EP3484532A1 - Dressing enabling the controlled and prolonged release of metformin - Google Patents
Dressing enabling the controlled and prolonged release of metforminInfo
- Publication number
- EP3484532A1 EP3484532A1 EP17751436.1A EP17751436A EP3484532A1 EP 3484532 A1 EP3484532 A1 EP 3484532A1 EP 17751436 A EP17751436 A EP 17751436A EP 3484532 A1 EP3484532 A1 EP 3484532A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- metformin
- matrix
- weight
- dressing
- relative
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
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- 239000007921 spray Substances 0.000 description 1
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- MNQYNQBOVCBZIQ-JQOFMKNESA-A sucralfate Chemical compound O[Al](O)OS(=O)(=O)O[C@@H]1[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](COS(=O)(=O)O[Al](O)O)O[C@H]1O[C@@]1(COS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)O1 MNQYNQBOVCBZIQ-JQOFMKNESA-A 0.000 description 1
- 229960004291 sucralfate Drugs 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000004583 superabsorbent polymers (SAPs) Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
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- 229960002871 tenoxicam Drugs 0.000 description 1
- WZWYJBNHTWCXIM-UHFFFAOYSA-N tenoxicam Chemical compound O=C1C=2SC=CC=2S(=O)(=O)N(C)C1=C(O)NC1=CC=CC=N1 WZWYJBNHTWCXIM-UHFFFAOYSA-N 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229940040944 tetracyclines Drugs 0.000 description 1
- 239000004753 textile Substances 0.000 description 1
- 229920001169 thermoplastic Polymers 0.000 description 1
- 239000004416 thermosoftening plastic Substances 0.000 description 1
- 229960000790 thymol Drugs 0.000 description 1
- 239000001585 thymus vulgaris Substances 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- 229910052719 titanium Inorganic materials 0.000 description 1
- 229960004380 tramadol Drugs 0.000 description 1
- TVYLLZQTGLZFBW-GOEBONIOSA-N tramadol Natural products COC1=CC=CC([C@@]2(O)[C@@H](CCCC2)CN(C)C)=C1 TVYLLZQTGLZFBW-GOEBONIOSA-N 0.000 description 1
- 150000003648 triterpenes Chemical class 0.000 description 1
- 229960002004 valdecoxib Drugs 0.000 description 1
- LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
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- BOXSVZNGTQTENJ-UHFFFAOYSA-L zinc dibutyldithiocarbamate Chemical compound [Zn+2].CCCCN(C([S-])=S)CCCC.CCCCN(C([S-])=S)CCCC BOXSVZNGTQTENJ-UHFFFAOYSA-L 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/44—Medicaments
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/24—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/22—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons containing macromolecular materials
- A61L15/34—Oils, fats, waxes or natural resins
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L1/00—Compositions of cellulose, modified cellulose or cellulose derivatives
- C08L1/08—Cellulose derivatives
- C08L1/26—Cellulose ethers
- C08L1/28—Alkyl ethers
- C08L1/286—Alkyl ethers substituted with acid radicals, e.g. carboxymethyl cellulose [CMC]
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L53/00—Compositions of block copolymers containing at least one sequence of a polymer obtained by reactions only involving carbon-to-carbon unsaturated bonds; Compositions of derivatives of such polymers
- C08L53/02—Compositions of block copolymers containing at least one sequence of a polymer obtained by reactions only involving carbon-to-carbon unsaturated bonds; Compositions of derivatives of such polymers of vinyl-aromatic monomers and conjugated dienes
- C08L53/025—Compositions of block copolymers containing at least one sequence of a polymer obtained by reactions only involving carbon-to-carbon unsaturated bonds; Compositions of derivatives of such polymers of vinyl-aromatic monomers and conjugated dienes modified
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L9/00—Compositions of homopolymers or copolymers of conjugated diene hydrocarbons
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L91/00—Compositions of oils, fats or waxes; Compositions of derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L91/00—Compositions of oils, fats or waxes; Compositions of derivatives thereof
- C08L91/06—Waxes
- C08L91/08—Mineral waxes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
- A61L2300/204—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
- A61L2300/206—Biguanides, e.g. chlorohexidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L2203/00—Applications
- C08L2203/02—Applications for biomedical use
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L2205/00—Polymer mixtures characterised by other features
- C08L2205/02—Polymer mixtures characterised by other features containing two or more polymers of the same C08L -group
Definitions
- the present invention relates to a dressing for the controlled and prolonged release of metformin.
- Wound healing usually depends on the proliferation of new epithelial, endothelial and connective tissues. It therefore involves 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 only take place if the previous step ends. This is a complex process that is underpinned by successive waves of growth factors and inflammatory mediators.
- the pharmaceutical market currently offers many recommended topical preparations to promote wound healing.
- their action results from the complementarity of the different products that compose them and give them, to a certain extent, their healing properties. They protect wounds from the surrounding environment with an antiseptic coating. They stimulate the development of vascularization and regulate epidermization.
- These topical forms consist mainly of a lipid mixture (lanolin, petrolatum, glycerin ...) in which are added acids (salicylic, benzoic, malic), minerals (zinc oxide, titanium) or halides (iodide of starch).
- Some also contain collagen, fibrinogen, enzymatic serum proteolysate (amino acid supply) or vitamins (vitamin A) hormones (4-chlorotosterone acetate).
- metformin as a topical composition needs to be frequently repeated to provide an effect on healing.
- the rat showed that radiolabeled metformin deposited on a wound in a gel remained very short at the local level.
- metformin turns out to be an extremely hydrophilic compound, which makes it easily soluble in exudates and causes its very fast passage to the wound.
- the contact time between metformin and the wound receptors requiring to be activated locally is therefore very short and leads to a weak pharmacological response.
- topical compositions of the type proposed in patent F 2 809 310 do not make it possible to treat the wound for more than a few hours. It is necessary to renew its application regularly. However, for many wounds, it is necessary to apply a local treatment promoting healing for several days or weeks, to obtain good healing, and avoid the renewal of treatment to limit the risk of infection related to the manipulation of the compositions.
