WO2016135038A1 - Pansement pour plaies - Google Patents

Pansement pour plaies Download PDF

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Publication number
WO2016135038A1
WO2016135038A1 PCT/EP2016/053463 EP2016053463W WO2016135038A1 WO 2016135038 A1 WO2016135038 A1 WO 2016135038A1 EP 2016053463 W EP2016053463 W EP 2016053463W WO 2016135038 A1 WO2016135038 A1 WO 2016135038A1
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WO
WIPO (PCT)
Prior art keywords
adhesive
adhesive layer
wound dressing
group
layer
Prior art date
Application number
PCT/EP2016/053463
Other languages
English (en)
Inventor
Geofrey De Visscher
Mayu Takeiri
Original Assignee
Nitto Denko Corporation
Priority date (The priority date 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 date listed.)
Filing date
Publication date
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Publication of WO2016135038A1 publication Critical patent/WO2016135038A1/fr

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Classifications

    • 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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
    • A61K9/7061—Polyacrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7069—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained otherwise than by reactions only involving carbon to carbon unsaturated bonds, e.g. polysiloxane, polyesters, polyurethane, polyethylene oxide
    • 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
    • A61L15/58—Adhesives
    • 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
    • A61L2300/404—Biocides, antimicrobial agents, antiseptic agents
    • 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
    • A61L2300/412—Tissue-regenerating or healing or proliferative agents

Definitions

  • Wound dressings are known, in the art.
  • EP 272 149 Bl describes a hydrocolloid- based medical dressing containing active components such as antiseptic and anti-inflammatory agents
  • US 8821916 B2 describes a dry medical dressing in the form of foam that is capable of releasing anti-bacterial agents to a wound bed.
  • US 6312713 describes a thin-layered dressing for surface wounds which gradually releases drugs, such as analgesics. The drug is incorporated in a hydroph lic polymeric matrix and may be used topically.
  • WO 2007/098772 Al describes a dressing for the local treatment of pain in a wound, said dressing comprising an absorbent element and an active pain relieving composition.
  • US 2934066 A describes a wound covering coated with metals, especially silver, which is reported to have a disinfecting effect.
  • US 7270721 B2 describes an antimicrobial composite which comprises a first, liquid permeable layer and a second layer arranged on the first layer. An antimicrobial metal in elemental form is present between the first and second layers.
  • US 2010/01 6454 Al describes dressings comprising silicone elastomer cross-linked polymers that applied to closed wounds and cured at room temperature,
  • the present invention relates to a wound dressing comprising:
  • Ri and R 2 may be the same or different and are selected from the group consisting of hydrogen, -SO3M and a physiologically hydrolyzable chemical group, wherein M is a cation, preferably a metal cation, and the physiologically hydrolyzable chemical group is selected from the group consisting of alkyl, alkylcarboiiyl, alkenylcarbonyl arylcarbonyl, heteroarylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, alkylether, alkenylether, arylether, and lieteroarylether groups wherein the alkyl group or moiety consists of unsubstituted or substituted, straight-chain or branched-chain or cyclic alkyl groups having 1 -22 carbon atoms, wherein the alkenyl moiety consists of unsubstituted or substituted, straight-chain or branched-chain or cyclic alkenyl groups having 2-22 carbon atoms
  • the substrate can be an adhesive layer or a non-adhesive absorbent layer.
  • the compound according to formula (1) can be uniformly mixed in the substrate layer and/or it can be coated on the wound-facing side of the substrate layer.
  • the wound dressing of the invention is particularly suited as an adhesive patch for delivering compounds according to Formula (1) to treat wounds and inhibit or eradicate biofiims.
  • Figure 1 depicts a wound dressing having a backing layer, an adhesive substrate layer that comprises at least one compound according to Formula (1), and a release liner (the protective layer).
  • Figure 2 depicts a wound dressing having a backing layer, an adhesive layer, a non-adhesive substrate layer, and a release liner.
  • the non-adhesive substrate layer contains a compound according to Formula (1).
  • Figure 3 shows the release property of isosorbide from various wound dressings according to the invention.
  • Figure 4 shows the release amount of isosorbide from the wound dressing of example 1 .
  • Figure 5 shows the release rate of isosorbide from various wound dressings according to the invention after 4h and 24 h.
  • Figure 6 shows the peel force of various wound dressings according to the invention.
  • the terms “comprises”, “comprising”, “includes”, “including”, “has”, “having” or any other variation thereof are intended to cover a non-exclusive inclusion.
  • a wound dressing that comprises a list of components is not necessarily limited to only those components but may include other components that are not expressly listed or inherent to such a composition. That said, the terms “comprises”, “comprising”, “includes”, “including”, “ as”, “having” or any other variation thereof also cover the disclosed embodiment having no further additional components (i.e. consisting of those components).
  • a wound dressing comprising a backing layer and a substrate layer comprising a compound according to Formula (1) discloses the wound dressing with just these components as well as wound dressings comprising these components along with other unmentioned components (e.g. a release liner).
  • the present invention relates to wound dressings, in particular wound dressings that can be used in methods for treating wounds, methods of reducing scar formation, and methods of treating a biofilm hifection as well as for methods of inhibiting or eradicating tire formation of biofilms.
  • the present invention also relates to wound dressings for use in cosmetic methods of treating wounds and cosmetic methods of reducing scar formation.
  • Wounds that can be treated with a wound dressing according to the invention may be acute or chronic.
  • Acute wounds are wounds that proceed orderly through the three recognised stages of the healing process (i.e. the inflammatory stage, the proliferative stage and the remodelling phase) without a protracted time course.
  • Chronic wounds are those wounds that do not complete the ordered sequence of biochemical events because the wound has stalled in one of the healing stages.
  • a chronic wound is a wound that has not healed within at least. 30 days, preferably at least 40 days, more preferably at least 50 days, most preferably at least 60 days.
  • the wound to be treated may be a breach in, or demtdement of, the tissue for instance caused by surgical incision or trauma, e.g., mechanical, thermal, electrical, chemical or radiation trauma; a spontaneously forming lesion such as a skin ulcer (e.g. a venous, diabetic or pressure ulcer); a blister (e.g. a friction or thermal blister or a blister caused by pathogen infection such, as chicken pox); an anal fissure or a mouth, ulcer,
  • surgical incision or trauma e.g., mechanical, thermal, electrical, chemical or radiation trauma
  • a spontaneously forming lesion such as a skin ulcer (e.g. a venous, diabetic or pressure ulcer); a blister (e.g. a friction or thermal blister or a blister caused by pathogen infection such, as chicken pox); an anal fissure or a mouth, ulcer,
  • a “scar” in the sense of the present invention means normal scars, hypertrophic scars, keloid scars, contracture scars, atrophic scars and striae.
  • Symptoms of scars include skin discolorations (including redness, changes in pigmentation, or other discolorations e.g. from blanching), erythema, dry, flaky, or itchy skin, raised area above the surrounding skin, keloid formation, hypertrophy, scar pain, decreased vascularisation of the scar and/or surrounding tissue, reduced pliability, and poor aesthetic appearance (including quality and texture of the sear tissue).
  • the reduction of scarring can also be considered as the treatment (prevention or amelioration) of these symptoms.
  • biofilm is to be understood as having its ordinary meaning.
  • a biolilm is a sessile community of microorganisms characterized by cells that are attached to a substratum or interface or to each other, that are embedded in a matrix of extracellular polymers (more specifically extracellular polymers that they have produced), and that exhibit an altered phenotype with respect to growth rate and gene transcription (for example as compared to their "non-biofilm” or free-floating or planktonic counterparts).
  • the biofilms that may be treated in accordance with the invention are not limited, in terms of the microorganisms that they contain.
  • the biofilm may comprise any class, genus or species of microorganism, namely any microorganism that may form a biofilm.
  • Such microorganisms typically include bacteria, including any genus or species of bacteria.
  • the bacteria may be gram positive or gram negative, or gram test non-responsive.
  • the bacteria may be aerobic or anaerobic.
  • the bacteria may be pathogenic or non-pathogenic. It is particularly surprising that the molecules defined herein are able to kill bacteria in mature biofilms and the treatment of such biofilms is particularly preferred.
