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    • 专利摘要:
    The present invention relates to a dressing for the controlled and prolonged release of active. The present invention relates in particular to the use of a resin selected from aromatic resins to promote the release of active (s) in an elastomeric matrix.
    公开号:FR3068974A1
    申请号:FR1756590
    申请日:2017-07-12
    公开日:2019-01-18
    发明作者:Claire Bouvier；Sebastien Very
    申请人:Urgo Recherche Innovation et Developpement；
    IPC主号:
    专利说明:

    DRESSING ALLOWING CONTROLLED AND SUSTAINED RELEASE OF ASSETS
    ABSTRACT
    The present invention relates to the use of a resin as an active release agent.
    The present invention relates in particular to the use of a resin chosen from aromatic resins to promote the release of active agent (s) in an elastomeric matrix, as well as to a composition comprising it.
    STATE OF THE PRIOR ART
    Wound healing usually depends on the proliferation of new epithelial, endothelial and connective tissue. It therefore brings into play a set of nested and interconnected events by successive and reciprocal inductions of the various cells involved. Each step is induced by the previous one and can therefore only take place if the previous step ends. It is a complex process underpinned by successive waves of growth factors and inflammatory mediators.
    The pharmaceutical market currently offers many topical preparations recommended to promote wound healing. In fact, their action results from the complementarity of the various products which compose them and give them, within a certain limit, their healing property. They protect the wounds from the surrounding environment with an antiseptic coating. They stimulate the development of vascularisation and regulate epidermisation. These topical forms consist mainly of a lipid mixture (lanolin, petroleum jelly, glycerin ...) in which acids (salicylic, benzoic, malic), minerals (zinc oxide, titanium) or halides (iodide) are added. of starch). Some also contain collagen, fibrinogen, enzymatic serum proteolysate (supply of amino acids) or even vitamins (vitamin A) and hormones (4-chloro testosterone acetate). There is also an ointment (Madécasol tulgras from SYNTEX Laboratories) whose healing action is brought about by the association of a mixture of three triterpenes extracted from the roots of the plant Centella asiatica (TCEA). These compounds stimulate the biosynthesis of collagen and glycoaminoglycans. Patent FR 2,809,310 describes the use of metformin in a topical composition having a healing and / or angiogenic effect. The various dosage forms of compositions envisaged are of the oil, cream, foam, liniment, lotion, ointment, liquid, gel, milk, powder or spray type.
    However, the local application of active ingredient (s) in the form of a topical composition needs to be frequently repeated to ensure an effect on wound healing. However, for many wounds, it is necessary to apply a local treatment promoting healing for several days, even several weeks, to obtain good healing, and to avoid the renewal of treatment to limit the risks of infection linked to handling the compositions.
    It would therefore be desirable to have a device, such as a dressing, comprising an active ingredient, for effectively treating wounds for several days. For economic reasons, the dressing should ideally be applied for a period of around 72 hours. Too frequent a change of the dressing induces additional costs having regard to the costs of nursing staff necessary for the change of said dressing. Changing too often can also increase the risk of infections. When the dressing is removed, the wound is exposed to bacteria present in the environment.
    However, when the active ingredient has a strong affinity for exudates, the latter tends to be released too quickly onto the wound, so that a peak in concentration of the active ingredient is released by the dressing within hours of its application. application, and the beneficial effects of the treatment do not last more than a few hours. On the contrary, the dressing should allow a controlled and continuous release of the active ingredient for several days, in particular for approximately three days. In particular, to reach a satisfactory level of response at the level of wound receptors, a sufficient quantity of active agent should be released as soon as the device is applied, then a weaker but continuous release of active agent should be maintained throughout the duration of application of the device on the wound in order to maintain the desired effects. It is, in other words, to administer a particular release profile involving a bolus in the first times of application of the formulation, then the maintenance of a lower level of release of active throughout the duration of treatment.
    SUMMARY OF THE INVENTION
    The present invention aims to respond to these problems, by proposing a composition capable of being used in a device of the dressing type comprising an active agent, allowing it to be released according to a continuous and controlled profile for several days.
    Thus, the present invention has made it possible to develop a specific composition based on triblock copolymers of the ABA type, comprising two thermoplastic end blocks A styrene and an elastomeric central block B which is a saturated olefin, allowing the preparation of an elastomeric matrix likely to be implemented in a dressing, which may be in the form of a self-supporting dressing, said matrix allowing release of active ingredient (s) according to a continuous and controlled profile for several days.
    More specifically, it has been discovered, and this constitutes the basis of the present invention, that the use of an aromatic resin present in the composition in a predetermined weight quantity, allows an enhanced release of active ingredient (s) by compared to the dressing not containing said resin.
    The use of specific resins increases the percentage of active salt released.
    The addition of specific resins also makes it possible to reduce the viscosity of the elastomeric mixture and to mechanically reinforce the elastomeric matrix. This is particularly advantageous in the process for manufacturing the elastomeric matrix. The composition, due to its reduced viscosity, can be coated more easily on a frame. In the case of a self-supporting dressing, improving the cohesion of the elastomeric matrix allows better molding and demolding of the latter. In addition, because of the specific resins used, the manufacturing temperature of the composition can be reduced by approximately 10 ° C., which makes it possible to introduce into the mixture components sensitive to thermal treatments, such as active agents for example.
