FR2875412A1 - Material, useful to obtain a medicated device and for local/topical treatment, comprises: a textile support; a multiplicity of microcapsules; and an envelope comprising a second material of polymer type - Google Patents

Abstract

Material (A) for local/topical treatment, comprising fibers and/or threads (2, 3), and/or filaments of a primary material, comprises: a textile support (4) comprising an internal side (4a) for contacting with a surface part of human body; a multiplicity of microcapsules (5) distributed and supported by the textile support (where each microcapsule comprises a liquid core (6)); and an envelope (7) comprising a second material of polymer type. Material (A) for local or topical treatment, comprising fibers and/or threads (2, 3), and/or filaments of a primary material of the knit or non woven fabric type, comprises: a textile support (4) comprising an internal side (4a) for contacting with a surface part of the human body (where the textile support is permeable in its thickness compared to the passage of a liquid/gas or an ionized flow); a multiplicity of microcapsules (5) distributed and supported by the textile support (where each microcapsule comprises a liquid core (6), in which at least an active ingredient is topically distributed); and an envelope (7) comprising a second material of polymer type (which is tight when compared to the liquid core) (where: the liquid core of the microcapsules are hydrophobic/lipophilic; the second material allows the passage of the liquid core supporting the active ingredient by diffusion in solid state and under low thickness; and the primary material in contact with second material allows the direct contact of the microcapsules on the textile support). Independent claims are also included for: a piece for topical treatment, comprising obtained shaping or finishing of a material; and device - orthetic, prosthetic, or orthopedic, comprising a piece.

Description

The present invention relates, in general, to any treatment

  topical or local human body, and in particular by means of a textile support, fabric type, knitted or non-woven, integrated or not in a part or device of the type orthotic, prosthetic, or orthopedic.

  A compression stocking comprising or consisting of a topical treatment material has already been described and proposed. The latter consists, on the one hand, of a textile support, of the fabric or knit type, comprising threads and / or filaments of a first material, having an inner face intended to come into contact with a superficial part of the body human, this textile support being permeable in its thickness relative to the passage of a gas or a liquid, and secondly, by a plurality of microcapsules distributed and supported by the textile support, each microcapsule comprising, of a side, a liquid heart in which at least one active ingredient is dispensed topically, and on the other side, an envelope comprising a second material of the polymer type, sealed with respect to said liquid core, that is to say enclosing and retaining said liquid core, the microcapsules being fixed on the textile support by an adhesive-type binder.

  With the topical treatment material described above, the mechanical force exerted on the microcapsules, when the compression stocking is worn, or when wearing it on the patient's leg, for example, causes the microcapsules to rupture and the release in contact with the skin of the active ingredient topically supported by the liquid heart.

  This results in an almost immediate release of the active ingredient, then acting locally, for example topically, and possibly systemically.

  For many treatments, for example therapeutic, this almost immediate release of the active ingredient results in an instantaneous treatment, but not durable, in any case that does not extend over time.

  However, it appears desirable, for many treatments, to prolong in time the beneficial effect, for example biological, of the active ingredient topically.

  The present invention therefore relates, for a material as described above, a solution for controlled release of the active ingredient locally.

  According to the present invention, the system "textile support / microcapsules" is approached from the angle of the materials constituting it, distinguishing in particular the first material constituting the fibers and / or threads and / or filaments of the textile support, and the second material of the envelope of microcapsules.

  And a controlled release mode of the active ingredient is obtained by the combination of the following parameters, namely: by a suitable choice of the first (textile support) and the second (envelope of microcapsules) materials, virtually any binder 10 is eliminated between the microcapsules and the textile support, by direct contact with each other, - the liquid core of the microcapsules is hydrophobic or lipophilic, - and the second material (envelope microcapsules) allows, in the solid state and in small thickness, the diffusion passage to the skin of the liquid heart supporting the active ingredient topically.

  The technical choices of the present invention are shown by the appended drawing, in which: FIG. 1 is a schematic side sectional view of a local or topical treatment material according to the present invention, FIG. enlarged scale, a detail of this material.