  • Biofilms comprising or consisting of Gram positive bacteria are preferred targets.
  • Biofilms comprising Staphylococcus are preferred targets, with biofilms comprising S. haemofyticus, S. aureus, and/or S. pidermidis being especially preferred.
  • Biofilms may also contain fungi, algae and other organisms such as parasitic protozoa in addition to the bacteria. Such mixed colony biofilms are also treatable according to the methods described herein.
  • a "biofilm-associated infection” is a microbial infection of an. object or a subject where it is known or suspected that the microbes are present as a biofilm.
  • a subject refers to a human, or any non-human animal subject.
  • a biofilm-associated infection will be an infection where the existence of a biofilm is relevant to a particular clinical condition, e.g. to the diagnosis or prognosis, to the treatment regimen, to the severity of the infection, to the duration of the infection up to the point of treatment or anticipated in the future.
  • Biofilms in chronic wounds are a preferred therapeutic target for the wound dressings of the present, invention. These chronic wounds include venous ulcers, diabetic ulcers, and pressure ulcers.
  • Venous ulcers for example, occur mostly in the legs, as a result of poor circulation (e.g., ischemia), malfunctioning valves of veins, or repeated physical trauma (e.g., repetitive injury).
  • Pressure ulcers may be present when local pressure that is exerted at or around a wound site is greater than blood pressure, for ins tance, such that poor circulation, paralysis, and/or bed sores may contribute to, or exacerbate, the chronic wound.
  • Diabetic ulcers may occur in individuals with diabetes mel tus. for example, persons in whom uncontrolled high blood sugar can contribute to a loss of feeling in the extremities, leading to repetitive injuries and/or neglect on the part of the individual to attend to injuries.
  • Biofilms in chronic wounds that have resulted from acute wounds such as gunshot or shrapnel wounds, bums, punctures, or surgical wounds (e.g. postoperative wound infections) can also be treated with wound dressings according to the invention.
  • Biofilms can be treated in other wounds such as those arising from radiation poisoning, malignancies, dermal infections, gangrene, nonhealing surgical wounds, pyoderma gangrenosum, traumatic wounds, acute arterial insufficiency, necrotizing fasciitis, and osteomyelitis (bone infection).
  • Treatment of a biofilni includes prophylactic treatment and encompasses a reduction in size of the biofilm, a reduction in number of living microorganisms within the biofilni and prevention or reduction in the tendency of microorganisms within the biofilm to break free and form new biofilm colonies.
  • the size, structure, integrity, and number of microbes in a biofilm can be analysed by any convenient method. For instance, scanning and transmission electronic microscopy is often used to assess the size, integrity and structure of a biofilm.
  • treatment includes an improvement, observed by clinician or patient, in one or more of the symptoms associated with the infection, 5.1 Backing layer
  • the backing layer of the wound dressing serves to support the substrate layer when the wound dressing is applied to a wound and may be of any suitable layer known for use as a backing layer in wound dressings e.g. a foam layer, a woven or non- woven layer, or an elastomer film,
  • a suitable layer known for use as a backing layer in wound dressings e.g. a foam layer, a woven or non- woven layer, or an elastomer film
  • the material that can be used as the backing layer include polyolefin such as polyethylene and polypropylene, polyester such as polyethylene terephthalate, polyamide such as nylon, polyvinyl chloride, and polyvinylidene chloride.
  • the backing layer may be a composite film containing such a single film laminated with paper, non oven cloth, woven cloth, knitted cloth or metal foil in addition to such a single film.
  • Elastomer films can provide strong support while maintaining flexibility and moisture penneability so as to exert an effect of fairly following the contour of the skin during sticking and lessening the irritation of the skin after placement.
  • the elastomer employable herein include polyethylene, polyvinyl chloride, ethylene- vinyl acetate copolymer, polyamide, polyester, polyurethane, and acrylic polymer. Particularly preferred among these elastomers are polyamide, polyester, polyurethane and acrylic polymer, which have a high permeability to water vapour and so do not impede the perspiration from the skin.
  • the thickness of the elastomer film is preferably predetermined to be from 10 pm to 150 pm, more preferably from 20 ⁇ . to 70 pm.
  • the modulus of the elastomer film, at 50% elongation is preferably predetermined to be from 0.2 to 15 N/imn2 as measured at ordinary temperature and humidity (23°C and 60% RH) so as to provide suitable flexibility and allows the backing layer to follow the contour of the skin.
  • the backing layer alone may have a moisture transmission rate of 500 to 14600 g/m 2 /24 hrs, preferably from 1000 to 2700 g/m 2 /24 hrs at 37°C if measured according to DIN EN 13726-2.
  • the backing layer may have a vapour transmission rate of 200 to 2000 L/m 2 /see 5 preferably from 400 to 1000 L/m 2 /sec at 2 mbar if measured according to EN ISO 9073 -Tl 5. Higher values than those mentioned above can be advantageous in order to delay the saturation point of the wound dressing in strongly secreting wounds. Lower values can be beneficial in assuring a moist micro- environment around the wound in the case of low-secretion wounds.
  • the backing layer can be transparent to allow the level of filling or moisture in the wound dressing or the status of the wound to be assessed without having to remove the dressing.
  • the backing layer can be filled with colouring agents.
  • one function of the substrate layer is to hold the compound according to Formula (1 ) until the wound dressing is applied to a wound. Upon application to a wound, the compound of Formula (1) migrates to the wound surface whereby it can exert its therapeutic effect.
  • the substrate layer can be an adhesive layer or a non-adhesive layer as explained in more detail below.
  • Ri and R 2 may be the same or different and are selected from the group consisting of hydrogen, -SO 3 M and a physiologically hydrolyzable chemical group,
  • M is a cation
  • the physiologically hydrolyzable chemical group is selected from the group consisting of alkyl, alkenyl, alkylcarbonyl, alkenylcarbonyl arylcarboiiyl, heteroarylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, heteroaryloxycarbonyl, alkylether, alkenylether, arylether, and lieteroarylether groups, wherein the alkyl group or moiety consists of unsubstituted or substituted, straight-chain or branched-chain or cyclic alkyl groups having 1 -22 carbon atoms, wherein the alkenyl moiety consists of unsubstituted or substituted, straight-chain or branched-chain or cyclic alkenyl groups having 2-22 carbon atoms, wherein the aryl moiety consists of unsubstituted or substituted phenyl, or phenalkyl groups wherein the alkyl moiety contains
  • Suitable substituents include: 3-12 member heterocycJe, C6-C 10 aryl, 5- 12 member heteroaryl, halogen (e.g. F, CI, Br), -NO : ; NH 2:S NR., -CN, -COR, - COOR, -CONR2, -OH, -OR, -OCOR, -SR, -SOR, -S0 2 R, -SONR 2 , -SO2 R2, wherein each R in the substituent is independently selected from H, C I -C I 0 alkyl, 3-10 member heterocycie, C6- C10 aryl, 5-12 member heteroaryl.
  • halogen e.g. F, CI, Br
  • M may be any suitable cation including, but not limited to, a hydrogen atom, a metal atom, or an ammonium or an alkylammonium ion.
  • M is preferably a metal cation such as a cation of an alkali metal or an alkaline earth metal.
  • Preferred metal cations are those selected from the metals Ag, Zn, AI, Li, Na, K, Mg and Ca, Metal cations based on Ag or Zn are useful because these metals can provide additional or complementaiy bactericidal or enzyme inhibiting properties.
  • M may be a monovalent or polyvalent cation. When M is a polyvalent cation, two compounds according to Formula ( 1 ) may share M as a cation (e.g. dication bridging).
  • Exemplary alkyl . groups for the alkyl, alkylcarbonyl, alkoxycarbonyl, and alkylether, of Formula ( 1 ) include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, hexyi, heptyl.
  • octyl nony , decyl, undecyl, dodecyl, tridecyl, as well as alkyl groups derived from fatty acids such valeric acid, isovaleric acid, caproic acid, enanthic acid, eapry!ic acid, peiargonie acid, capric acid, undecylic acid, lauric acid, tridecylie acid, myristic acid, pentadecylic acid, palmitic acid, margaric acid, stearic acid, nonadecylic acid, and arachidic acid.