    According to a preferred embodiment, the dressing according to the invention does not adhere to surgical latex gloves.
    Thus according to a first aspect, the subject of the present invention is a composition comprising:
    - 5 to 20% by weight of at least one triblock copolymer of the ABA type, comprising two thermoplastic end blocks A styrene and a central elastomer block B which is a saturated olefin or of a mixture of triblock copolymers of the ABA type, comprising two thermoplastic terminal blocks A styrene and an elastomer central block B which is a saturated olefin, based on the total weight of the composition
    - 50 to 80% by weight of at least one plasticizer,
    - 0.5 to 15% by weight of an alpha methylstyrene resin with a softening point between 80 and 125 ° C, preferably between 90 and 110 ° C
    - 0.1 to 15% of an active ingredient, the percentages being based on the total weight of the composition
    According to a second aspect, the present invention relates to an elastomeric matrix obtained from such a composition and an interface dressing, with support or self-supporting comprising said elastomeric matrix.
    Finally, the invention also relates to the use of an alphamethyl styrene type resin to promote the release of active ingredient in a composition, in particular used in a dressing.
    DETAILED DESCRIPTION
    elastomer
    The composition according to the invention comprises at least one triblock copolymer of the ABA type.
    The block copolymers used in the context of the invention are triblock copolymers of the ABA type comprising two thermoplastic end blocks A styrene and a central elastomer block B which is a saturated olefin. The blocks B of saturated olefins are for example ethylene-butylene, ethylene-propylene or ethyleneethylene-propylene blocks.
    For the sake of simplicity, in the present description, the polymer blocks constituting the abovementioned copolymers are designated by the nature of their recurring units. Thus, the expression "block" or "styrene block A" denotes a poly (styrene) block and the expression "block" or "saturated olefin block" denotes a poly (saturated olefin block).
    According to one embodiment of the invention, the composition comprises a mixture of two copolymers, said mixture comprising at least one copolymer which has a viscosity of between 0.01 and 1 Pa.s measured in a solution at 5% mass / mass in toluene and at least one copolymer having a viscosity of between 0.01 and 0.5 Pa.s measured in a 15% solution (mass / mass) in toluene.
    Triblock copolymers with a saturated central block are well known to those skilled in the art and are for example marketed:
    - 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 grades 8006 or 8004 for poly (styrene-ethylenebutylene-styrene) block copolymers (abbreviated SEBS);
    -by the company KURARAY under the name SEPTON® for poly (styrene-ethylene-propylene-styrene) block copolymers (abbreviated SEPS) and in particular grades 2005,2006 or 2063 and for poly (styrene-ethylene- ethylenepropylene-styrene) (abbreviated as SEEPS) and in particular grades 4033,4044, 4055, 4077 or 4099.
    Among the copolymers which have a viscosity of between 0.01 and 1 Pa.s measured in a 5% solution (mass / mass) in toluene, mention may be made of the copolymers marketed by the company 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.
    Among the copolymers which have a viscosity of between 0.01 and 0.5 Pa.s measured in a 15% solution (mass / mass) in toluene, mention may be made of the copolymers marketed by the company Kraton under the grades Kraton® G 1650, KRATON® G 1657 and KRATON® G 1652 and the copolymers marketed by the company KURARAY under the grades SEPTON® 2063 or 4033.
    These viscosities are measured at 30 ° C. using a Brookfield model LVI viscometer in a solution in toluene at 5% or 15% w / w depending on the molecular weight of the copolymer.
    In the context of the present invention, the 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 are preferred.
    Generally, the amount of copolymers in the final composition may be between 5 and 20% by weight, preferably between 7 and 15% by weight, based on the total weight of the composition.
    Resins
    The resins used in the composition according to the invention are aromatic hydrocarbon resins, that is to say based on aromatic monomers only. They are distinguished from aliphatic resins, based on aliphatic monomers only, or aliphatic / aromatic resins based on aliphatic and aromatic monomers. Without wishing to be bound by any theory, it seems that these resins have good solubility in block A of ABA copolymers and reinforce this styrene block, which improves the cohesion of the final elastomeric matrix obtained.
    It has in fact been discovered that the use of an aromatic resin present in the composition in a predetermined weight quantity, allows an enhanced release of active ingredient (s) compared to the dressing not containing said resin. This was particularly unexpected since the resin brings cohesion to the elastomeric matrix. We therefore expected a priori that the active ingredients are trapped in the elastomeric matrix by the addition of such a resin. On the contrary, the resin facilitates and improves the release of the active ingredient. This can have an economic advantage since it is possible to use a lesser amount of active ingredient (s), generally the most expensive compounds, in the composition, for the same released quantity. Also, the release profile of the extended active is more interesting.
    In particular, the aromatic monomer is alpha-methyl styrene. Thus, according to a particularly preferred embodiment, the aromatic hydrocarbon resin is chosen from resins of homopolymers and copolymers of alpha-methyl-styrene.