- a device such as a dressing, including metformin
- the dressing should ideally be applied for a duration of about 72 hours.
- a too frequent change of the dressing induces additional costs with regard to the expenses of nursing personnel necessary to change said dressing.
- a change that is too frequent can also increase the risk of infections. Indeed, at the time of removal of the dressing, the wound is exposed to bacteria present in the environment.
- metformin for exudates, it tends to be released too quickly on the wound, so that a peak concentration of metformin is released by the dressing in the hours following its application , and the beneficial effects of the treatment do not last more than a few hours.
- the dressing should instead allow a controlled and continuous release of metformin for several days, including for about three days.
- a sufficient amount of metformin should be released upon application of the device, and then a lower but continuous release of metformin should be maintained for the duration of the procedure.
- application of the device to the wound to maintain the desired effects.
- it is a question of administering a particular release profile involving a bolus in the first stages of application of the formulation, and then maintaining a lower level of metformin release throughout the duration of the formulation. treatment.
- the present invention aims to respond to these problems, by proposing a device dressing type comprising metformin, allowing a release of it in a continuous profile and controlled for several days.
- the invention thus has, according to a first aspect, a dressing comprising an interface layer comprising an elastomeric matrix, said matrix comprising metformin, its salts and its complexes, characterized in that the metformin has a particle size defined by a ⁇ 50 ⁇ 300 ⁇ and a ⁇ 90 ⁇ 600 ⁇ .
- the dressing according to the invention may be in the form of a frame coated with such an elastomeric matrix, or a self-supporting interface dressing comprising said unsupported elastomeric matrix.
- the invention also relates to a dressing comprising metformin, characterized in that the percentage of metformin release after 72 hours is between 40 and 100% of the amount of metformin introduced into the dressing.
- the invention also relates to a method of manufacturing a dressing as described above, characterized in that it comprises:
- preparing an interface layer formed of an elastomeric matrix by: i. preparation of an elastomeric matrix by dispersion of metformin having a particle size defined by a ⁇ 50 ⁇ 300 ⁇ and a ⁇ 90 ⁇ 600 ⁇ , its salts and complexes in an elastomer,
- a frame with the elastomeric matrix prepared in step i or the hot casting of said matrix, preferably on an etched plate forming, for example, the imprint of a mesh or square grid mesh
- the subject of the invention is a dressing, for its use for the healing of a wound or the use of such a dressing for the healing of a wound.
- the dressing according to the present invention comprises an interface layer comprising an elastomeric matrix, said elastomeric matrix comprising metformin having a particle size defined by a ⁇ 50 ⁇ 300 ⁇ and a ⁇ 90 ⁇ 600 ⁇ , its salts and its complexes.
- the interface layer of the dressing is in particular intended to be placed in contact with the wound.
- the elastomeric matrix comprises in particular at least one elastomer.
- the elastomer may be chosen from triblock block polymers of the ABA type comprising two styrene terminal blocks and a central block B which is a saturated olefin such as, for example, ethylene-butylene or ethylene-propylene.
- These triblock copolymers may be optionally combined with AB type diblock copolymers comprising a styrene block A and an ethylene-propylene or ethylene-butylene B block.
- KRATON POLYMERS under the name KRATON G®, and in particular under the name KRATON G 1651®, KRATON G 1654® or KRATON G 1652® for block copolymers poly (styrene - (- ethylene-butylene -) - styrene ) (abbreviated SEBS); by the company KURARAY under the name SEPTON® for block copolymers poly (styrene - (- ethylene-propylene -) - styrene) (abbreviated to SEPS).
- triblock and diblock copolymers As an example of commercial mixtures of triblock and diblock copolymers, mention may be made of the product marketed by the company KRATON POLYMERS under the name KRATON G1657®, the olefin block of which is ethylene-butylene. As an example of a particular mixture of triblock and diblock copolymers that can be produced in the context of the present invention, mention may be made of the mixture: a triblock SEBS, such as in particular the product marketed by KRATON POLYMERS under the name KRATON G 1651®; and
- poly (styrene-olefin) diblock copolymer such as in particular poly (styrene-ethylene-propylene) marketed by KRATON POLYMERS under the name KRATON G 1702®.
- SEBS or SEPS triblock copolymers having a styrene content of between 25 and 45% by weight relative to the weight of said SEBS or SEPS and having a medium or high molecular weight and a Brookfield viscosity at less than 300 cPs (measured at 25 ° C for a 10% solution in toluene).
- KRATON G1650® has a molecular weight of 213,000-240,000 Da
- KRATON G 1654 has a molecular weight of 180,000 Da. This difference in molecular weight is likely to impact the Brookfield viscosity at 25 ° C for a 10% elastomer solution.
- the Brookfield viscosity at 25 ° C for a 10% solution of KRATON G1651® is 1800 cPs against 410 cPs for KRATON G1654®.
- the 5 kg stress-free hot fluidity is also impacted by this variation in molecular weight: it is 5 g / 10 min for the KRATON G1651® against 22 g / 10 min for the KRATON G1654®.
- the elastomer may be chosen from block copolymers of poly (styrene - (ethylene-butylene) styrene) of high molecular weight, that is to say having a molecular weight greater than 200,000 Da.
- the elastomers for which the best release profile of metformin has been obtained are the triblock block copolymers sold under the name Krone G 1651®. This is particularly true when the elastomeric matrix is coated on a frame.
- the elastomeric matrix advantageously comprises an elastomer content ranging from 2 to 15% by weight, preferably from 3 to 12% by weight, relative to the total weight of the elastomeric matrix. metformin
- the elastomeric matrix used in the interface layer of the dressing according to the present invention comprises metformin having a particle size defined by a ⁇ 50 ⁇ 300 ⁇ and a ⁇ 90 ⁇ 600 ⁇ , its salts and its complexes.