  • fatty acids such valeric acid, isovaleric acid, caproic acid, enanthic acid, eapry!ic acid, peiargonie acid, capric acid, undecylic acid, lauric acid, tridecylie acid, myristic acid, pentadecylic acid, palmitic acid, margaric acid, stearic acid, nonadec
  • Exemplary alkenyl groups for the alkenyl, alkenylcarbonyl, and alkenylether of Formula ( 1) include ethylene, propylene, butylene, pentylene, exylene, and octylene, including those derived from fatty acids such as myristoleic acid, palmitoleic acid, sapienic acid, oleic acid, elaidic acid, vaecenic acid, linoleic acid, linoelaidic acid, a-linolenic acid, and arachidonic acid.
  • fatty acids such as myristoleic acid, palmitoleic acid, sapienic acid, oleic acid, elaidic acid, vaecenic acid, linoleic acid, linoelaidic acid, a-linolenic acid, and arachidonic acid.
  • Ri and R2 are selected from hydrogen, -SO3M, or a hydrocarbon group selected from alkyl, alkenyl, alkylcarbonyl, and alkenylcarbonyl, wherein the alkyl group or moiety consists of unsubstituted or substituted, straight-chain or branched-chain or cyclic alkyl groups having 1 -22 carbon atoms, and wherein the alkenyl moiety consists of unsubstituted or substituted, straight-chain or branched-chain or cyclic alkenyl groups having 2-22 carbon atoms. Ri and R2 may be the same or different.
  • Rj and R may both be hydrogen, or one of Ri and R2 may be hydrogen and the other selected from the groups defined above.
  • R] and i may both be methyl, or one of Ri and R2 may be methyl and the other selected from the groups defined above.
  • Ri and R2 may both be -COMe, or one of R
  • R i and Ri may both be -SO3M, or one of Rj and R 2 may be -SO3M and the other selected from the groups defined above.
  • Preferred compounds according to Formula (1 ) are those where R
  • C I -C I 8 alkyl group a branched C3-C18 alkyl group, a linear C2-C18 alkenyl group, or a branched C3-C18 alkenyl group.
  • R i and R 2 are the same and selected from the group consisting of H, -SO3M, -R3 or -CORj, wherein is a linear C I -C I 8 alkyl group, a branched. C3-C18 alkyl group, a linear C2-C 18 alkenyl group, or a branched C3-C18 alkenyl group.
  • compounds according to Formula (1) where at least one of Ri and. R; is - SO 3 M.
  • preferred compounds include those where one of Ri and R; is -SO3M, and the other is H, -R 3 or -COR3, wherein 3 is a linear CI -CI 8 alkyl group, a branched C3-C18 alkyl group, a linear C2-C18 alkenyl group, or a branched C3-C18 alkenyl group.
  • Ri and R2 are -SO3M, and the other is H, -R3 or -COR 3 , wherein R3 is a linear CI -CI O alkyl group, a branched C3-C10 alkyl group, a linear C2-C10 alkenyl group, or a branched C3-C10 alkenyl group.
  • R3 is a linear CI -CI O alkyl group, a branched C3-C10 alkyl group, a linear C2-C10 alkenyl group, or a branched C3-C10 alkenyl group.
  • and R are the same and are selected from either H, ⁇ C3 ⁇ 4, -C2H5, - COCH3, -COC2H5, or -SO3M.
  • Tlie compound according to Formula (1) may be any of the possible stereoisomers (e.g.
  • “Pharmaceutically acceptable salts”, as used herein, are salts that retain the desired biological activity of the parent compound and do not impart undesircd toxicological effects.
  • Phannaceuticaliy acceptable salt forms include various crystalline polymorphs as well as the amorphous form of the different salts.
  • the phannaceuticaliy acceptable salts can be formed with metal or organic counterions and include, but are not limited to, alkali metal salts such as sodium or potassium; alkaline earth metal salts such as magnesium or calcium; and ammonium or tetraalkyl ammonium, salts.
  • the salts can be organic or inorganic in nature.
  • Representative salts include acetate, benzenesulfonate, benzoate, bicarbonate, bisulfate, bitartrate, borate, bromide, calcium edetate, camsylate, carbonate, chloride, clavulanate, citrate, dihydrochloride, edetate, edisylate, estolate, esylate, fumarate, gluceptate, gluconate, glutamate, glycollylarsanilate, hexylresorcinate, hydrabamine, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isethionate, lactate, lactobionate, laurate, malate, maleate, mandelate, mesylate, methylbromide, methylmtrate, methylsulfate, monopotassium maleate, mucate, napsylate, nitrate, N- methyiglucamine, oxalate,
  • Solvates are addition complexes in which the compound is combined with an acceptable co-solvent in some fixed proportion.
  • Co-solvents include, but are not limited to, ethyl acetate, lauryl lactate, myristyi lactate, cetyl lactate, isopropyl myristate, methanol, ethanol, 1 - propanol, isopropanol, 1 -butanol, isobutanol, tert-butanol.
  • acetone methyl ethyl ketone, acetonitriJe, benzene, toluene, xylene(s), ethylene glycol, dichloromethane, 1 ,2-diehloroethane, N-methylformamidc, ⁇ , ⁇ -dimethylformamide, N-methylacetamide, pyridine, dioxane, and diethyl ether.
  • the term 'hydrate' is employed when the co-solvent is water.
  • the compound according to Formula (1 ) is present in an adhesive substrate or a non- adhesive substrate (see detailed discussion below), it is preferably that the sum amount of active compounds according to Formula (1 ) are formulated in the wound dressing in an amount suitable for release of 1 to 100,000 mg/m 2 or preferably 10 to 10,000 mg/m 2 , more preferably 30 to 3,000 mg/m " and most preferably 50 to 1000 mg/m 2 within the first 24 hours of administration. Typically the delivery is limited by a rest fraction remaining in the adhesive resulting in an effective .release of 10-80% of the active agent. Improved release times and release amounts of active compounds according to Formula (1) can be achieved by ensuring that the substrate is sufficiently thin, particualry when the substrate is an adhesive layer. 5.2.1. Adhesive substrate
  • the substrate layer that comprises a compound according to Formula (1) may be an adhesive layer, preferably a pressure-sensitive adhesive layer.
  • the compound according to Formula (1) may be distributed (e.g. uniformly) throughout the adhesive layer.
  • a composition comprising a solvent, an adhesive, and a compound according to Formula (i), together with any other components such as a tackifier, an organic liquid component and the like, may be layered (e.g. by coating) and then dried to form an adhesive layer in which the compound according to Formula (1) is distributed throughout.
  • the compound according to Formula (!) may be distributed on the wound-facing surface of the adhesive layer.
  • the wound facing side of the substrate layer is the side Dearest the wound when the dressing is applied to a wound.
  • the adhesive layer can first be prepared without the compound according to
  • Formula ( 1 ) this compound being coated on the surface of the adhesive layer in a subsequent processing step.
  • the compound according to Formula (1) is coated on the surface of the adhesive layer (e.g. by spray coating, dispense coating) it is preferable that the compound covers 50% or less of the surface area so as to maintain sufficient adhesion properties.
  • the compound according to Formula (1) may be coated in any regular or irregular pattern. In certain embodiments,
  • the pattern has translational symmetry along at least one axis, for example along two or three axes, hi certain embodiments, the pattern is in the form of a network of compound coating, such as a mesh pattern or a honeycomb pattern. In other embodiments the pattern consists of a plurality of islands, dots, or patches of compound separated by compound- free regions of the adhesive substrate.
  • the adhesive substrate layer may comprise a compound according to Formula (1) distributed throughout the adhesive layer as well as coated on the wound facing side as explained above.
  • the adhesive layer can be any adhesive known in the art of wound dressings (e.g. hydro colloid adhesive layer).
  • the adhesive layer is preferably a hydrophilic adhesive layer.
  • the adhesive layer contains as little water as possible.
  • the adhesive layer preferably comprises 0.5 wt.% or less of water (based, on the toai weight of the adhesive layer in the wound dressing), more preferably 0.1 wt.% or less of water, and even more preferably 0.01 wt.% or less of water.