    Among the aromatic resins tested, a number of them were not entirely satisfactory. Indeed, certain grades of resin, because of their high softening point, require to be heated to high temperatures (above 140 ° C.) to produce the composition of the invention. By working at such temperatures, there is a risk of evaporation of the plasticizer. When hydrocolloids (such as carboxymethylcellulose) or active ingredients are added to the composition, they risk being degraded.
    Thus, the resins used in the compositions according to the invention are resins of the alpha-methyl styrene type, the softening point of which is between 80 and 125 ° C, preferably between 90 and 110 ° C.
    The softening point is measured according to ISO 4625 (Ring and Bail method).
    Preferably, the resin according to the invention is an alpha-methyl styrene resin having a softening point located 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.
    The above preferred resins are well known to those skilled in the art and are available commercially, for example sold under the following trade names:
    - Sylvares SA 100 and Sylvares SA 120 of Arizona Chemical: alpha-methyl styrene resins having a softening point between 95 and 105 ° C or between 115 and 125 ° C respectively,
    - Cleartack W90 or Norsolene W90 resin from Cray Valley: poly resin (styrene-coalpha-methylstyrene) with a softening point between 85 and 95 ° C,
    - Kristalex 3100LV, Kristalex F100, Kristalex 3105SD and Kristalex Fl 15 resins from Eastman: 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.
    In the context of the present invention, the resin is preferably present in an amount of 0.5 to 15%, preferably 2 to 10% by weight, based on the total weight of the composition.
    The plasticizer
    In order to produce interface dressings, the mixture of copolymers and the resin present in the composition according to the invention are combined with one (or more) plasticizer compound (s).
    The plasticizers which can be used are well known and intended to improve the stretching, flexibility, extrudability or processing properties of the copolymers. One or more plasticizers can be used for this purpose if necessary.
    In general, as plasticizers, liquid compounds are preferred which are compatible with the saturated olefin central block of the abovementioned block copolymers.
    Among the plasticizing compounds which may be used for this purpose, particular mention will be made of plasticizing mineral oils.
    Alternatively, one can also use synthetic products based on liquid mixtures of saturated hydrocarbons such as for example the products sold 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.
    In the context of the present invention, use will preferably be made of plasticizing oils and in particular mineral oils formed from paraffinic or naphthenic compounds, or mixtures thereof, in variable proportions.
    Particularly preferred plasticizing mineral oils are formed from mixtures of compounds of paraffinic and naphthenic nature, and in particular of such mixtures in which the proportion of compounds of paraffinic nature is predominant.
    Among the plasticizing oils which are particularly suitable, mention may be made of the products sold by the company SHELL under the names ONDINA® and in particular ONDINA® 919 or the oil sold by the company PETRO CANADA under the reference PURETOL® 9D or the oil BLANDOL sold by Sonnebom or the Pionier 2076P oil sold by Hansen & Rosenthal.
    In addition to oils, the plasticizer may include petroleum jelly. The petrolatum used in the compositions of the invention is a petrolatum conforming to the French Pharmacopoeia available commercially.
    In the context of the present invention, petrolatum is present in an amount of 1 to 30%, preferably 5 to 25% by weight, based on the total weight of the composition.
    In the context of the present invention, the plasticizer is present in an amount of 50 to 80%, preferably 60 to 70% by weight, based on the total weight of the composition.
    Preferably, the plasticizer consists of a mixture of mineral oil and petroleum jelly, the mineral oil being present in an amount ranging from 45 to 60% by weight relative to the total weight of the composition, the petroleum jelly being present in a amount ranging from 5 to 20% by weight relative to the total weight of the composition.
    Active:
    In addition to the elastomer, the composition according to the present invention comprises at least one active agent which makes it possible to induce or accelerate scarring or which can have a favorable role in the treatment of a wound.
    Among these active substances, there may be mentioned, in particular, as examples:
    - healing agents such as retinol, vitamin A, vitamin E, N-Acetyl Hydroxyproline, Centella Asiatica extracts, papain, silicone, essential oils of thyme, niaouli, rosemary, sage, l hyaluronic acid, sucrose potassium octasulfate, sucralfate, allantoin, metformin;
    - antibacterial agents such as silver salts or complexes (such as silver sulphates, silver nitrates, silver sulphonamides or even silver-based zeolites), zinc or copper salts , metronidazole, neomycin, penicillins, clavulanic acid, tetracyclines, mynocycline, chlorotetracycline, aminoglycosides, amikacin, gentamicin, probiotics;
    - antiseptics such as chlorhexidine, trichlosan, biguanide, hexamidine, thymol, lugol, povidone iodine, benzalkonium and benzethonium chloride;
    - painkillers such as paracetamol, codeine, dextropropoxyphene, tramadol, morphine and its derivatives, corticoids and their derivatives;
    - local anesthetics such as lidocaine, benzocaine, dibucaine, pramoxine hydrochloride, bupivacaine, mepivacaine, prilocaine, etidocaine;
    - anti-inflammatory drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin or acetylsalicylic acid, ibuprofen, ketoprofen, flurbiprofen, diclofenac, aceclophenac, ketorolac, meloxicam, piroxicam, tenoxicam, naproxen, indomethacin, naproxcinod, nimesulid, celecoxib, etoricoxib, parecoxib, rofecoxib, valdecoxib, phenylbutazone, niflumic acid, mefenamic acid;
    Of course, the composition according to the invention can also comprise one or more other compounds known for their action in the detersion phase, for example:
    - enzymes;
    - urea.