- Metformin is an oral antidiabetic of the biguanide normoglycemic family used in the treatment of type 2 diabetes. Its role is to reduce the insulin resistance of the carbohydrate intolerant organism and to reduce hepatic gluconeogenesis. The mode of administration of metformin is per os. Metformin is absorbed in the small intestine, circulates in the blood unconnected and is excreted unchanged by the kidneys. Its mechanism of action is complex and is not yet fully understood. Metformin is a normoglycemic agent: it does not act on the insulin secretion, nor on the insulin sensitivity of tissues that use glucose (muscles, adipose tissue).
- Metformin also has a role in the inhibition of gluconeogenesis, by inhibiting mitochondrial glycerophosphate dehydrogenase, and in membrane transport of glucose (decreased intestinal resorption). It also increases the release of Glucagon-like peptide-1, inhibits the glucagon pathway, increases lactate production by enterocytes.
- the metformin used is in the form of a metformin hydrochloride.
- the particle size of metformin when calculated according to the Fraunhoffer optical model between 0.375 ⁇ and 2000 ⁇ , measured by laser with the dry powder module, corresponds to the following characteristics:
- the particle size distribution of metformin is unimodal.
- 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.
- the amount of metformin used is adapted according to the desired release kinetics.
- the interface layer comprises from 0.01 to 4.0 mg / cm 2 , preferably from 0.1 to 2.5 mg / cm 2 , advantageously from 0.1 to 1.8 mg / cm 2 of metformin.
- This value is related to the active surface of the interface layer, that is to say the surface intended to release the active ingredient as opposed to nonactive portions of the dressing, also called “sidewalk", generally allowing the attachment of this one. around the area to be treated.
- the metformin is incorporated in an amount such that the percentage of metformin released after 72 hours is between 40 and 100% of the amount of metformin introduced into the dressing.
- metformin is incorporated in such an amount that the percentage of metformin released after 24 hours is between 25 and 60% of the amount of metformin introduced into the dressing.
- the metformin is incorporated in an amount such that the percentage of metformin released after 4 hours is between 10 and 40% of the amount of metformin introduced into the dressing.
- the elastomeric matrix according to the invention may also comprise a salting agent.
- the salting agent is chosen from the copolymer of 2-methyl-2 [(1-oxo-2-propenyl) amino] - 1-propanesulfonic acid and 2-hydroxyethyl ester of propenoic acid or mixture of 2-octyl-1-dodecanol, D-xylopyranoside, 2-octyldodecyl and polyethylene glycol dipolyhydroxystearate.
- copolymer of the salt of 2-methyl-2 [(1-oxo-2-propenyl) amino] -1-propanesulfonic acid and the 2-hydroxyethyl ester of propenoic acid is for example marketed under the name SEPINOV. EMT10® by the company SEPPIC.
- the mixture of 2-octyl-1-dodecanol, D-xylopyranoside, 2-octyldodecyl and polyethylene glycol dipolyhydroxystearate is for example marketed under the trade name EASYNOV® by the company SEPPIC.
- the release agent is present in an amount ranging from 0.01 to 10% by weight, preferably 0.05 to 5% by weight, relative to the total weight of the elastomeric matrix.
- the copolymer of the salt of 2-methyl-2 [(1-oxo-2-propenyl) amino] -1-propanesulfonic acid and the 2-hydroxyethyl ester of propenoic acid is used as a salting agent, it is preferably used in an amount ranging from 0.01 to 1.9%, preferably 0.05 to 1.5%, more preferably from 0.1 to 1% by weight. , relative to the total weight of the elastomeric matrix.
- the elastomeric matrix may also comprise at least one hydrocolloid.
- hydrocolloid or hydrocolloid particles is meant here any compound usually used by those skilled in the art for its ability to absorb aqueous liquids such as water, saline or wound exudates.
- hydrocolloids any suitable hydrocolloidal compound, such as, for example, pectin, alginates, natural vegetable gums (Karaya gum), cellulose derivatives such as carboxymethylcelluloses (CMC) and their alkali metal salts (salts of sodium or calcium of carboxymethylcellulose known under the reference of CMC Blanose 7H4XF®), as well as synthetic polymers based on superabsorbent acrylic acid salts, such as, inter alia, the products sold by BASF® under the name Luquasorb 1003 ®, or by CIBA Specialty Chemicals® under the name Salcare SC91®, as well as mixtures of these compounds.
- CMC carboxymethylcelluloses
- SBA Specialty Chemicals® under the name Salcare SC91®
- hydrocolloids preferred in the context of the present invention are the alkali metal salts of carboxymethylcellulose, and in particular sodium carboxymethylcellulose.
- the size of the hydrocolloid particles is advantageously between 50 and 100 microns, in particular of the order of 80 microns.
- the amount of hydrocolloids incorporated in the elastomeric matrix may advantageously be from 1 to 25% by weight, preferably from 10 to 20% by weight, and more preferably from 12 to 16% by weight, relative to the total weight of the elastomeric matrix.
- the plasticizer may advantageously be from 1 to 25% by weight, preferably from 10 to 20% by weight, and more preferably from 12 to 16% by weight, relative to the total weight of the elastomeric matrix.
- the elastomer may be plasticized by addition of an oily element which makes it possible to obtain a highly cohesive, elastic gel with a greasy appearance.
- the oil element will preferably be chosen from a mineral oil having both good compatibility with the previously described elastomers and a recognized tolerance towards skin tissues.
- Paraffin oils preferably of low viscosity, or mixtures of paraffin oil and petrolatum, will preferably be used.
- plasticizing oils that are particularly suitable, mention may be made of the products sold by SHELL under the names ONDINA® and ISELLA® which consist of mixtures based on naphthenic and paraffinic compounds or by the company Hansen & Rosenthal under the names Pionier® or by ExxonMobil under the names Marcol® or by Petro Canada under the names Puretol®, or by Sonneborn under the name Blandol®.