  • the adhesive constituting the adhesive layer is not particularly limited, examples thereof include acrylic adhesives comprising acrylic polymer; styrene-diene- styrene block copolymers (e.g., styrene-isoprene-styrene block copolymer, styrene-butadiene- styreme block copolymer, etc.); rubber-based adhesives such as polyisoprene, polyisobutylene, polybutadiene and the like; silicone-based adhesives such as silicone rubber, dtmethylsiloxane- based, diphenylsiloxane-based and the like; vinyl ether-based adhesives such as polyvinyl methyl ether), polyvinyl ethyl ether), poly(vinyl isobutyl ether) and the like; vinyl ester-based adhesives such as vinyl acetate-ethylene copolymer and the like; polyester-based adhesives comprising carboxylate component such as di
  • Suitable commercially available adhesives that can be used for the present invention include those sold under the trade name acResin ® (BASF).
  • BASF acResin ®
  • Other suitable adhesives for the present invention are those described in EP 0528 191 Al , JP1 189926, EP 1323437 A l , FP 1 184039 Al, and EP 1285670 Al, all of which are incorporated herein by reference.
  • the adhesive layer may be a cross-linked adhesive layer obtained by subjecting the
  • the cross-linking treatment refers to a known treatment which can form bonds between molecules or in a molecule in an adhesive layer component constituting the adhesive layer.
  • the crosslinking treatment simultaneously enables maintenance of sufficient skin adhesive force of an adhesive patch and reduction of skin irritation such as pulling feeling of the skin and physical scraping of the stratum coraeum of the skin during peeling off of the adhesive patch from the skin surface.
  • Examples of the cross-linking treatment include a chemical crosslinking ' treatment using a crosslinking agent, a treatment for ion cross-linking, and a physical crosslinking treatment using electron beam, ultraviolet light and the like.
  • crosslinking agent examples include metal salts such as zinc acetate and the like, an epoxy compound, an amide compound, an amine compound, acid anhydride, peroxide, an isocyanate compound and the like.
  • a tackifier such as rosin- based resin, polyterpene resin, chroman-indene resin, petroleum-based resin, terpene-phenol resin, xylene resin and the like may be contained. These may be used alone or in a mixture of two or more kinds thereof.
  • Examples of the aforementioned petroleum-based resin include aliphatic (C5-based) petroleum resin, aromatic (C9-based) petroleum resin, copolymer series (C5-C9- based) petroleum resin and alicyclic saturated hydrocarbon resin obtained by partially or completely hydrogenating aromatic (C9-based) petroleum resin.
  • the alicyclic saturated hydrocarbon resin one having a. softening point by ring and ball method of 90 - 150°C is preferable.
  • the amount of the tackifier is not particularly limited, it is, for example, 10 wt% to 40 wt% based on the adhesive formulation from the aspects of imparting of appropriate adhesiveness and cost-effectiveness.
  • the adhesive layer can contain an organic liquid component
  • An organic liquid component is not particularly limited as long as it is liquid at room temperature (25°C). or is a mixture of two or more kinds which finally becomes liquid at room temperature (25°C).
  • organic liquid component examples include glycols such as ethylene glycol, propylene glycol, butylene glycol, di ethylene glycol, dipropylene glycol, triethylene glycol, tripropylene glycol, polyethylene glycol), poly(propylene glycol) and the like; vegetable fats and oils such as olive oil, castor oil and the like; animal fats and oils such as liquid lanolin; hydrocarbons such as squalane and liquid paraffin; various surfactants; ethoxylated stearyl alcohol; glycerol monoesters of fatty acids such as oleic acid monoglyceride, eaprylie acid monoglyceride and lauryl acid monoglyceride; dialkyl esters of polyalkylene glycol such as polyethylene glycol dilaurate, polyethylene glycol diisostearate, polypropylene glycol diisostearate, polypropylene glycol dioleate and the like; glycerol diesters such as glycerol di
  • the adhesive layer preferably has an average thickness of 5 ⁇ to 400 ⁇ , more preferably 10 ⁇ to 300 ⁇ , and even more preferably 20 ⁇ to 200 ⁇ .
  • the average thickness of the adhesive layer can be measured on the wound dressing before it is applied to a wound.
  • an adhesive layer lias an average thickness within the aforementioned range, the substrate has a superior skin protection effect, can sufficiently contain and deliver the compound according to Formula (1), and is superior in the skin adhesion performance.
  • the average thickness can be adjusted within these ranges to regulate the adhesiveness of the wound dressing to a patient. For instance, a thicker adhesive tends to lead to increased adhesiveness.
  • the peel force of the adhesive layer is preferably 1 N/25 mm or greater in view of providing a strong adhesion to the skin so as to effectively deliver a compound according to Formula (1). More preferably, the peel force is 1 .1 N/25 mm or greater, 1.2 N/25 mm or greater, and more preferably 1.3 N/25 mm or greater-
  • the upper limit of the peel force is not particularly limited, and relatively high upper limits can be used, particuallry if the adhesive layer is composed of a debondable (or switchable) adhesive.
  • Preferred upper limits of the peel force are 20 N/25 mm or less, more preferably 15 N/25 mm or less, more preferably 10 N/25 mm or less, more preferably 5 N/25 mm or less, and most preferably 3 N/25 mm. or less in view of reducing stress on the skin when the wound dressing is removed.
  • Any of the disclosed peel force lower limits can be combined with any of the disclosed peel force upper limits to define a suitable peel. force range for the purposes of this invention.
  • Exemplary peel force ranges include 1-20
  • N/25mm 1.1 -15 N 25mm, 1.2-10 N/25mm, 1.3-5 N/25mm, amd 1-3 N/25mm.
  • the peel forces recited above can be determined by Test Method A of the approved standard ASTM D3330M-04(2GT0) using the ear of a pig as the substrate.
  • the ear should be clean so as to be free of debris or other agents that might affect the peel force measurement.
  • the ear can be cleaned, in water to remove relatively large debris and then, after drying, pre-stripped with an acrylic-based adhesive (e.g. Transpose®, 3M, USA) to remove minor debris and any remaining agents that might affect the measurement.
  • an acrylic-based adhesive e.g. Transpose®, 3M, USA
  • Obtaining a constant peel force (within experimental error) between two sequential pre-stripping applications can be used as an indication that the ear is sufficiently clean to determine the peel force in accordance with the invention.
  • the adhesive layer whose peel force is to be measured should correspond to that (composition, thickness) which will be used in the wound dressing.
  • the substrate layer that comprises a compound according to Formula (1 ) may be a non-adhesive layer.
  • the substrate layer may be any of the layer types conventionally used for absorbing wound fluids, serum or blood in the wound healing art, including foams, sponges, gauzes, woven and nonwoven fabrics, and combinations thereof.
  • Suitable materials for the substrate layer include natural and synthetic polymeric absorbents (e.g. polyacrylate),
  • hydrocolloid/polysaccharide absorbents cellulosic absorbents, gum and resin absorbents, inorganic absorbents, gel-forming fluid-interactive adhesive dressings, wool, cotton, lint and superabsorbents (e.g. super absorbent particles (SAP) and/or super absorbent fibres (SAF)).
  • superabsorbents are water insoluble materials, typically in the form of fiber or flock material, which are capable of absorbing and retaining large amounts of water or other aqueous fluid in comparison to their own weight. Disposable goods manufactured using superabsorbents can be more comfortable, less bulky, and longer lasting than similar products made with traditional absorbents such as cellulose fibers.
  • liquid binds to the superabsorbent even under pressure (for example when a wound is in a position such that a patient may have occasion to sit on the dressing).
  • a cellulose matrix containing a superabsorbent e.g.,
  • carboxymethylcellulose can be used.
  • Sodium polyarcrylate is especially preferred, and particular in granular or powder form.
  • the compound according to Formula (1) may be distributed throughout the absorbent layer or may be coated on the wound-facing surface of the absorbent layer.
  • the compound according to Formula (1) may be coated on the absorbent surface in any regular or irregular pattern.