    Preferably, the healing agent is chosen from the healing agents retinol, vitamin A, vitamin E, N-Acetyl Hydroxyproline, extracts of Centella Asiatica, papain, silicone, essential oils of thyme, niaouli, rosemary, sage, hyaluronic acid, sucrose potassium octasulfate, sucralfate, allantoin, metformin, and preferably, the healing agent is metformin.
    The composition according to the invention comprises 0.1 to 15% of active agents, preferably 1 to 10% by weight, relative to the total weight of the composition.
    metformin
    Metformin is an oral antidiabetic in the family of normoglycemic biguanides used in the treatment of type 2 diabetes. Its role is to decrease the insulin resistance of the body intolerant to carbohydrates and to reduce hepatic neoglucogenesis. The method of administration of metformin is by mouth. Metformin is absorbed from the small intestine, circulates in the blood in an unfixed fashion and is excreted, unchanged, by the kidneys. Its mechanism of action is complex and has not yet been fully elucidated. Metformin is a normoglycemic agent: it does not act on the secretion of insulin, nor on the sensitivity to insulin of glucose-using tissues (muscles, adipose tissues). Metformin also has a role in the inhibition of neoglucogenesis, by inhibiting mitochondrial glycerophosphate dehydrogenase, and in the membrane transport of glucose (reduction of its intestinal resorption). It also increases the release of Glucagon-like peptide-1, inhibits the glucagon pathway, increases the production of lactates by enterocytes.
    According to a preferred embodiment, the metformin used is in the form of a metformin hydrochloride.
    Preferably, the particle size of metformin, when it is calculated according to the Fraunhoffer optical model between 0.375 μm and 2000 μm, measured by laser with the dry powder module, meets the following characteristics:
    - d50 <300pm, preferably d50 <200pm
    - d90 <600pm, preferably d90 <510pm.
    Preferably, in the context of the present invention, the particle size distribution of metformin is unimodal.
    In the context of the present invention, the amounts of metformin introduced into the dressings are from 0.5 to 15% by weight, preferably 1 to 10% by weight, relative to the total weight of the elastomeric matrix.
    hydrocolloid
    According to an embodiment of the invention which is 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 particles hydrocolloid).
    These particles allow the painless removal of an interface dressing and the maintenance of a moist environment at the level of the wound in order to promote healing.
    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 formed or, preferably, dispersed homogeneously within the composition according to the invention.
    The term “hydrocolloid” or “hydrocolloid particles” is intended to denote here any compound usually used by those skilled in the art for its ability to absorb aqueous liquids such as water, physiological saline or exudates from a wound.
    As suitable hydrocolloids, mention may be made, for example, of pectin, alginates, natural vegetable gums such as in particular Karaya gum, cellulose derivatives such as carboxymethylcelluloses and their alkali metal salts such as sodium or calcium, as well than synthetic polymers based on acrylic acid salts, known under the name superabsorbents, such as for example the products sold by the company CIBA Specialty Chemicals under the name SALCARE® SC91 as well as mixtures of these compounds.
    Some of these superabsorbents qualified as “microcolloids” because they have a particle size of less than 10 micrometers can of course also be used.
    The hydrocolloids preferred in the context of the present invention are the alkali metal salts of carboxymethylcellulose, and in particular sodium carboxymethylcellulose (CMC).
    The size of the hydrocolloid particles is generally between 50 and 100 microns, advantageously of the order of 80 microns.
    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 of the order of 2 to 20% by weight, preferably 5 to 18% by weight, more preferably from 10 to 15% by weight, based on the total weight of said composition.
    If the hydrocolloid particles are placed on the surface of the elastomeric matrix once it has formed, their quantity will preferably be of the order of 1 to 10% and more particularly of 2 to 5% by weight, based on the total weight of said elastomeric matrix.
    The choice of a quantity of hydrocolloid particles included in these ranges of values is important for the production of an interface dressing, and in particular a ventilated, self-supporting interface dressing, in order to prevent the gelation of the composition from causing closing the through holes when absorbing exudates.
    Tackifying resin
    The composition according to the invention can also comprise at least one tackifying resin to give them an adhesive character facilitating their positioning on the wound.
    The tackifying resins which can optionally be used in the composition of the according to the invention are chosen in particular from low molecular weight polyisobutylenes. In general, the use of hydrogenated resins such as the Escorez® resins of the 5000 series is preferred, and even more preferably the Escorez resin.
    5380®.
    antioxidants
    The composition according to the invention can also comprise antioxidant agents.
    The term “antioxidant agents” is intended to denote here the compounds commonly used by those skilled in the art to ensure the stability of the compounds used in the formulation of the compositions, in particular with respect to oxygen, heat, ozone or ultraviolet radiation.