  A local or topical treatment material 1 according to the invention, in contact with a surface portion 8 of the human body, is shown in FIGS. 1 and 2.

  This material 1 comprises: - a textile support 4, for example a fabric constituted by warp threads 2 and weft threads 3, having an inner face 4a intended to come into contact with a surface portion 8 of the human body; this textile support consists of a first material, and is permeable according to its thickness relative to the passage of a liquid or a gas or an ionized flux, - a multiplicity of microcapsules 5 distributed and supported by the textile support, each microcapsule comprising a liquid core 6 in which at least one active ingredient is distributed locally or topically, and an envelope 7 comprising a second material of the polymer type, sealed with respect to the liquid core, subject to the diffusion or progressive permeation of the liquid core supporting the active ingredient, the liquid core 6 of the microcapsules 5 is hydrophobic or lipophilic; the second material, that is to say that of the envelope 7 of the microcapsules, allows the solid state and under a small thickness passage diffusion of the liquid core 6 supporting the active principle; and the first material, that is to say that of the textile support 4, allows the direct connection of the microcapsules on said textile support.

  By "textile support" is generally meant any entanglement, ordered or not, of fibers, and / or filaments and / or yarns of at least one material of textile nature, hereinafter referred to as "first material", by difference with respect to the "second material" constituting the envelope of the microcapsules, as indicated below.

  This textile support has a certain permeability with respect to the passage according to its thickness, low (two-dimensional textile), or strong (three-dimensional textile) of any fluid, liquid or gas, which implies that this support has a structure, texture, or porous construction or airy.

  This textile support is first of all, for example, a nonwoven consisting of the disordered entanglement of discontinuous fibers and / or filaments of the first material.

  The permeability required for the textile support is at least that permitting, for example, the passage along its thickness of any liquid phase in which the microcapsules are distributed and suspended, and for the purpose of putting in direct contact the fibers and / or son and / or filaments of the textile support with the microcapsules. This permeability can also allow the passage of air and moisture, when the material according to the invention is in contact with the skin.

  This textile support is then, for example, an ordered arrangement of son, themselves made of continuous filaments or staple fibers of the first material, in which case it is a fabric, which can be defined for example by its armor and its texture, or a knit that can be defined by its armor and the configuration of the knitting machine to obtain it.

  The term "textile support" is intended to cover also materials of the paper type, very close in particular nonwovens.

  Classically, the first material, constituting the textile support, comprises a natural material, of plant origin (for example cotton, linen) or of animal origin (for example silk, wool) and / or a synthetic material ( for example a polyamide, a polyester, polypropylene).

  Furthermore, the textile support according to the invention may have received one or more complementary treatments, in particular with a view to the direct attachment of the microcapsules, during its impregnation with a liquid phase, for example an aqueous phase, in which the microcapsules are distributed and suspended.

  Two nonwovens have been tested below according to the present invention: viscose / water-jet-bonded polyester (Jacob Holm), viscose / needled-calendered polyester (Orsa), polypropylene meltblown (BBA).

  Two fabrics have also been tested according to the invention: - polyester microfiber cloth, - polyester cotton twill.

  The textile supports thus chosen have the advantage of being easily usable according to the methods of application of the microcapsules retained (by suction). They can be placed inside knee pad or lumbar belt. They can be replaced by any other tight support (fabric, non-woven material of low porosity).

  By "microcapsules" is meant entities obtained according to any well known per se technique of encapsulation, for example by emulsion-evaporation of a solvent or inter-facial polycondensation.

  Each microcapsule is a particle of substantially spherical shape, whose average diameter is between 1 m and 1000 m, and preferably between 20 and 300 m, and for example between 10 and m. Each microcapsule comprises an inner core or core, constituted according to the present invention by a continuous liquid phase, hydrophobic or lipophilic, in which is distributed, in suspension or solution, the active ingredient topically or locally. This internal liquid core is enclosed by an outer shell or membrane comprising according to the present invention the material, called "second material", based on one or more polymers. According to the present invention, the second material is chosen or formulated to allow over time the diffusion or permeation of the liquid heart supporting the active ingredient topically.