  • the pattern has translational symmetry along at least one axis, for example along two or three axes.
  • the pattern is in the form of a network of compound coating, such as a mesh pattern or a honeycomb pattern.
  • the pattern consists of a plurality of islands, dots, or patches of compound separated by compound- free regions of tire absorbent substrate.
  • the absorbent layer may comprise a stop layer on the skin-facing surface for preventing any speck or fluff from the absorbent layer to enter the wound.
  • the stop layer may be of any suitable material known in the art being capable of retaining absorbent material, such as a cellulose tissue, non-woven or a perforated polymeric film, knits, PP, PE, polyester or lycra.
  • the absorbent layer may further comprise a wound contacting layer at the wound-facing surface. This wound contacting layer may prevent adherence to the wound as well as in growth of the dressing.
  • the layer may preferably be highly permeable to wound exudate.
  • the wound contacting layer is in the fon of a polymer net.
  • the absorbent layer may be embossed or pre-cut in order to enhance flexibility of the dressing.
  • the basis weight of the absorbent layer may be in the range of 50-500g/m 2 , such as 100-400 g/m 2 .
  • the uncompressed thickness of the absorbent layer may be in the range of from 0.5 mm to 10 mm, such as 1 mm to 4 mm.
  • the free (uncompressed) liquid absorbency measured for physiological saline may be in the range of 5 to 30 g g at 25°C.
  • the wound dressing may comprise an adhesive in addition to the absorbent layer so that the wound dressing can be securely attached to a patient.
  • the adhesive may be on the substrate layer or on the backing layer on an area around the substrate layer.
  • the pattern of the adhesive may be any regular or irregular pattern. In certain embodiments the pattern has translalional symmetry along at least one axis, for example along two or three axes. In certain embodiments, the pattern is in the fonn of a network of adhesive coating, such as a mesh pattern or a honeycomb pattern. In other embodiments the pattern consists of a plurality of islands, dots, or patches of adhesive separated by adhesive- free regions of the substrate. In yet other embodiments, the pattern may be in the form of an adhesive-coated margin or annulus
  • any adhesive that is included in the wound dressing may also comprise a compound according to Formula (1).
  • a release liner may be laminated to the wound-facing adhesive surface to protect the adhesive layer prior to application of the dressing to a wound.
  • the release liner if present, is removed to expose the wound-facing side of the adhesive layer.
  • the release liner is optional and may not be necessary.
  • the wound dressing could be wound around on itself (e.g. in the form of a roll) such that the backing layer of the wound dressing provides suitable protection for the adhesive layer positioned immediately above it.
  • the release liner is not particularly limited, and examples of suitable materials are known in the field.
  • suitable materials include plastic films of polyester-based resin film such as poly(ethylene terephthalate); vinyl-based, resin film such as poly( vinyl chloride), po!y(vinylidene chloride), polystyrene and the like; acrylic resin film such as various acrylic and niethacry!ic polymers; polycarbonate resin film; polyimide resin film; cellulose-based resin film, such as acetyl cellulose, regenerated cellulose (cellophane), celluloid and the like; a laminate film of high-quality paper, glassine paper and the like and polyolefin-based film and the like.
  • a polyester-based resin film is preferably used.
  • the thickness of the aforementioned release liner is generally 10 ⁇ to 200 pm, preferably 25 ⁇ to 100 m.
  • the release liner is preferably treated for easy peeling on the interfacial surface side with an adhesive layer, so as to facilitate peeling from the adhesive layer. While the easy peeling treatment is not particularly limited, a known method can be applied. For example, a treatment method for forming a peeling-treated layer using a release agent containing a curable silicone resin as a main component by a coating method such as bar coating, gravure coating and the like can be mentioned.
  • the thickness of the aforementioned peeling-treated layer is preferably 0,01 ⁇ to 5 ⁇ to ensure releaseability and uniformity of the coating.
  • the thickness of the release liner having a peeling-treated layer is generally 10 ⁇ to 200 ⁇ , preferably 50 ⁇ to 100 ⁇ . from the aspect of handling property.
  • the release liner in the adhesive patch of the present invention may have an extended part outwardly extending over the adhesive patch main part. Since the extended part decreases the frequency of contact of the end of the adhesive patch main part against the inside of the package when the adhesive patch is contained in the package, even when an adhesive layer component oozes or protrudes from the end of the adhesive patch, main part, adhesion thereof to the inside of package which causes difficulty in taking the adhesive patch out from the package can be suppressed.
  • at least one part of the peripheral part of the adhesive patch main part preferably has a release liner with an extended part, and more preferably, the whole peripheral part of the adhesive patch main part has a release liner with an extended part.
  • the length of the aforementioned extended part of the release liner is preferably about 0.5 mm to 10 mm, more preferably about 1 mm to 3 mm, so as to achieve the aforementioned effects and ensure smooth insertion into a package.
  • the release liner may also have a back split part.
  • the aforementioned back split part is made by forming a broken line on the surface on the opposite side from the contact surface of the release liner with the adhesive layer.
  • the shape of the aforementioned broken line may be linear or curve (e.g., wave shape), or a combination of these.
  • the broken line may be a solid line or a dashed line, or a combination of these. Since a release liner has a back split part, the release liner can be easily removed when the adhesive patch is used.
  • the substrate may comprise further agents capable of providing a therapeutic effect.
  • the substrate may include one or more of an antimicrobial agents, antibiotic agents, anti-inflammatory agents,
  • antiproteolytic agents anesthetic agents
  • nutritional agents healing agents, coagulation agents, anticoagulation agents, oligodynamic metals, moisturizing agents, or angiogenesis stimulating agents.
  • Antimicrobial agent can. be a term for drugs, chemicals, or other substances that either kill or slow the growth of microbes.
  • antimicrobial agents are antibacterial drugs, including antibiotics, antiviral agents, antifungal agents, organometallic compounds such as silver carbenes, anti-parasitic drags, and oligodynamic metals to include silver and the like.
  • the antimicrobial agent can include an "Anti-microbial metal” which can be metals whose ions have an anti-microbial effect.
  • Metal or '"metals” includes one or more metals whether in the form of substantially pure metals, alloys or compounds including oxides, and salts such as nitrides, borides, sulphides, lialides, carboxylates, or hydrides. The metal may also be biocompatible.
  • Anti-microbial metals include Ag, An, Pt, Pd, Ir, Ga (i.e. the noble metals), Sn, Cu, Sb, Bi, Ce, and Zn.
  • Atoms, ions, molecules or clusters of the anti-microbial metal can have "Anti-microbial effect” when they are released.
  • the wound dressing can provide multiple means for providing bactericidal effects (e.g. the dianhydroliexitol sulphate; the Ag cation; and the optional additional antimicrobial agent).