    As examples of suitable antioxidant agents, mention may in particular be made of phenolic antioxidants such as in particular the products sold by the company BASF under the names IRGANOX® 1010, IRGANOX® 565, IRGANOX® 1076.
    In general, these antioxidant agents can be used alone or in combination in an amount of the order of 0.05 to 1% by weight, preferably from 0.05 to 0.2% by weight, based on the total weight. of the composition.
    In the context of the present invention, the use of the product IRGANOX® 1010 is preferred in an amount of between 0.05 and 0.2% by weight, relative to the total weight of the composition.
    adjuvant
    As adjuvants which may be used in the compositions according to the invention, mention may be made of compounds known to promote the release of active agents, such as, for example, the products Montanox® 80 or Sepinov® EMT 10 (salt copolymer 2methyl-2 [(1-oxo-2-propenyl) amino] -1-propanesulfonic acid and 2-hydroxyethyl ester of propenoic acid or of the mixture of 2-octyl-1-dodecanol, of D- xylopyranoside, 2octyldodecyl and polyethylene glycol 30 dipolyhydroxystearate) which are commonly used in URGOTUL® products which incorporate active agents.
    These adjuvants may be used in an amount of the order of 0.01 to 10% by weight, preferably 0.05 to 5% by weight, relative to the total weight of the elastomeric matrix.
    Obviously, the particular embodiments which have just been described can be implemented separately or according to any one of their combinations.
    The compositions according to the invention make it possible in particular to produce self-supporting interface dressings or interface dressings having a frame or a support.
    In the context of the production of an interface dressing, it is preferable to use a composition which comprises compounds (copolymers, mineral oil, petrolatum, antioxidant and hydrocolloids) of the same nature as, or identical to, those used in the URGOTUL® product.
    Elastomeric matrix
    In order to make 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.
    Another subject of the invention is therefore, according to another aspect, an elastomeric matrix obtained from a composition according to the invention as described above.
    The through holes can be made by punching or punching a composition according to the invention previously formed in a thin layer, alone or associated with a temporary support or with a protective film usually used for the manufacture of a dressing, or even by coating. screened on a temporary support.
    Alternatively, the polymeric matrices in accordance with the invention can be produced by hot casting of a composition as described above on a plate engraved with the pattern selected to form through holes, followed by cooling and demolding.
    In general, the polymer matrices according to the invention will have a thickness of between 0.4 mm and 2 mm, preferably between 0.5 mm and 1 mm, more preferably of the order of 0.6 to 0.7 mm.
    The through holes can be of any geometry and will for example have a circular, rectangular, trapezoidal or square cross section.
    Their surface will generally be between 1 and 7 mm 2 .
    These holes will be distributed, preferably regularly, with a density such that the total surface of the holes represents between 20 and 70%, and preferably between 30 and 60% of the total surface of the dressing.
    According to a preferred embodiment, the polymer matrix, when it is implemented in an interface dressing, preferably self-supporting, is in the form of an aerated net (or grid) preferably of square mesh having:
    - a thickness of the net between 0.4 and 2 mm;
    - a "wire width" (width of the space between two consecutive holes) between 1 and 10 mm, and preferably between 1 and 5 mm;
    - a grammage between 200 and 1700 g / m 2 , and preferably between 300 and 800 g / m 2 .
    According to a particularly preferred embodiment of the invention, such an elastomeric matrix will be in the form of an aerated square mesh net having:
    - a thickness of the net of approximately 750 microns;
    - a wire width (or mesh size) of the order of 0.8 mm;
    - a grammage of the order of 390 g / m 2 .
    For the production of such elastomeric matrices, reference may be made to patent application FR 2 936 158 for more details.
    It can also be envisaged to use this elastomeric matrix to coat a frame or a support.
    The techniques for manufacturing an interface dressing with reinforcement or with support are also well known to those skilled in the art and reference may for example be made to the methods described in patent applications WO 00 16725 and FR 2 936 159 or WO 2015/018720.
    Pad
    The subject of the invention is therefore, according to a preferred embodiment, an interface dressing characterized in that it comprises an elastomeric matrix previously described.
    According to an alternative embodiment, the present application aims to cover a self-supporting interface dressing comprising an elastomeric matrix in the form of a thin layer having through holes to allow the exudates to pass, obtained from a composition comprising:
    - 5 to 20% of at least one triblock copolymer of the styrene - saturated olefin styrene type,
    - 50 to 80% by weight of at least one plasticizer,
    - 0.5 to 15% of at least one alpha-methyl styrene type resin whose softening point is between 80 and 125 ° C, preferably between 90 and 110 ° C,
    0.1 to 15% of at least one active ingredient, the percentages being based on the total weight of the composition.