  The continuous liquid phase, hydrophobic or lipophilic, of the core is, for example, benzyl benzoate, a mixture of esters, for example sold under the name Miglyol by the company SASOL, or else vitamin E. The second constituent material of the The envelope of the microcapsules is, for example, a polyacrylate, for example polymethyl methacrylate, or else, for example, that sold under the name Eudragit® manufactured by ROHM and marketed by SPCI, or else ethylcellulose with the trade name AQUALON ETHYLCELLULOSE N 22 supplied by SPCI.

  Microcapsules are distinguished from microspheres which are matrix systems in which the active ingredient is dispersed in a polymer matrix.

  By "active ingredient locally or topically" is meant any substance, compound, or composition exerting a beneficial action, for example biological or medicinal, due to its contact with a superficial part of the human body.

  This beneficial action is first, for example, medicinal, topically, locally and / or systemically. And in such a case, the active principle will be chosen in the major pharmaco-therapeutic classes, among which may be mentioned, for example, non-steroidal anti-inflammatory drugs (for example Ibuprofen O), muscle relaxants, topical corticosteroids, topical medicinal products, etc. phlebology, surface anesthetics, antibiotics, antivirals, antifungals, antiseptics and antihistamines.

  This beneficial action is then of a cosmetic order, or of the order of well-being. And in such a case, the active ingredient is, for example, a moisturizing, lubricating or antibacterial substance.

  Of course, the active ingredient requires a vehicle, for example excipient, for its support or transport to the treated surface of the human body.

  In practice, according to the present invention, this role is played by the liquid heart of the microcapsules, of hydrophobic or lipophilic nature, which is opposed for example to the hydrophilic nature of the second material, that is to say that of the envelope microcapsules.

  The present invention also presents, in a preferred manner, the following embodiments: the microcapsules are distributed on the internal face and / or in the thickness of the textile support, the material according to the invention is capable of being obtained by impregnation and / or passage in the textile support of a liquid phase, for example an aqueous phase, in which the microcapsules are distributed and suspended, - the material according to the invention can be obtained by treatment of the textile support with a liquid phase in which the microcapsules are suspended, of the padding, impregnation, filtration, priming, spraying, coating, transfer or laminating type, the textile support is elastic or rigid according to at least one dimension of said material, the second material comprises an agent surfactant, for example used for obtaining microcapsules, promoting or increasing the adhesion of said microcapsules on the son e and / or filaments of the textile support, the surfactant is a hydrolysed polyvinylacetate, the microcapsules can be obtained by emulsion-evaporation of a solvent, or interfacial polycondensation, the microcapsules have a diameter of between 1 m and 1000 m, and preferably between 20 m and 300 m, the second material comprises a polymer for use as a pharmaceutical excipient, for example polymethacrylate, and / or a polyamide, microcapsules comprising an envelope made of a second material of the type polymethacrylate, and microcapsules comprising a casing made of a second material of the polyamide type are distributed and supported, in a mixture, on the textile support, the part can be obtained by shaping or work of a material as previously defined.

  The invention further relates to any use of a material as defined above for obtaining a drug device, ie for the topical administration of a medicament.

  The invention also relates to any piece of topical treatment, obtainable by shaping or work of a material as defined above.

  The invention finally relates to any orthotic, prosthetic or orthopedic device comprising such a part; such a device may comprise, by way of example a flexible piece, and a topical treatment piece disposed on the inside of the flexible piece, with its internal face against the skin.

  By "orthotic device" is generally meant any device arranged to supplement or correct a deficient function, or to compensate for the limitations or even increase the physiological performance of an organ or limb of the human body, which has lost its function, which has never developed well, or has congenital anomalies. In particular, it is an external device or device used to modify the structural or functional conditions of the neuromuscular or skeletal system (cf standard NF-150-8549 01/05/1990).