- White mineral oils such as the oil marketed by Hansen & Rosenthal under the name Pionier 2076 P® will preferably be used.
- the plasticizer is a mixture of mineral oil, preferably paraffin oil with petroleum jelly, preferably from 50 to 98% by weight of paraffin oil and from 2 to 15% by weight. Vaseline weight.
- the elastomeric matrix may also comprise at least one tackifying resin to give them an adhesive character facilitating their positioning on the wound.
- the tackifying resins that can optionally be used in the composition of the elastomeric matrices according to the invention are chosen in particular from low molecular weight polyisobutylenes. In general, the use of hydrogenated resins is preferred. such as Escorez® resins of the 5000 series, and even more preferentially, the Escorez 5380® resin.
- the elastomeric matrix may further comprise one or more antioxidant agents.
- antioxidant any molecule that decreases or prevents the oxidation of other chemicals.
- the antioxidant may be chosen from phenolic antioxidants, such as, for example, the products sold by CIBA-GEIGY® under the name Irganox 1010®, Irganox 565® and Irganox 1076®, as well as the sulfur-containing antioxidants, such as, for example, dibutyldithiocarbamate. zinc marketed by AKZO® under the name PERKACIT ZDBC®.
- the antioxidant used will be Irganox 1010®.
- antioxidants may be used in an amount of about 0.05 to 1% by weight, preferably from 0.1 to 0.5% by weight, based on the total weight of the elastomeric matrix.
- the elastomeric matrix may comprise one (or more) other active substance (s) allowing to induce or accelerate the cicatrization or that may have a favorable role in the treatment of a wound.
- agents that promote healing such as retinol, vitamin A, vitamin E, N-acetylhydroxyproline, extracts of Centella Asiatica, papain, silicone, essential oils of thyme, niaouli, rosemary, sage, l hyaluronic acid, potassium sucrose octasulfate, sucralfate, allantoin
- antibacterial agents such as salts or silver complexes (such as silver sulphates, silver nitrates, silver sulphonamides or silver-based zeolites), zinc or copper salts , metronidazole, neomycin, penicillins, acid clavulanic, tetracyclines, mynocycline, chlorotetracycline, aminoglycosides, amikacin, gentamicin, probiotics;
- antiseptics such as chlorhexidine, trichlosan, biguanide, hexamidine, thymol, lugol, povidone iodine, benzalkonium chloride and benzethonium;
- anti-pain agents such as paracetamol, codeine, dextropropoxyphene, tramadol, morphine and its derivatives, corticosteroids and their derivatives;
- lidocaine such as lidocaine, benzocaine, dibucaine, pramoxine hydrochloride, bupivacaine, mepivacaine, prilocaine, etidocaine;
- anti-inflammatories 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;
- NSAIDs nonsteroidal anti-inflammatory drugs
- polymer matrix implemented according to the invention may also comprise one or more other compounds known for their action in the debridement phase, for example:
- the elastomeric matrix implemented in the present application comprises in particular the following elements:
- metformin its salts or complexes
- At least one salting agent selected from the copolymer of 2-methyl-2 [(1-oxo-2-propenyl) amino] -1-propanesulfonic acid salt and the 2-hydroxyethyl ester of the acid; propenoic acid or a mixture of 2-octyl-1-dodecanol, D-xylopyranoside, 2-octyldodecyl and polyethylene glycol dipolyhydroxystearate,
- the elastomeric matrix consists essentially of:
- - 0.5 to 15% preferably 1 to 10% by weight, relative to the total weight of the matrix, metformin, its salts or its complexes; - 2 to 15%), preferably 3 to 12% by weight, relative to the total weight of the matrix, of at least one elastomeric polymer;
- a release agent chosen from the copolymer of the salt of 2-methyl-2-acid [(1-Oxo-2-propenyl) amino] -1-propanesulfonic acid and 2-hydroxyethyl ester of propenoic acid or the mixture of 2-octyl-1-dodecanol, D-xylopyranoside, 2-octyldodecyl and polyethylene glycol dipolyhydroxystearate.
- the elastomeric matrix consists essentially of: 0.5 to 15%, preferably 1 to 10% by weight, relative to the total weight of the matrix, of metformin, its salts or its complex;
- a release agent chosen from the copolymer of the salt of 2-methyl-2-acid [(1-Oxo-2-propenyl) amino] -1-propanesulfonic acid and 2-hydroxyethyl ester propenoic acid or the mixture of 2-octyl-1-dodecanol, D-xylopyranoside, 2-octyldodecyl and polyethylene glycol dipolyhydroxystearate.
- the elastomeric matrix may be coated on a frame to form the interface layer, or molded by hot casting, for example on a plate, then demolded to obtain a self-supporting interface dressing.
- weft is meant a structure which, in the context of the present invention, may consist of any perforated material such as a perforated film, a thermoplastic net, a woven fabric, a knit, or a nonwoven, preferably elastic for better hold of the dressing on the skin.
- the materials constituting the weft are preferably polymeric such as polyamide, polyurethane, polyester, polyether, polyvinyl chloride, polyvinylidene chloride, polyvinyl alcohol, polyvinyl acetate, polystyrene, polyvinyl fluoride, a polyolefin such as polyethylene or a polyethylene.
- polypropylene a material based on a polyether polyester copolymer, a polyester or polyether polyurethane copolymer, a polyether polyamide copolymer.
- the weft may be formed of a yarn fabric of flexible material.
- This weft is in the form of an open wide mesh fabric and can be obtained by weaving or knitting processes to form open meshes of regular size, square or polygonal. In the case of weaving, the stitches can be fixed by means of turn threads in order to obtain a good dimensional stability.
- the mesh size is such that the unit area of the openings is of the order of 0.5 to 10 mm 2 , preferably 0.5 to 3 mm 2 , the rate of opening of the fabric (ratio of the open area to the total area) being of the order of 50 to 90%.