    Preferably, the interface dressing according to the present invention does not adhere to latex gloves. To do this, the composition may preferably comprise:
    - per 100 parts by weight of a mixture P of 2 specific triblock copolymers of the styrene - saturated olefin - styrene type, the first having a viscosity of between 0.01 and 1 Pa.s as measured in a 5% solution (mass / mass) in toluene and a second which has a viscosity between 0.01 and 0.5 Pa.s as measured in a 15% solution (mass / mass) in toluene;
    - from 300 to 1000 parts by weight of a plasticizer H, preferably a plasticizer oil; and
    - from 90 to 600 parts by weight of vaseline V;
    being further specified that:
    - The total amount, represented by P + H + V, of mixture of elastomers, plasticizer and petrolatum is between 490 and 1700 parts by weight;
    - The ratio between the total amount of the mixture of elastomers, the plasticizer and petroleum jelly and the quantity of petroleum jelly, represented by P + H + V / V, is less than 11;
    said mixture of 2 copolymers comprises at least 20% by weight of the first copolymer, the composition further comprising from 0.5 to 15% by weight of an alphamethyl styrene type resin whose softening point is between 80 and 125 ° C, preferably between 90 and 110 ° C, and 0.1 to 15% by weight of at least one active, the percentages being based on the total weight of the composition.
    In order to protect the composition from the external environment, the interface dressing may be covered, preferably on each of its faces, by a temporary protective film which will be removed before use by the user.
    In order to further facilitate the handling of the interface dressing, in particular if it is self-supporting, these two temporary protective films may be replaced by a single protector as described in patent application WO 2008/145 884 or in patent application WO2015 / 018720 whose particular structure facilitates the application of the dressing to the wound.
    figure
    The figure is a graphic representation of the dissolution profiles, evaluated as a percentage of active principle released relative to the amount contained in the mass from the dressings described in Example 1 and in Example 4.
    The present invention is illustrated in the nonlimiting examples presented below.
    EXAMPLES
    Preparation of the compositions
    The compositions of Examples 1 to 4 were prepared using the following constituents in the proportions, expressed as a percentage by weight, mentioned in Table 1 below.
    Elastomer: poly (styrene-ethylene-butylene-styrene) block copolymer (abbreviated SEBS):
    - KRATON® G 1651
    Plasticizer: Pionier 2076P mineral oil sold by Hansen & Rosenthal
    Vaseline: Codex® A vaseline sold by the company AIGLON
    Antioxidant: IRGANOX® 1010 sold by the company BASF
    Hydrocolloid: Carboxymethylcellulose sodium CMC BLANOSE® 7H4XF sold by the company ASHLAND,
    Resins: Sylvares SA 100, alpha-methyl styrene resin with a softening point between 95 and 105 ° C, sold by Arizona Chemical
    Active: Metformin from IPCA
    Composition manufacturing
    The carboxymethylcellulose, metformin and SEPINOV EMT 10 are premixed and sieved at 400 μm.
    Vaseline and oil are introduced into a mixer at a set temperature of 90 ° C, at a speed of 60 to 70 rotations per minute (rpm), then the powders of carboxymethylcellulose, SEPINOV EMT 10 and metformin are introduced. dim. We knead for 5 minutes.
    The set temperature is increased to 140 ° C. We then introduce the elastomer and the antioxidant. Mix for 45 minutes (until a smooth and homogeneous mixture is obtained). The resin is introduced 15 minutes before the end.
    It was then allowed to cool, and the mixer was drained.
    The compositions thus obtained were coated on a frame (marquisette 601 sold by the company MDB Texinov) according to the methods described in patent applications WO 00 16725 and FR 2 936 159 or WO 2015/018720
    Method of measurement of metformin release:
    Dissolution test procedure:
    Release kinetics of each active ingredient by the dissolutest method under the following conditions:
    - Device 6 according to USP, equipped with rotary cylinders
    -Stirring speed: 60 RPM
    - Medium temperature: 32.0 ° C ± 0.5 ° C
    -Middle :
    Physiological serum
    - Middle volume: 1000 mL
    - Medium sampling at TOh, 4h, 7h, 24h, 48h and 72h,
    - Dressing area: 100 cm 2
    The dressings are weighed before being placed on the cylinders.
    The results are expressed in% of active ingredient released, taking into account the theoretical quantity of each active ingredient in each dressing, ie:
    Actual mass of dressing x active content.
    The amount of active ingredient in each sample is determined by:
    HPLC / UV
    EQUIPMENT
    Luna SCX column 5 pm - 100 Â - 100 mm x 4.6 mm, ref. Phenomenex 00D-4398E0,
    HPLC system with UV detector, autosampler and column oven,
    REAGENTS
    Ammonium dihydrogen phosphate for analysis. For example: ref. VWR 21305.290 or equivalent,
    Low UV acetonitrile for analysis. For example: ref. VWR 20048.290 or equivalent,
    Sodium chloride for analysis. For example: ref. VWR 27810.295 or equivalent,
    Ultra pure water.
    REFERENCE SUBSTANCE
    Secondary reference metformin hydrochloride kept in a closed bottle stored in a desiccation cabinet.
    SOLUTIONS / SAMPLES TO PREPARE
    Mobile phase
    The mobile phase is a 17 g / L ammonium dihydrogen phosphate solution to which 2% acetonitrile is added.
    Test solutions
    Preliminary precaution: the physiological saline used during the analysis will be previously thermostatically controlled at 32 ° C.