  The orthotic or orthotic devices according to the present invention are used: for a medical and / or paramedical purpose (analgesic, cicatrization, compensation, stabilization, correction, venotonic), in the field of high level sport (example of function: preventive action) , post-operative protection, sports recovery after trauma), - for comfort or well-being (eg thermotherapy).

  The orthosis may be composed of an elastic knit which provides compression and which may be reinforced by rigid parts comprising a topical treatment material according to the invention, providing the desired medicinal function and good contact with the skin.

  The orthotic medical devices (or orthoses) according to the invention are used in rheumatology, traumatology and phlebology. The following experimental protocol was implemented.

  Test No. 1: Microcapsules Obtained by the Method of Emulsion Evaporation of Solvent

  According to this method, two solutions called respectively A and B form a dispersed phase: the solution A contains the second material, ie that constituting the envelope of the microcapsules, and a solvent of said second material, for example dichloromethane or chloroform, solution B contains the liquid phase, hydrophobic or lipophilic, constitutive of the core of the microcapsules, and the active ingredient soluble in this liquid phase, for example a non-steroidal anti-inflammatory drug such as ibuprofen; in such a case, said liquid phase of solution B is soluble in the solvent of solution A, but insoluble in the continuous phase defined below.

  The continuous phase is an aqueous phase in which a surfactant is added, for example an aqueous solution of hydrolysed vinyl polyacetate (PVA).

  An emulsion is formed between the dispersed and continuous phases previously defined. Then the solvent of the dispersed phase evaporates, whereby microcapsules comprising an envelope in the second material are obtained, with a core of the liquid phase, hydrophobic or lipophilic, supporting the active principle.

  For more details on this method by emulsion-evaporation of solvent, reference is made in particular to the following works: Microspheres, Microcapsules and Liposomes, Reza Arshady, Volume 1, R. Arshady Editor, Citus Book page 296.

  Two tests according to the preceding method are carried out: Test No. 1. The solvents used for the formation of the microcapsules are benzyl benzoate, Miglyol 812 and vitamin E. These solvents solubilize the active ingredient to be encapsulated, they are insoluble in the water. water and are accepted by the pharmacopoeia.

  The surfactant used for the continuous aqueous phase, 88% hydrolysed polyvinyl acetate (polyvinyl alcohol or PVA) has an HLB (hydrophilic-hydrophobic balance) of between 10 and 17.

  The surfactant used is well suited for the stabilization of oil-in-water emulsions. The necessary criterion is HLB (hydrophilic-hydrophobic balance): <HLB <17.

  The active ingredient to be encapsulated is ibuprofen, or 2- (4isobutylphenyl) propanoic acid.

  An example of an operating procedure is described below: The dispersed phase is composed of two solutions: solution A and solution B Solution A: 4 g Eudragit RS PO + 80 ml of dichloromethane - solution B: 4 g of Miglyol 812 + 1 g of ilbuprofen or 4 g of vitamin E + 1 g of ibuprofen or 4 g of benzyl benzoate + 0.6 g of ibuprofen After magnetic stirring of the mixture of solution A and solution B until complete dissolution the dispersed phase is obtained.

  The continuous phase consists of 800 ml of an aqueous solution of PVA (88% hydrolyzed).

  Test No. 1.2 The operating procedure is different in the case of the formulation of microcapsules of poly (methyl methacrylate).

  The dispersed phase is composed of two solutions A and B as previously described: Solution A: 0, 8 g of PMMA + 20 ml of dichloromethane, Solution B: 1 g of benzyl benzoate + 0.05 mg of ibuprofen .

  The continuous phase consists of 200 ml of aqueous solution of poly (vinyl alcohol) hydrolyzed to 88% at a concentration of 4% relative to the aqueous phase.

  The process is identical to that described previously.

  Test No. 2: Microcapsules Obtained by the Interfacial Polycondensation Method.