- the yarn used to make the fabric is preferably a continuous filament yarn.
- continuous filament yarn is meant a yarn formed of one or more long, stranded filaments; the choice of long filaments makes it possible to avoid short fibers which may become detached from the support and disperse near the contact surface with the wound.
- the constituent material of the yarns is preferably of the hydrophobic type, of artificial or synthetic nature; these constituents, such as, for example, polyesters, polyamides, cellulose acetates make it possible to obtain long filaments and yarns with considerably fewer fibrils than the yarns obtained from short fibers, for example.
- the choice of certain synthetic materials such as polyesters also gives the possibility of heat setting the wide mesh structure of the support.
- the wide-meshed fabric is preferably made with yarns of the same kind, but it is also possible to use fabrics made for example with warp yarns and weft yarns which would be of a different nature.
- the nature of the yarn is, for example, a polyester of the polyethyl terephthalate type, a polyamide or a cellulose acetate; it is preferable to use a wide-knit fabric thermofixed with polyester (Tergal or polyethyl terephthalate) continuous yarns, for example fabrics marketed under the name of marquisette, which weights about 20 to 80 g / m 2.
- a frame such as that described in patent EP 2 793 773 will preferably be used.
- the elastomeric matrix may be coated on the previously described frame.
- the elastomeric matrix may also be molded by hot casting and then demolded once cooled in order to obtain a self-supporting interface dressing.
- the coating can be performed by any method known to those skilled in the art.
- the method of coating the weft with the polymeric matrix must make it possible to trap the threads of the weft well in the matrix, while leaving a majority of openings not closed by the polymeric matrix.
- the amount of polymeric matrix used will be about 50 to 300 g / m 2, and preferably 60 to 160 g / m 2. In the case of a self-supporting interface dressing, the amount of polymeric matrix used will be around 250 to 600 g / m.
- the coating is made hot, without solvent, according to a continuous process in which the weft belt is passed through a molten polymer matrix bath at 140-150 ° C .; the weft band covered with molten gel is then passed between two fixed rolls pressed against each other with a predetermined spacing so as to eliminate the excess of polymeric matrix. The amount of polymeric matrix remaining on the frame depends essentially on the gap imposed between the fixed rolls. The covered frame is then cooled.
- the interface layer thus obtained is preferably non-adherent. Once cooled, it can then be covered with two protective films, for example thin films in polyester. Due to the non-adherent nature of the interface layer, these films do not require anti-adhesive treatment and their function is only to facilitate the extraction of the main packaging and the handling during placement on the wound.
- the interface layer is then cut into individual interface dressings in dimensions suitable for use, packaged in sealed pouches and sterilized.
- the interface layer according to the invention can be used in a similar way to the currently known interfaces such as, for example, Tulle Bold Light.
- the compress is placed in direct contact with the wound and can be used in single or multiple layers: the flexibility of the weft and the polymeric matrix makes it possible to apply the interface layer to the entire surface of the wound, overflowing all the way to the healthy skin.
- the dressing according to the invention comprises at least one interface layer as described above, intended to be placed in contact with the wound.
- dressing is intended to mean any medical device comprising an elastomeric matrix as described above, intended to be placed in contact with the wound.
- Such dressings are used in particular for the treatment of wounds.
- the choice of dressing depends on the type of lesion to be treated.
- absorbent dressings are favored in the case of the treatment of exudative wounds.
- the interface layer may for example be covered with an absorbent layer if the wound is highly exudative.
- Absorbent layer for the purpose of the present invention means any material or combination of materials used for the production of an absorbent layer in the field of dressings or hygiene products, such as diapers.
- hydrophilic absorbent foams for example based on polyurethane
- textile materials in particular woven fabrics and nonwovens based on absorbent fibers or gelling fibers
- superabsorbent materials for example based on acrylic polymers especially in the form of particles or fibers, preferably adhesive compositions containing hydrocolloid particles and hydrogels.
- the absorbent layer may also consist of nonwovens based on cellulose fibers. These nonwovens may also incorporate superabsorbent polymer particles commonly referred to as SAP such as acrylic polymers (sodium polyacrylates) in a proportion of between 10 and 60% by weight of the total weight of the compress in order to increase their capacity. absorption. Similarly, in order to promote the integrity of the nonwoven during absorption, the absorbent fibers may be associated with non-absorbent fibers such as heat-bonding fibers or bonded together using latex such as an EVA latex.
- nonwoven absorbents are well known to those skilled in the art and referred to as “hybrid bonded” or “multibonded” airlaid (see for example WO95 / 30394 or WO94 / 10954). Incidentally, it is possible to use as the absorbent layer a combination of the different non-woven fabrics mentioned above.
- nonwovens based on gelling fibers is also well known to those skilled in the art.
- gelling fibers of fibers based on hyaluronic acid, chitosan, collagen, pectin, alginates, sodium carboxymethylcellulose, sodium carboxymethylcellulose associated with alginates and fibers chemically modified cellulose, in particular carboxymethylated cellulose, or fibers based on superabsorbent polymers.
- these gelling fibers can be associated with other types of fibers to improve the properties of the nonwoven such as for example heat-binding fibers.
- Such nonwovens and the different fibers that can compose them are described for example in the following patent applications: WO 2007/025546, WO 2007/08531, WO 93/12275, WO 00/01425, WO 94/16746, WO 95 / 19795, EP 878 204, EP 1 435 247 or WO 86/01400.
- super-absorbent is meant here polymers in the form of powders, fibers or any other form that in contact with biological liquids gel.
- Hydrophilic polymers in the form of particles having superabsorbent properties are described, for example, in US Pat. No. 4,102,340.
- Absorbent materials such as crosslinked polyacrylamides are used for this.
- Preferred superabsorbent particles are composed of partially neutralized crosslinked polyacrylic acid. Examples that may be mentioned include the products marketed by BASF under the name LUQUASORB or those marketed by Ciba Specialty Chemicals under the name SALCARE.