  • the antimicrobial, agent can be one or more of chloroxylenol (parachlorometaxylenol),
  • acedapsone acetosulfone sodium; alamecin; alexidine; amdinocillin; amdinocillin; pivoxil; amicycline; amifloxacin; amifloxacinmesylate; amikacin; amikacin sulfate; aminosalicylic acid; aminosalicylate sodium; amoxicillin; amphoraycin; ampicillin; ampicillin sodium; apaicillin sodium; apramycin; aspartocin; astromicin sulfate; avilamycin; avoparcin; azithromycin;
  • azloeillin azlocillin sodium
  • bacampicillin hydrochloride bacitracin
  • bacitracin bacitracin
  • cefinetazole sodium cefonicid monosodium; cefonicid sodium.; cefoperazone sodium;
  • ceforariide cefotaxime sodium; cefotetan; cefotetan disodium; cefotiam hydrochloride; cefoxitin; cefoxitin sodium; cefpimizole; eefpimizole sodium; cefpiramide; cefpiramide sodium; cefpirome sulfate; cefpodoxime; proxetil; cefprozil; celroxadine; cefsulodin sodium; ceftazidime;
  • ceftibuten ceftizoxime sodium; ceftriaxone sodium; cefcroxime; cefuroximeaxetil;
  • cefuroximepivoxetil cefuroxime sodium; cephacetrile sodium; cephalexin; cephalexin hydrochloride; cephaloglycin; cephaloridiiie; cephalothin sodium; cephapirin sodium;
  • cephradine cetocycline hydrochloride; cetophenicol; chloramphenicol;
  • cycloserine dalfopristin; dapsone; daptomycin; demeclocycline; demeclocycline hydrochloride; demecycline; denofiiiigin; diaveridine; dicloxacillin; dicloxacillin sodium; dihydrostreptomycin sulfate; dipyrithione; dirithromycin; doxycycline; doxycycline calcium; doxycyclinefosfatex; doxycyclinehyclate; droxacin sodium; enoxacin; epicillin; epitetracycline hydrochloride;
  • erythromycin erythromycin; erythromycin acistrate; erythromycin estolate; erythromycin ethylsuccinate;
  • erythromycin gluceptate erythromycin lactobionate; erythromycin propionate; erythromycin stearate; ethambutol hydrochloride; ethionamide; flerexacin; floxacillin; fludalanine; flumequiiie; fosfomycin; fosfomycintromethamine; fumoxieillin; furazoliuni chloride; furazoliumtartrate;
  • gloximonam gramicidin; haloprogin; hetacillin; hetacillin potassium; hexedine; ibaftoxaein; imipenem; isoconazole; isepamicin; isoniazid; josamycin; kanamycin sulfate; kitasaraycin;
  • levofuraltadone levopropylcillin potassium; lexithromycin; lincomycin; lincomyci
  • hydrochloride lomefloxacin; lomefloxacin hydrochloride; lomefloxacinmesylate; loracarbef; mafenide; meclocycline; meclocyclinesulfosalicylate; megalomicin potassium phosphate; mequidox; meropenem; methacycline; methacycline hydrochloride; methenainine; methenamine hippurate; methenamine mandelate; methicillin sodium; metioprim; metronidazole
  • hydrochloride metronidazole phosphate; mezlocillin; mezlocillin sodium; minocycline;
  • minocycline hydrochloride mirincamycin hydrochloride; monensin; moneosinsodiumr;
  • monovalent silver salts nafcillin sodium; nalidixate sodium; nalidixic acid; natainycin;
  • nebramycin neomycin palmitate; neomycin sulfate; neomycin undecylenate; netilmicin sulfate; neutramycin; nifuiradene; mfuraldezone; nifuratel; nif ratrone; nifurdazil; nifurimide;
  • nifiupirinol nifurquinazol; nifurthiazole; nitroeycline; nitrofurantoin; nitromide; norfloxacin; novobiocin sodium; octenidinedihydrochloride, octenidinediacetate, octcnidinedigluconatc, ofloxacin; onnetoprim; oxacillin and oxacillin sodium; oximonam; oximonam sodium; oxolinic acid; oxytctracycline; oxytetracycline calcium; oxytetracycline hydrochloride; paldimycin; paracMorophenol; paulomycin; pefloxacin; pefloxaciiimesylate; penamecillin; penicillins such as penicillin g benzathine, penicillin g potassium, penicillin g procaine, penicillin g sodium, penicillin v, penicillin v benzathine, pen
  • pentizidonc sodium phenyl aminosalicylate; piperacillin sodium; pirbenicillin sodium;
  • piridicillin sodium piridicillin sodium.
  • pMlmycin hydrochloride pivampicillin hydrochloride
  • rolitetracycline rolitetracycliiie nitrate; rosaramicin; rosaramicin butyrate; rosaramicin propionate; rosaramicin sodium phosphate; rosaramicinstearate; rosoxacin; roxarsone;
  • roxithromycin sancycline; sanfetrinem sodium; sarmoxicillin; sarpiciliin; scopafungin; silver acetate; silver nitrate, nanocrystalline silver, silver polystyrene sulfonate (cross-linked” and non- cross-linked); silver carboxymethyl cellulose, silver polysaccharides (such as silver chondroitin sulfate and the like), silver carbene compounds, sisomicin; sisomiein sulfate; sparfloxacin; spectinomycin hydrochloride; spiramycin; stallimycin hydrochloride; steffimycin; streptomycin sulfate; streptonicozid; sulfabenz; sulfabenzamide; sulfacetamide; sulfacetamide sodium;
  • sulfacytine sulfadiazine; sulfadiazine sodium; sulfadiazine silver; sulfadoxine; sulfalene;
  • sulfamerazine sulfameter; sulfamethazine; sulfamethizole; sulfamethoxazole;
  • sulfamonomethoxine sulfamoxole
  • sulfamlate zinc sulfanitran
  • sulfasalazine sulfasomizole
  • siilfat azole sulfazamet
  • sulfisoxazole sulfisoxazole acetyl
  • sulfisboxazolediolamine siilfat azole; sulfazamet; sulfisoxazole; sulfisoxazole acetyl; sulfisboxazolediolamine;
  • sulfomyxin sulopenem; sultamricillin; suncillin sodium; talampicillin hydrochloride; teicoplanin; temafloxacin hydrochloride; temocillin; tetracycline; tetracycline hydrochloride; tetracycline phosphate complex; tetroxopiim; thiamphenicol; thiphencillin potassium; ticarcillincresyl sodium; ticarcillin disodium; ticarcillin monosodium; ticlatone; tiodonium chloride; tobramycin; tobramycin sulfate; tosufloxacin; trimethoprim; trimethoprim sulfate; trisulfapyrimidines;
  • the anti-inflammatory agent can be one or more of hydrocortisone, hydroxy-triamcinolone, alphamethyldexamethasone, dexamethasone-sodium phosphate, dexamethasone; beclomethasone' dipropionate, clobetasolvalerate, desonide, desoxymethasone, desoxycorticosterone acetate, dexamethasone, dichlorisone, diflorasonediacetate, diftucortolonevalerate, fluadrenolone, fluclaroloneacetonide, fludrocortisone, flu methasonepivalate, fluosinoloneacetonide.
  • fluocinoEide flucortinebutylester, fluocortolone, fluprednidene (fluprednylidene)acetate, flurandrenolone, halcinonide, hydrocortisone acetate, hydrocortisone butyrate,
  • methylprednisolone triamcinoloneacetonide, cortisone, cortodoxone, flucetonide,
  • fludrocortisone difluorosonediacetate, fluradrenaloneacetonide, medrysone, amc, amcinafide, betamethasone and the balance of its esters, chlorprednisone, chlorprednisone acetate, clocortelone, clescinolone, dichlorisone, difluprednate, flucloronide, flunisolide,
  • fluoromethalone fluperolone, fluprednisolone, hydrocortisone valerate, hydrocortisone
  • cyclopentylproprionate hydrocortamate, meprednisone, paramethasone, prednisolone, prednisone, beclomethasonedipropionate, betamethasonedipropionate, triamcinolone
  • prostaglandin 11 synthetase inhibitors (Cox I or Cox II), flurbiprofen, ketorolac, suprofen, nepafenac, amfenac, indoniethacin, naproxen, ibuprofen, bromfenac, ketoprofen, mec!ofenamale, piroxicam, sulindac, mefanamic acid, diflusinal, oxaprozin, tolmetin, fenoprofen, benoxaprofen, nabumetome, etodolac, phenylbutazone, aspirin, oxyphenbutazone, NCX-4016, HCT-1026, NCX-284, NCX-456.
  • the wound dressing may be any suitable shape or size, including a square, rectangle, circle, oval, triangle, strip or any other suitable shape in any desired size.
  • the wound dressing can also be sterilized, if required, prior to packaging or application to a wound.
  • the most preferred sterilization methods are X-ray irradiation and y-irradiation. Both of these sterilisation methods are compatible with the preferred adhesives of the present invention and did not affect the adhesion or release properties of the adhesives.
  • the invention relates to an adhesive skin patch comprising a backing layer and a pressure-sensitive adhesive layer comprising a compound according to Formula (I) on one side of the backing layer.
  • the backing layer preferentially comprises an ether-based urcthanc resin obtained from at least one member selected from the group consisting of polyoxytetramethylene glycol, butanediol, polyethylene glycol, and polypropylene glycol as a diol component, and methylene diphenyl-diisocyanate as an isocyanate component.