  According to this method, the liquid phase, hydrophobic or lipophilic, of the microcapsules constitutes a dispersed phase in which are solubilized, and a part of the monomers, for example acid chlorides, forming the second material, for example polyamide, after polymerization, and the active ingredient. And a continuous aqueous phase, for example an aqueous solution of PVA, dissolves the other part of the monomers, for example polyamides constituting the second material.

  From an emulsion of the dispersed phase in the continuous phase, a polycondensation reaction develops at the interface between the dispersed phase and the continuous phase, and leads to the formation of envelopes of the second polyamide material microencapsulating a liquid core. hydrophobic or lipophilic, supporting the active principle.

  For more details on this method by interfacial polycondensation, reference will be made in particular to the same work as mentioned above, see page 292.

  The following test is then conducted: The dispersed phase is composed of 30 ml of Miglyol 812 and the continuous phase of 300 ml of aqueous PVA solution. The acid chloride monomers are solubilized in the dispersed phase as well as the active ingredient, and the amine monomers in the aqueous phase: - amines: hexamethylenediamine 4.48 g + diethylenetriamine 2. 63 g - acid chloride: sebacoyl chloride 3 g + trimesoyl chloride 0.37 g 20% (mol) of the amines reacted, 100% of the acid chlorides are consumed.

  According to tests 1.1 and 1.2, Eudragit microcapsules having a diameter of between 20 and 60 microns enclosing lbuprofen are obtained. After contacting with a textile support as defined above, according to the impregnation protocol defined according to test No. 3, these microcapsules adhere well to the treated surfaces, including during manual rinsing, but giving a tacky feel.

  According to test 2, polyamide microcapsules having a diameter of between 60 and 600 microns, enclosing Ibuprofen O, are obtained. After contacting with a textile support as defined above, and according to the impregnation protocol according to In test 3, these microcapsules remain in contact with the treated surfaces, giving it a pleasant soft feel, but they can be eliminated by manual rinsing.

  Test No. 3: Using polyacrylate microcapsules (Eudragit for example) and polyamide microcapsules, it is possible to marry the role of binder of the former and the role of mechanical reinforcement of seconds.

  To this end, for the purposes of impregnating a textile support defined below, 2 ml of a suspension n 1 of crosslinked polyamide microcapsules (second material), and 10 ml of a suspension of microcapsules of polyacrylate (Eudragit, second material) are prepared, then mixed according to the compositions and then mixed, according to Tables 1 and 2 below.

  Table 1: composition of the suspension Suspensions Second ô Liquid phase Water Conc.en Ibu / suspension material v hydrophobic (g) Conc. in Ibu / MS Nature and content in MS / susepnsion mass (g) Suspension Polyamide 3, 7 Miglyol 812 300 12, 33 g / 1 n 1 crosslinked 30 ml 9.85% 4.4 29.4 g 12.5% Suspension Eudragit 1 Miglyol 812 800 1.25 g / 1 n 2 4 4g 11.11% 1.12% Table 2: Ibuprofen concentrations O Ibu content in the susp (g / I) c L, o E.-.

  c Ibu content in the MS 5%) o> c <D C7 Q. Content of the MS in the susp (%) -coreceptin C n 12.33 g / l 12.33 mg of lbu 2 ml 24.7 250 9.85% 125 mg of MS 12.5 0/0 N 2 1.25 g / 1 1.25 mg of lbu 10 ml 12.5 125 11.11% 12.5 mg of MS 1.12% Suspension 12 ml 37.2 375 final Then 12 ml of the final suspension obtained are filtered through a test-tube of a textile support according to Table 3. Table 3: Characteristic of the test pieces obtained Textile support Non-woven viscose / needle-punched polyester calendar (Orsa) Ibu content in the MS of the suspension 10.5% final External diameter of the test specimen disc 50 mm Internal diameter of the specimen disc 35 mm External surface of the specimen disc 1963.5 mm2 Internal surface of the specimen disc 962, 1 mm2 surfaces 2.04 Average mass of discs 283.9 mg test pieces Average mass of sample disc 139.2 mg effectively processed Average surface density of discs 144.6 g / m2 or 0.1466 mg / mm2 test pieces treated Average dry matter content 62.4% or 62.4 mg DM for 37.6 mg of treated fibers, ie 260 mm2 or 0.24 mg / mm2 Average contents of DM per mm2 0.24 mg / mm 2 or 24 mg / cm 2 Average levels of Ibu per mm 2 2.21 mg / cm 2 In this example, the ibuprofen 0 (nonsteroidal anti-inflammatory) level is 2.21 mg ibuprofen per cm2 of textile surface.