- superabsorbents are generally used in combination with cellulose fibers as previously described or incorporated into preferably adhesive compositions used in hydrocolloid dressings.
- the absorbent layer may also consist of these superabsorbents, alone or incorporated between 2 distribution layers, or to a nonwoven of absorbent fibers such as for example cellulose or viscose fibers (see EP 358412 or US 6 096 942) .
- the interface layer and the optional absorbent layer may be held in place by a tape or an adhesive support for attachment to the peripheral areas of healthy skin away from the wound.
- the interface layer may be chosen so that the dressing has an adhesive strength on a steel plate of between 0.5 and 100 cN / cm, preferably between 5 and 40 cN / cm.
- This adhesive power is measured according to the method EN 1939 in which a dressing sample of 20 mm wide and 150 mm long is placed on a steel plate and in which the adhesive power is measured after 10 minutes. a dynamometer at a pulling speed of 100 mm / min at an angle of 90 °.
- the dressing thus produced can remain in place for a long time: in fact, the highly cohesive polymeric matrix does not disintegrate and the presence of a small amount of hydrocolloids maintains on the surface of the wound a degree of humidity sufficient to prevent that. to dry.
- the non-adherent nature of the polymeric matrix used it is possible, practically without risk, to remove the absorbent pad that does not adhere to the gel without moving the sterile interface layer to control the progress of the wound.
- the interface layer is translucent, allowing for transparent examination of the wound, it may be necessary to remove the interface layer as well to perform a more precise visual inspection or direct drug treatment of the current area.
- Dressings suitable for the present invention may be any commercially available dressing to which is associated the previously described interface layer intended to be placed in contact with a wound.
- Polyurethane films such as, for example, the products marketed by Smith & Nephew under the trademark Opsite®, or by the company 3M under the brand name
- Tegaderm® or by URGO Laboratories under the brand name Optiskin® consist of a thin film (of the order of 20 to 50 ⁇ ) transparent polyurethane adhesive. Their transparency allows a visual control of the area to be treated.
- These polyurethane films are semi-permeable, gas-permeable, and impervious to liquids and bacteria. They provide mechanical protection against friction, friction and shear phenomena;
- - Hydrocellular dressings such as for example the products marketed by Molnlycke under the trade mark Mepilex® or by Smith & Nephew under the Allevyn® brand, or by URGO Laboratories under the trademark Cellosorb®.
- These dressings generally consist of a support which may be a polyurethane film or a nonwoven, an absorbent layer which may be a polyurethane foam. The face intended to come into contact with the wound of this absorbent layer may be covered with an adhesive coating mass or not.
- These dressings have a high absorption capacity, by capillarity and / or retention within the hydrocellular structure; - Hydrofiber dressings, such as for example the products marketed by
- - Alginates such as for example the products marketed by Smith & Nephew under the Algisite® brand or by Coloplast under the Seasorb® soft brand or by Urgo Laboratories under the Urgosorb® brand.
- These dressings are generally in the form of compresses or wicks. They consist of natural polysaccharides and gell in contact with exudates. They have a very high absorption capacity and can also "trap" bacteria, thereby controlling bacterial contamination.
- the present invention also relates to a method of manufacturing a dressing as described above, characterized in that it comprises:
- preparing an interface layer formed of an elastomeric matrix by: i. preparation of an elastomeric matrix by dispersion of metformin having a particle size defined by a ⁇ 50 ⁇ 300 ⁇ and a ⁇ 90 ⁇ 600 ⁇ , its salts and complexes in an elastomer,
- a frame with the elastomeric matrix prepared in step i or the hot casting of said matrix, preferably on an etched plate forming, for example, the imprint of a mesh or square mesh grid.
- the invention also relates to the use of the dressing as described above, for the healing of wounds, and a dressing as described above for its use for healing wounds.
- FIG. 1 is a graphical representation of the ideal non-cumulative dissolution profile evaluated in mg / cm 2 of salted active ingredient.
- FIG. 2 is a graphical representation of the cumulative dissolution profiles evaluated in mg / cm 2 of active ingredient released from the dressings described in Example 1 to Example 7.
- FIG. 3 is a graphical representation of the non-cumulative dissolution profiles evaluated in mg / cm 2 of active ingredient released from the dressings described in Example 1 and in Example 7.
- FIG. 4 is a graphical representation of the cumulative dissolution profiles evaluated in ⁇ g / cm 2 of active ingredient released from the dressings described in Example 8 to Example 12.
- FIG. 5 is a graphical representation of the non-cumulative dissolution profiles evaluated in ⁇ g / cm 2 of active ingredient released from the dressings described in Example 8 to Example 12.
- FIG. 6 is a graphical representation of the cumulative dissolution profiles, evaluated in ⁇ g / cm 2 of active ingredient released from the dressings described in Example 13 to Example 16.
- FIG. 7 is a graphical representation of the non-cumulative dissolution profiles evaluated in ⁇ g / cm 2 of active ingredient released from the dressings described in Example 13 to Example 16.
- FIG. 8 is a graphical representation of the cumulative dissolution profiles, evaluated in ⁇ g / cm 2 of active ingredient salted out from the dressings described in Example 17 to Example 20.
- FIG. 9 is a graphical representation of the non-cumulative dissolution profiles evaluated in ⁇ g / cm 2 of active ingredient released from the dressings described in Example 17 to Example 20.
- FIG. 10 is a graphical representation of the cumulative dissolution profiles, evaluated in ⁇ g / cm 2 of active ingredient released from the dressings described in Examples 21 and 22.
- FIG. 11 is a graphical representation of the non-cumulative dissolution profiles evaluated in ⁇ g / cm 2 of active ingredient released from the dressings described in Examples 21 and 22.
- the following examples illustrate, in a nonlimiting manner, the invention which is the subject of the present application.
- the carboxymethylcellulose and metformin are premixed and sieved at 315 ⁇ .
