians.

[0193] The dressing's tolerability is similar to that reported in the literature. Therefore, the dressing was well tolerated in this study.

[0194] The dressing composition according to the present invention represents a good therapeutic alternative in the local management of acute wounds, skin lesions of epidermolysis bullosa and chronic wounds, from the granulation phase until complete healing.

Claims

Demands

1. Composition for use in the treatment of a skin wound, said composition comprising: 5 to 20% of a mixture of 2 triblock copolymers of the type styrene - saturated olefin - styrene, a first one which has a viscosity between 0.01 and 1 Pa.s as measured in a 5% (w / w) solution in toluene and a second one which has a viscosity between 0.01 and 0.5 Pa.s measured in a 15% (w / w) solution in toluene; 50 to 80% by weight of at least one plasticizer, 5 to 20% of at least one alpha-methylstyrene type resin with a softening point between 80 and 125°C, preferably between 90 and 110°C, it being understood that: when the triblock copolymer content is between 5 and 10% by weight, the resin content is between 15 and 20% by weight, relative to the total weight of the composition, and when the triblock copolymer content is greater than 10% by weight, the resin content is between 5 and 20% by weight, relative to the total weight of the composition, the percentages being relative to the total weight of the composition.

2. Composition for its use according to claim 1, wherein said skin wound is selected from the group consisting of chronic wounds, acute wounds, and epidermolysis bullosa wounds.

3. Composition for its use according to claim 2, wherein said wound is an epidermolysis bullosa wound.

4. Composition for its use according to any one of claims 1 to 3, wherein the resin is a poly(styrene-co-alpha-methyl styrene) resin having a softening point between 95°C and 115°C.

5. Composition for its use according to any one of claims 1 to 4, wherein the plasticizer consists of a mixture of mineral oil and petrolatum.

6. Composition for use according to any one of claims 1 to 5, wherein said composition comprises hydrocolloid particles in an amount less than or equal to 25% by weight, relative to the total weight of the composition.

7. Composition for use according to any one of claims 1 to 6, wherein said composition is in the form of an elastomeric matrix.

8. Composition for its use according to claim 7, wherein said elastomeric matrix is ​​self-supporting and has through holes.

9. Composition for its use according to claim 7 or 8, wherein said elastomeric matrix is ​​included in an interface dressing.

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