    OPERATING CONDITIONS
    Table 1: Chromatographic conditions
    Column Luna SCX - 5 pm - 100 mm x 4.6 mm Mobile phase Ammonium dihydrogen phosphate at 17 g / L +2% acetonitrile Debit 1.2 mL / min Sample changer temperature Unrefrigerated and not temperature monitored Subdivision temperature atcolumn 35 ° C Fashion isocratic Injection volume 10 pL Detection UV set to 232 nm Mcllormin peak retention time About 6 minutes Analysis time 10 minutes
    Report results
    All the results will be reported in summary tables such as those described above, then the release kinetics of metformin are plotted as a function of time (expressed in hours).
    Examples 1 to 4
    Ex.l Ex. 2 Ex.3 Ex. 4 Ref. commercial % weight % weight % weight % weight SEBS (Kraton G1651 ES from KratonPolymer) 4.9 4.9 4.9 4.9 White mineral oil (Pionier 2076P) 69.8 67.8 60.2 49.8 Carboxymethyl cellulose sodium (CMCBlanose 7H4XF from Aschland) 15.0 15.0 15.0 15.0 T etrakis3 - (3,5 -di-tert-butyl-4hydroxyphenyl) pentacrythitol propionate (BASF Irganox 1010) 0.2 0.2 0.2 0.2 Vaseline (Vaseline Codex A from Synteal) 5.0 5.0 5.0 5.0 alpha methylstyrene resin with a softening point between 95 and 105 ° C Sylvares SA 100 0 2.0 9.6 20 copolymer of the salt of 2-methyl-2 [(loxo-2-propenyl) amino] -1 propanesulfonic acid and the 2-hydroxyethyl ester of propenoic acid (Sepinov EMT 10 from SEPPIC) 0.1 0.1 0.1 0.1 Metformin IPCA 5.0 5.0 5.0 5.0 Marquisette 601 601 601 601
    Table 3: metformin release in percentage released compared to the quantity contained in the mass
    Cumulative average release in percentage Examples h 4 7h 24 48h 72h Example 133 35 46 59 67 Example 235 38 52 68 78 Example 337 40 57 74 85 Example 425 30 45 58 71
    It is therefore found that at 2% and 9.6% by weight, the alpha methylstyrene resin makes it possible to increase the percentage of active ingredient released. When we put 20% of said resin, we find roughly the same proportions of released assets as when the composition does not include resin.
    权利要求:
    Claims (13)
    [1" id="c-fr-0001]
    1. Composition including:
    - 5 to 20% by weight of at least one triblock copolymer of the ABA type, comprising two thermoplastic end blocks A styrene and a central elastomer block B which is a saturated olefin or of a mixture of triblock copolymers of the ABA type, comprising two thermoplastic terminal blocks A styrene and an elastomer central block B which is a saturated olefin, based on the total weight of the composition
    - 50 to 80% by weight of at least one plasticizer,
    - 0.5 to 15% by weight of an alpha methylstyrene resin with a softening point between 80 and 125 ° C, preferably between 90 and 110 ° C
    - 0.1 to 15% of an active ingredient, the percentages being based on the total weight of the composition.
    [2" id="c-fr-0002]
    2. Composition according to claim 1, characterized in that the plasticizer consists of a mixture of mineral oil and petrolatum.
    [3" id="c-fr-0003]
    3. Composition according to one of the preceding claims, characterized in that it comprises hydrocolloid particles in an amount less than or equal to 25% by weight, based on the total weight of the composition.
    [4" id="c-fr-0004]
    4. Composition according to one of the preceding claims, characterized in that the active agent is chosen from agents promoting healing, antibacterial agents, antiseptics, painkillers, local anesthetics or anti-inflammatories, and preferably among the agents promoting healing.
    [5" id="c-fr-0005]
    5. Composition according to the preceding claim, characterized in that the agent promoting healing is chosen from agents promoting healing, retinol, vitamin A, vitamin E, N-Acetyl Hydroxyproline, extracts of Centella Asiatica, papain, silicone, essential oils of thyme, niaouli, rosemary, sage, hyaluronic acid, sucrose potassium octasulfate, sucralfate, allantoin, metformin, and preferably, the agent promoting healing is metformin.
    [6" id="c-fr-0006]
    6. Elastomeric matrix, characterized in that it is obtained from a composition according to one of claims 1 to 5, preferably by formation of a thin layer and compression, or by hot casting of said composition on a support or a frame.
    [7" id="c-fr-0007]
    7. Elastomeric matrix according to claim 6, characterized in that it comprises a frame or a support, or in that it is self-supporting.
    [8" id="c-fr-0008]
    8. Self-supporting elastomeric matrix according to claim 7, characterized in that it has through holes.
    [9" id="c-fr-0009]
    9. Self-supporting elastomeric matrix according to one of claims 7 or 8, characterized in that it is in the form of an aerated net whose mesh size is
    5 on the order of 4 mm 2 , the thickness on the order of 800 microns and the grammage on the order of 400 g / m 2 .
    [10" id="c-fr-0010]
    10. Interface dressing, characterized in that it comprises an elastomeric matrix according to one of claims 6 to 9.
    [11" id="c-fr-0011]
    11. Use of an alpha-methyl styrene type resin to promote
    10 release of active ingredient in a composition, in particular used in a dressing.