- Petrolatum and half of the oil are introduced into a kneader at a set temperature of 115 ° C., at a speed of 75 to 120 rotations per minute (rpm), and then the sieved carboxymethylcellulose and metformin powders are introduced. It is kneaded for 15 minutes.
- the set temperature is increased to 150 ° C. Then half of the oil, the elastomer and the antioxidant are introduced. It is kneaded for 40 minutes (until a smooth and homogeneous mixture is obtained). The salting agent is introduced 15 minutes before the end.
- Interface dressings consisting of a weft (or marquisette) (weft 601 marketed by MDB TEXINOV) coated with elastomeric matrix were developed using the elastomeric matrices of Examples 1 to 21.
- HPLC system equipped with a UV detector, a sample changer and a column oven
- Acetonitrile low UV for analysis For example: ref. VWR 20048.290 or equivalent, Sodium chloride for analysis.
- ref. VWR 27810.295 or equivalent purified water HPLC quality.
- the mobile phase is a solution of ammonium dihydrogenphosphate at 17 g / L to which 2% of acetonitrile is added.
- the physiological saline used during the analysis will be pre-thermostated at 32 ° C.
- the analyzed test solutions are quantified with respect to the calibration line.
- the results obtained from the calculator are given in ⁇ g / mL and are reported in Table 2.
- the identification of the various tests is also indicated as follows:
- G grammage of the frame (g / cm 2 ). In the case of these dressings, the grammage G of the weft is 28 g / m 2 .
- the cumulative release results at each sampling point are expressed in ⁇ g / cm 2 and in percentage (%).
- A%, B%, C%, D% and E% which respectively denote the cumulative release at 4h, 7h, 24h, 48h and 72h in% (within 10 "1 ).
- Vaseline (Vaseline Codex A
- FIG. 2 is a graphical representation of the cumulative release of examples 1 to 7.
- FIG. 3 is a graphical representation of the non-cumulative release of examples 1
- the release agents with the best kinetics and the best released quantity are SEPINOV EMT10® and Easynov®. They indeed allow the best compromise between release profile with a bolus and a slow and continuous release of metformin, and a total amount of metformin salted out high.
- Table 15 average release of metformin cumulated in ⁇ g / cm 2 Average cumulated release ⁇ g / cm 2 )
- Table 16 mean of release of metformin not cumulated in ⁇ g / cm 2
- FIG. 4 is a graphical representation of the cumulative release of Examples 8 to 12.
- FIG. 5 is a graphic representation of the non-cumulative release of Examples 8 to 12.
- the level of release agent in this case Sepinov EMT 10, has an influence on the amount of metformin released in 72 hours. Indeed, the higher the level of Sepinov EMT 10, the higher the amount of metformin released is high This correlation is however not proportional.
- the non cumulated results show that the quantity released at each sampling (4h, 7h, 24h, 48h, 72h) is dependent on the rate of Sepinov EMT 10 contained in the matrix.
- the formulation containing no salting agent (Example 8) has a gradual release profile but the amount of metformin released is less important than in the presence of a salting agent, which released amount may be insufficient in some applications where a larger amount of metformin should be released throughout the use of the dressing.
- Vaseline (Vaseline Codex A from Synteal) 5 5 5
- Figure 6 is a graphical representation of the cumulative release of Examples 13 to 16.
- FIG. 7 is a graphical representation of the non-cumulative release of Examples 13 to 16.
- the models of Examples 13 to 16 tested have a similar release profile. However, the release values obtained make it possible to distinguish the models of Examples 13 and 14 of the models of Examples 15 and 16. In fact, at 72h, the models of Examples 13 and 14 release about 86% of metformin. The presence or absence of petrolatum has no impact on the release. The models of examples 15 and 16, meanwhile, release about 75% of metformin at 72h without highlighting an impact of the oil change (Puretol vs Pionier) on the released quantities of metformin.
- the oil change Puretol vs Pionier
- Pentacrythitol Tetrakis3- (3,5-di-tert-butyl-4-hydroxyphenyl) propionate (Irganox 0.12 0.12 0.12 0.112 1010 BASF)
- Metformme of IPCA 5 The metformins tested in Examples 17 to 20 are distinguished by their particle size as explained in the following table:
- Figure 8 is a graphical representation of the cumulative release of Examples 17 to 20.
- Figure 9 is a graphical representation of the non-cumulative release of Examples 17 to 20.
- CMC Blanose Sodium carboxymethylcellulose
- Vaseline-Paraffin Blend Liquid Paraffin and Wax
- Example 18 shows a progression. less metformin release than the other examples.
- the non-cumulative release curve shows that after 10 h, the curve of Example 18 is the one that releases the least metformin.
- Example 22 demonstrated an unexpected release: indeed, when the elastomeric matrix is used in a self-supported interface dressing, the release of metformin is improved relative to the same matrix coated on a frame.
- metformin samples having a small particle size distribution are those for which the dissolution was the least rapid. Now, usually, the smaller the particle size, the faster the dissolution.
- the particle size is ⁇ 50 ⁇ 200 ⁇ , ⁇ 90 ⁇ 510 ⁇ .