  • the weight-average molecular weights of the polyoxytetramethylene glycol, polyethylene glycol, and polypropylene glycol used as the diol component are not particularly limited but are preferably in the range of 500 to 3,000. It is also preferable that,
  • the ether-based uretliane resin contains 5 to 60% by weight of the polyoxytetramethylene glycol and 10 to 50% by weight of the polyethylene glycol. More preferably, the ether-based uretliane resin contains 5 to 45% by weight of the
  • polyoxytetramethylene glycol and 20 to 45% by weight of the polyethylene glycol.
  • a random copolymer of, for example, polyoxytetramethylene glycol and polyethylene glycol as the diol component, ensures high moisture permeability while preventing water swellability.
  • a chain extender may also be used. Conventional chain extenders may be used. Examples thereof include diols such as ethylene glycol, propylene glycol, and butanediol, and diamines such as ethylenenediamine and triethylenediamine.
  • the backing layer for an adhesive skin patch in this embodiment has moisture permeability of a 30 ⁇ -thick layer of preferably 800 g ' n -24 hrs or more and 4,000 g m 2 -24 lirs or less, more preferably 1,000 g/rrf-24 hrs or more and 4,000 g/nt 2 -24 hrs or less, and particularly preferably 1,300 g/ni 2 -24 hrs or more and 4,000 g/m 2 -24 hrs or less.
  • the moisture permeability is obtained by charging a predetermined amount of water in a vessel having a predetermined size of aperture, sealing the opening of the vessel with a layer, allowing the vessel to stand under the conditions of a temperature of 40°C and a relative humidity of 30% RH for 24 hours, and measuring an amount of water decreased per unit nr.
  • the backing layer for an adhesive skin patch in this embodiment in a thickness of 10 ⁇ to 50 ⁇ , has a tensile strength in at least one direction of preferably 5 to 30 N/20 mm-width, an elongation in at least one direction of preferably 400% to 1 ,000%, and a tear strength in at least one direction of preferably 400 to 1 ,000 N/cm-thickness.
  • This design allows the backing layer to achieve flexibility and conforniability to the skin.
  • the backing layer preferably has a tensile strength in at least one direction of 10 to 22 N/20 mm-width, an elongation in at least one direction of more preferably 600% to 900%, and a tear strength in at least one direction of more preferably 550 to 850 N/cm-thickness.
  • the backing layer for an adhesive skin patch, of the present embodiment in a thickness of 10 ⁇ to 50 ⁇ , has a 100% modulus in at least one direction of preferably 1 to 5 N/20 mm-width.
  • the pressure-sensitive adhesive layer that is on one side of the backing layer comprises a compound according to Formula (1). It is preferable that the pressure-sensitive adhesive layer is formed from at least one kind selected from the group consisting of an acrylic pressure-sensitive adhesive consisting mainly of an acrylic acid ester, a silicone pressure-sensitive adhesive consisting mainly of polyorganosiloxane, and a urethane pressure-sensitive adhesive consisting mainly of polyether polyurethane and/or polyester polyurethane.
  • an acrylic pressure-sensitive adhesive for example, an acrylic acid ester-based polymer is mixed with a carboxylic acid ester that is compatible with the acrylic acid ester-based polymer and a crosslinking agent and the resulting mixture is subjected to crosslinking treatment to obtain, the objective pressure-sensitive adhesive layer.
  • the carboxylic acid ester has 16 or more carbon atoms and is liquid or paste at room temperature.
  • the acrylic acid ester-based polymer means a polymer that consists mainly of (meth)acrylic ester and is copolymerized with a monomer copolymerizable therewith as necessary.
  • the (meth)acrylic acid ester include (meth )acrylic acid alkyl esters in which the alkyl group has 2 or more carbon atoms and which has 2 or more and 18 or less carbon atoms. Specific examples thereof include ethyl, propyl, butyl, pentyl, hexyl, octyl, nonyl, decyl, dodeeyl, etc. esters of (meth)acrylic acid. It is preferable that one or more from among these (meth)acrylic acid esters be used.
  • the alkyl ester chains may be either linear or branched.
  • the monomers that are copolymerizable with the (meth)acrylic acid ester include, for example, carboxyl group-containing monomers such as (meth)acrylic acid, itaconic acid, and maleie acid, hydroxyl group-containing monomers such as 2-hydroxyIethyl(meth)acrylate and 2- hydroxypropyl (meth)acrylate, alkoxy group-containing monomers such as
  • methoxypolyethylene glycol (meth)acrylate and ethoxydiethylene glycol (meth)acrylale
  • styrene styrene derivatives
  • vinyl monomers such as vinyl acetate and N-vinyl-2-pyrrolidone, and so on.
  • One or more of these monomers may be used to copolymerize the (meth)acryiic acid esters therewith.
  • the acrylic acid ester-based polymer desirably has a glass transition temperature of 260 or less.
  • the glass transition temperature of the acrylic acid ester-based, polymer at 260K or less, adhesion to the skin can be sufficiently exhibited so ' that the resultant pressure-sensitive adhesive layer is desirable as one for a pressure-sensitive adhesive sheet for medical use or hygine materials.
  • gel-like pressure-sensitive adhesive layer can. be obtained by mixing an acrylic acid ester-based polymer, a carboxylic acid ester, and a crosslinking agent and forming erossl inked moiety in at least a portion thereof.
  • the pressure-sensitive adhesive layer thus obtained can have a decreased elastic modulus in minute deformed regions, so that adhesion (wetting) of the surface of the pressure-sensitive adhesive layer to the unevenness of the surface of skin increases and sufficient adhesion to the surface of skin can be exhibited.
  • stress applied to the surface of skin can be released or dispersed.
  • the carboxylic acid esters that can be preferably used in this embodiment include esters of various fatty acids such as phfhalic acid, maleic acid, adipic acid and stearic acid with alkyl alcohols, esters with polyhydnc alcohols such as ethylene glycol and glycerol, and soon.
  • esters obtained by using monohydric alcohols such as ethyl mynstate.
  • the carboxylic acid esters used herein should have 16 or more carbon atoms. If the carboxylic acid esters have 15 or less carbon atoms, the backing layer tends to absorb liquid, components in large amounts so that swelling deformation of the backing layer occurs.
  • the above-mentioned carboxylic acid esters when the above-mentioned carboxylic acid esters are blended, at least one kind from among them is dissolved in the acrylic acid ester-based polymer.
  • a blending amount of the carboxylic acid is not particularly limited.
  • the carboxylic acid ester in the range of 30 to 100 mass parts be added to 100 mass parts of the acrylic acid ester-based polymer.
  • crosslinked moiety when the acrylic acid ester-based polymer having dissolved therein the above-mentioned carboxylic acid ester is used, it is necessary that crosslinked moiety be formed in at least a portion of the polymer.
  • crosslinking treatment is performed.
  • chemical crossiinkmg treatment may be perfonned by using an organic peroxide compound, an isocyanate compound, an organic metal salt, a metal chelate, an epoxy compound or the like or physical crosslinking treatment may be performed by using ionizing radiation.
  • the resin composition (pressure-sensitive adhesive) that forms the pressure-sensitive adhesive layer may be blended with various additives, e.g., plasticizers such as glycerol and polyethylene glycol, water-soluble or water-absorbing resins such as polyacrylic acid and
  • polyvinylpyrrolidone polyvinylpyrrolidone
  • tackifiers such as rosin-based, lerpene-based, petroleum-based tackifiers
  • various types of softening agents such as fillers, pigments.
  • additives such as fillers, pigments.
  • carboxylic acid esters having unsaturated bonds are used as the carboxylic acid ester, it is feared that the physical properties will change due to oxidation deterioration caused by oxygen in the atmosphere, thus failing to exhibit desired characteristics, so that it is preferable that conventional antioxidants are blended in the resin composition (pressure-sensitive adhesive).
  • the thickness of the pressure-sensitive adhesive layer is set in the range of 10 ⁇ to 100 pm. If the thickness of the pressure-sensitive adhesive layer is less than 10 pm, it may happen that no sufficient adhesion is exhibited during application to the skin or wound. On the other hand, if the thickness of the pressure-sensitive adhesive layer is above 100 ⁇ , it may happen that permeability of water vapor on levels that are required for adhesive skin patches cannot be obtained.