  According to the observations made by scanning electron microscopy, the distribution of the polyamide and Eudragit capsules on the polyester viscose nonwoven is uniform over the entire treated surface of the disc.

  When rinsing under tap water, the microcapsules on the nonwoven polyester viscose support are observed to hold well during manual rinsing with cold water.

  The touch of the materials obtained is soft and pleasant.

Claims (15)

  1. Material (1) of local or topical treatment consisting of fibers, and / or yarns (2, 3), and / or filaments of a first material, of the fabric, knit, or nonwoven type comprising, on the one hand, a textile support (4) having an inner face (4a) intended to come into contact with a superficial part of the human body, said textile support being permeable in its thickness with respect to the passage of a liquid or a gas, or an ionized flux, and on the other hand, a plurality of microcapsules (5) distributed and supported by said textile support, each microcapsule comprising a liquid core (6) in which at least one active ingredient is distributed by topically, and an envelope (7) comprising a second material of the polymer type, sealed with respect to said liquid core, characterized in that the liquid core (6) of the microcapsules (9) is hydrophobic or lipophilic, the second material allows the solid state and under thin the passage by diffusion of the liquid core (6) supporting the active principle, and the first material in contact with the second material allows the direct connection of the microcapsules on the textile support (4).   2. Material according to claim 1, characterized in that the microcapsules are distributed on the inner face and / or in the thickness of the textile support.   3. Material according to claim 1, characterized in that it is obtainable by impregnation and / or passage in the textile support of a liquid phase, for example aqueous, in which the microcapsules are distributed and suspended.   4. Material according to claim 3, characterized in that it is obtainable by treatment of the textile support with a liquid phase in which the microcapsules are suspended, pad-like type, impregnation, filtration, priming, spraying, coating, transfer or lamination.   5. Material according to claim 1, characterized in that the textile support is elastic or rigid in at least one dimension of said material.   6. Material according to claim 1, characterized in that the second material comprises a surfactant, for example used for obtaining microcapsules, promoting or increasing the attachment of said microcapsules on the son and / or filaments of the textile support .   7. Material according to claim 6, characterized in that the surfactant is a hydrolysed polyvinyl acetate.   8. Material according to claim 1, characterized in that the microcapsules are capable of being obtained by emulsion-evaporation of a solvent, or interfacial polycondensation 9. Material according to claim 1, characterized in that the microcapsules have a diameter of between 1 m and 1000 m, and preferably between 10 and 100 m.   10. Material according to claim 1, characterized in that the second material comprises a polymer for use as a pharmaceutical excipient, for example polymethacrylate, or a polyamide.   11. The material as claimed in claim 1, characterized in that microcapsules comprising an envelope made of a second material of the polymethacrylate type, and microcapsules comprising an envelope made of a second material of the polyamide type, are distributed and supported, in a mixture, on the support. textile.   12. Topical treatment room, characterized in that it is obtainable by shaping or work of a material according to any one of claims 1 to 11.   13. Orthotic, prosthetic or orthopedic device, characterized in that it comprises a part according to claim 12.   14. Device according to claim 13, characterized in that it comprises a flexible piece, and the topical treatment piece is disposed on the inner side of the flexible piece, with its inner face against the skin.   15. Use of a material according to any one of claims 1 to 11, for obtaining a drug device.