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Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR1656677A FR3053892A1 (en) | 2016-07-12 | 2016-07-12 | DRESSING FOR THE CONTROLLED AND PROLONGED RELEASE OF METFORMIN |
PCT/FR2017/051910 WO2018011520A1 (en) | 2016-07-12 | 2017-07-12 | Dressing enabling the controlled and prolonged release of metformin |
Publications (1)
Publication Number | Publication Date |
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EP3484532A1 true EP3484532A1 (en) | 2019-05-22 |
Family
ID=57860931
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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EP17751436.1A Withdrawn EP3484532A1 (en) | 2016-07-12 | 2017-07-12 | Dressing enabling the controlled and prolonged release of metformin |
Country Status (5)
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US (1) | US11191866B2 (en) |
EP (1) | EP3484532A1 (en) |
CN (1) | CN109475656A (en) |
FR (1) | FR3053892A1 (en) |
WO (1) | WO2018011520A1 (en) |
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GB0808376D0 (en) | 2008-05-08 | 2008-06-18 | Bristol Myers Squibb Co | Wound dressing |
CN110179776B (en) * | 2019-05-31 | 2022-09-06 | 宁夏医科大学 | New application of metformin, metformin composition and preparation method and application of metformin composition |
CN115006376B (en) * | 2022-05-12 | 2023-11-24 | 南方科技大学 | Hydrogel spray and preparation method and application thereof |
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US4102340A (en) | 1974-12-09 | 1978-07-25 | Johnson & Johnson | Disposable article with particulate hydrophilic polymer in an absorbent bed |
US4650479A (en) | 1984-09-04 | 1987-03-17 | Minnesota Mining And Manufacturing Company | Sorbent sheet product |
US4901714A (en) | 1988-09-09 | 1990-02-20 | E. R. Squibb & Sons, Inc. | Bandage |
GB9126193D0 (en) | 1991-12-10 | 1992-02-12 | Courtaulds Plc | Cellulosic fibres |
SE508961C2 (en) | 1992-11-17 | 1998-11-23 | Sca Hygiene Prod Ab | Absorbent structure and absorbent articles containing the structure in question |
WO1994016746A1 (en) | 1993-01-22 | 1994-08-04 | Courtaulds Plc | Wound dressings |
GB9400994D0 (en) | 1994-01-20 | 1994-03-16 | Bristol Myers Squibb Co | Wound dressing |
SE510466C2 (en) | 1994-05-04 | 1999-05-25 | Sca Hygiene Prod Ab | A method of preparing an absorbent structure and an absorbent wound dressing containing an absorbent structure prepared according to the method |
NL1005812C1 (en) | 1997-04-15 | 1997-06-04 | Claus Jurgen Timmermans | Super absorbent wound dressing. |
US6096942A (en) | 1998-04-24 | 2000-08-01 | Pabban Development Inc. | Surgical dressing, and process for manufacturing same |
DK2036581T3 (en) | 1998-07-01 | 2012-09-24 | Convatec Ltd | Wound dressings and suitable materials for use therein |
FR2809310B1 (en) | 2000-05-26 | 2004-02-13 | Centre Nat Rech Scient | USE OF BIGUANIDE DERIVATIVES FOR MANUFACTURING A MEDICINAL PRODUCT HAVING A HEALING EFFECT |
DE60309425T2 (en) | 2003-01-06 | 2007-10-04 | Speciality Fibres And Materials Ltd. | Alginate tissue and superabsorbent wound dressing |
US7520406B2 (en) | 2005-07-08 | 2009-04-21 | S. C. Johnson & Son, Inc. | Device for dispensing a controlled dose of a flowable material |
US20090156974A1 (en) | 2005-08-31 | 2009-06-18 | Jens Hog Truelsen | Absorbent wound care device |
KR100858848B1 (en) * | 2006-05-23 | 2008-09-17 | 한올제약주식회사 | Pharmaceutical compositions and formulations of Metformin extended release tablets |
WO2008122993A1 (en) * | 2007-04-09 | 2008-10-16 | Panacea Biotec Limited | Controlled release formulation of coated microparticles |
EP2180905B1 (en) * | 2007-07-13 | 2016-09-07 | Coloplast A/S | A medical dressing comprising an antimicrobial agent |
CN102711738A (en) * | 2009-11-13 | 2012-10-03 | 百时美施贵宝公司 | Reduced mass metformin formulations |
FR2974004B1 (en) * | 2011-04-15 | 2014-05-02 | Urgo Lab | HYDROCELLULAR ABSORBENT DRESSING, ITS USES FOR THE TREATMENT OF CHRONIC AND ACUTE WOUNDS |
DK2524706T3 (en) * | 2011-05-19 | 2014-10-06 | Lohmann & Rauscher Gmbh & Co | Sterile wound dressing with a synthetic three-block elastomer |
DE102011120491A1 (en) * | 2011-09-02 | 2013-03-07 | BLüCHER GMBH | Wound dressing useful for treating wound e.g. mechanical wound, comprises multilayer structure comprising at least one hydraulic colloid layer, preferably collagen-containing layer and at least one activated carbon-containing layer |
WO2013093213A1 (en) | 2011-12-19 | 2013-06-27 | Laboratoires Urgo | Adherent interface dressing |
CN103446063B (en) * | 2013-08-26 | 2016-01-20 | 崔新刚 | A kind of compound formulation of compound metformin hydrochloride pioglitazone hydrochloride sustained-release pellet preparations and preparation technology |
KR101642193B1 (en) * | 2014-10-13 | 2016-07-25 | 씨제이헬스케어 주식회사 | An extended release pharmaceutical formulation of metformin and a preparation method thereof |
FR3030225B1 (en) * | 2014-12-19 | 2017-01-13 | Urgo Lab | DRESSING COMPRISING A SUPPORT AND A HYDROPHOBIC ELASTOMERIC MATRIX |
CN105125539A (en) * | 2015-08-05 | 2015-12-09 | 浙江华海药业股份有限公司 | Pioglitazone metformin tablet and preparation method thereof |
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2016
- 2016-07-12 FR FR1656677A patent/FR3053892A1/en not_active Withdrawn
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2017
- 2017-07-12 WO PCT/FR2017/051910 patent/WO2018011520A1/en unknown
- 2017-07-12 EP EP17751436.1A patent/EP3484532A1/en not_active Withdrawn
- 2017-07-12 CN CN201780043424.8A patent/CN109475656A/en active Pending
- 2017-07-12 US US16/317,120 patent/US11191866B2/en active Active
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FR3053892A1 (en) | 2018-01-19 |
CN109475656A (en) | 2019-03-15 |
WO2018011520A1 (en) | 2018-01-18 |
US20190184055A1 (en) | 2019-06-20 |
US11191866B2 (en) | 2021-12-07 |
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