    [12" id="c-fr-0012]
    12. Use according to claim 11, characterized in that the resin of the alpha-methyl styrene type has a softening point situated between 80 and 125 ° C, preferably between 90 and 110 ° C.
    [13" id="c-fr-0013]
    13. Use according to one of the preceding claims, characterized in that the active agent is chosen from agents promoting healing, antibacterial agents, antiseptics, painkillers, local anesthetics or anti-inflammatories.
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    同族专利:
    公开号 | 公开日
    WO2019012229A1|2019-01-17|
    CN110868970A|2020-03-06|
    US20200129654A1|2020-04-30|
    FR3068974B1|2019-08-02|
    EP3651706A1|2020-05-20|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US20020128345A1|2000-12-29|2002-09-12|Paul Charles W.|Hot melt adhesives for dermal application|
    US20100285129A1|2007-05-25|2010-11-11|Laboratoires Urgo|Novel agent for salting out active principles in dressings containing at least one of fatty substance|
    US20150174285A1|2012-07-17|2015-06-25|Laboratories Urgo|Self-supporting interface dressing|
    WO2016097653A1|2014-12-19|2016-06-23|Laboratoires Urgo|Dressing comprising a support and a hydrophobic elastomeric matrix|
    FR2783412B1|1998-09-18|2000-12-15|Lhd Lab Hygiene Dietetique|NON-ADHERENT STERILE COMPRESS|
    JP2001181591A|1999-12-28|2001-07-03|Nitto Denko Corp|Block copolymer adhesive and medical adhesive tape and percutaneous absorption pharmaceutical preparation using this and preparation method of block copolymer adhesive|
    FR2806629B1|2000-03-22|2003-01-24|Lhd Lab Hygiene Dietetique|ANTISEPTIC COMPRESS|
    FR2809310B1|2000-05-26|2004-02-13|Centre Nat Rech Scient|USE OF BIGUANIDE DERIVATIVES FOR MANUFACTURING A MEDICINAL PRODUCT HAVING A HEALING EFFECT|
    FR2914847B1|2007-04-13|2009-07-10|Urgo Soc Par Actions Simplifie|NEW PROTECTOR FOR DRESSINGS|
    EP1985290A1|2007-04-26|2008-10-29|Sansho Cosme Inc.|Skin application medicament, method of applying the same to skin and method of manufacturing the same|
    FR2936159B1|2008-09-24|2010-10-22|Plasto|SURGICAL INTERFACE FOR WOUND, WITH SUPPORT|
    FR2936158A1|2008-09-24|2010-03-26|Plasto|SURGICAL INTERFACE FOR WOUND, WITHOUT SUPPORT|
    FR2974004B1|2011-04-15|2014-05-02|Urgo Lab|HYDROCELLULAR ABSORBENT DRESSING, ITS USES FOR THE TREATMENT OF CHRONIC AND ACUTE WOUNDS|
    CN102850710B|2012-08-21|2013-10-16|侯玉庆|Framework material for medical plaster and preparation method thereof|
    FR3009188B1|2013-08-05|2017-02-17|Urgo Lab|INTERFACE BANDING APPLICATOR DEVICE|GB201020236D0|2010-11-30|2011-01-12|Convatec Technologies Inc|A composition for detecting biofilms on viable tissues|
    EP2648793B1|2010-12-08|2020-03-11|ConvaTec Technologies Inc.|Integrated system for assessing wound exudates|
    ES2748519T3|2010-12-08|2020-03-17|Convatec Technologies Inc|Wound exudate system accessory|
    GB2497406A|2011-11-29|2013-06-12|Webtec Converting Llc|Dressing with a perforated binder layer|
    WO2018009873A1|2016-07-08|2018-01-11|Convatec Technologies Inc.|Fluid collection apparatus|
    法律状态:
    2018-07-27| PLFP| Fee payment|Year of fee payment: 2 |
    2019-01-18| PLSC| Search report ready|Effective date: 20190118 |
    2019-07-29| PLFP| Fee payment|Year of fee payment: 3 |
    2020-07-27| PLFP| Fee payment|Year of fee payment: 4 |
    2021-07-26| PLFP| Fee payment|Year of fee payment: 5 |
    优先权:
    申请号 | 申请日 | 专利标题
    FR1756590|2017-07-12|
    FR1756590A|FR3068974B1|2017-07-12|2017-07-12|DRESSING FOR THE CONTROLLED AND PROLONGED DELIVERY OF ASSETS|FR1756590A| FR3068974B1|2017-07-12|2017-07-12|DRESSING FOR THE CONTROLLED AND PROLONGED DELIVERY OF ASSETS|
    CN201880046157.4A| CN110868970A|2017-07-12|2018-07-12|Controlled and sustained release dressing for metformin|
    US16/629,132| US20200129654A1|2017-07-12|2018-07-12|Dressing Providing for the Controlled and Sustained Release of Metformin|
    PCT/FR2018/051758| WO2019012229A1|2017-07-12|2018-07-12|Dressing providing for the controlled and sustained release of metformin|
    EP18749036.2A| EP3651706A1|2017-07-12|2018-07-12|Dressing providing for the controlled and sustained release of metformin|
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