  • the invention in a second preferred embodiment, relates to wound dressing that is a medical, patch in which the backing layer is a laminated film comprising an elastomer film having provided on one side thereof a supporting film, and the substrate layer is an adhesive layer, said adhesive layer being formed on the elastomer film side of the laminated film, wherein the adhesive layer mainly comprises an acrylic polymer and both the adhesive layer and the supporting film comprise a component compatible with the acrylic polymer and that is liquid or paste at ordinary temperature.
  • This embodiment provides a medical patch for application on skin excellent in workability and handleability which exhibits so high an adhesivity that the elastomer film and the supporting film cannot be easily peeled off each other during production (e.g.
  • the supporting film and/or the adhesive layer comprises a liquid or paste component (as determined at 20°C). More preferably, the elastomer film has the liquid or paste component.
  • the elastomer employable herein examples include polyethylene, polyvinyl chloride, ethylene- vinyl acetate copolymer, polyamide, polyester, polyurethane, and acrylic polymer. Particularly preferred among these elastomers are polyamide, polyester, polyurethane and acrylic polymer, which have a high permeability to water vapor, because they cannot impede the perspiration from the skin.
  • the thickness of the elastomer film is preferably predetermined to be from 10 pm to 150 ⁇ , more preferably from 20 pm to 70 pm. When the thickness of the elastomer film falls below 10 ⁇ . it is likely that the resulting film can break during peeling.
  • the modulus of the elastomer film at 50% elongation is preferably predetennined to be from 0.2 to 15 N/mm as measured at ordinary temperature and humidity by a tensile test from the standpoint of flexibility that allows the adhesive sheet to follow the contour of the skin.
  • the supporting film of this embodiment is laminated on the elastomer film to reinforce the flexible elastomer, improving the producibility and handleability of the adhesive sheet.
  • the supporting film is preferably transparent or semi-transparent taking into account visibility that allows the confirmation of sticking site in use. Further, the supporting film normally has a relatively high elastic modulus with respect to the elastomer film.
  • the modulus of the supporting film at 50% elongation is preferably from 2 to 200 N/mm 2 , more preferably from 8 to 50 N/mm 2 as measured at ordinary temperature and humidity by a tensile test.
  • the elastic modulus of the supporting film is properly determined by the elastic modulus of the elastomer film but is normally from about 3 to 20 times that of the elastomer film.
  • the supporting film has been previously subjected to various treatments on the side thereof on which the elastomer film is to be laminated because it is necessary that the elastomer film be laminated properly kept adhesive to the supporting film.
  • these treatments include corona discharge, plasma treatment, and ultraviolet treatment.
  • die material to be used as supporting film examples include polyolefin such as polyethylene and polypropylene, polyester such as polyethylene terephthalate, polyamide such as nylon, polyvinyl chloride, and polyvinylidene chloride.
  • the supporting film may be a composite film containing such a. single film laminated with paper, nonwoven cloth, woven cloth, knitted cloth or metal foil in addition to such a single film.
  • a polyolefin. or polyester film from the standpoint of visibility or cost.
  • any of those mentioned for the first embodiment above can be used.
  • Preferred for this embodiment is an adhesive mainly containing an acrylic polymer having a low irritation against the skin and an excellent transparency, the water vapor permeability of which can be highly predetennined.
  • acrylic polymers include those obtained by the copolymerization of a monomer such as (meth)acrylic acid alkyl ester (e.g., ethyl (meth)acrylate, propyl (meth)acrylate.
  • hydrophilic monomers such as (meth)acrylic acid, itaconic acid, maleic acid, hydroxyethyl (meth)acrylate, mcthoxyethyl (meth)acrylate, etlioxyethyl (meth)acrylate, butoxyethyl (meth)acrylate and ethylene glycol (meth
  • the thickness of the adhesive layer is preferably from 10 ⁇ to 100 ⁇ from the standpoint of adhesiveness to the skin, flexibility that allows the adhesive sheet to follow the contour of the skin and permeability to water vapor.
  • the adhesive layer is preferably subjected to crosslink itig by treatment with a heat-crosslinking agent such as isocyanate compound, organic pero ide, epoxy group-containing compound and metal chelate compound or treatment by ultraviolet rays, gamma-rays, electron, rays or the like to improve the adhesiveness thereof.
  • the liquid or paste component to be incorporated in the adhesive layer plays an important role of adjusting the adhesion between the elastomer film and the supporting film.
  • the liquid or paste component in the adhesive layer partly moves to the supporting film through the elastomer film, attaining substantial equilibrium, with the elapse of about 24 hours at ordinary temperature.
  • This phenomenon causes the adhesion between the elastomer film and the supporting film to be deteriorated, making it possible for the elastomer film and the supporting film., which has been, stuck fast to each other during preparation, to be peelable off each other in use.
  • carboxylic acid ester is preferably used, more preferably glycerin aliphatic acid ester.
  • the content of the liquid or paste component varies with the kind of the adhesive and elastomer film but nonnally is from 20 to 200 parts by weight based on 100 parts by weight of the adhesive or from 5 to 30 g/m as basic weight.
  • the invention in a third preferred embodiment relates to a wound dressing comprising a backing layer and a substrate layer comprising a compound according to Formula (1), wherein the substrate layer is an adhesive layer comprising a rubber-based adhesive, a polymer having a water-absorbing property and/or a water-swelling property, and a metal oxide and/or a metal salt, said polymer having the water-absorbing property and/or the water-swelling property being a polymer containing a functional group having an ability to form a salt and/or to coordinate.
  • compounds according to Formula (1) can be delivered to the wound while at the same time the adhesive layer absorbs exudate from the wound.
  • the polymer having the water-absorbing property and/or the water-swelling property forms ionic or coordinate bonds to metal ions generated from the metal oxide and/or metal salt, and the formation of such ionic or coordinate bonds serves to improve the adhesion of the adhesive composition, to maintain the shape retention property of the adhesive layer, to prevent the adhesive composition from dissolving into body fluid or flowing out, and to enable the adhesive layer to efficiently absorb an exudate and hold the absorbed liquids therein.
  • the backing layer is not particularly limited and can be any of the backing layers mentioned previous for the other embodiments.
  • the backing layer is preferably a film or sheet made of polyolefins, polyesters, polyurethanes, polybutadiene, polyamides, acrylic copolymers, or the like and nonwoven or woven fabrics made of polyesters, acetates, or the like.
  • polyether polyurethanes, polyether-polyamide block polymers, and the like are advantageously used as stretchable materials.
  • use of a porous backing having no open cells is preferred.
  • the backing is in the form of a film having a thickness of about from 10 to 100 ⁇ .
  • the backing has a thickness below 10 ⁇ .
  • the dressing has poor mechanical strength or handling properties, if the thickness of the backing exceeds 100 ⁇ , the dressing shows poor fitness and comfort to the body or has poor handling properties or moisture permeability.
  • a multilayered backing is preferred which comprises a film or sheet of any of the above-described kinds and a nonwoven or woven fabric laminated therewith on the side opposite the side where an adhesive layer is to be formed.
  • the backing has a moisture permeability of from 300 to 5,000 g/m 2 -24hr, preferably from 500 to 2,000 g/m 2 -24hr.
  • Moisture permeabilities as low as below 300 g/nr-24hr are not preferred in that, when the dressing is kept being applied to the body for a long time period, evaporation of the water that has absorbed, by the adhesive layer is diminished due to the low moisture permeability of the backing and, as a. result, the adhesive layer changes in
  • composition and part of the adhesive layer becomes more apt to flo out.
  • moisture permeabilities exceeding 5,000 g/m 2 24hr are not preferred in that the surface of the wounded part to which the dressing has been applied dries excessively due to the high moisture permeability of the backing and, as a. result, cure of the wound is retarded.
  • measured values of moisture permeability are obtained by the Payne cup method.
  • the adhesive layer in the dressing of this embodiment comprises an adhesive composition having the property of water-absorbing and/or the property of water-swelling.
  • This adhesive composition comprises a rubber-based adhesive, a polymer having the water-absorbing property and/or the water-swelling propeity, and a metal oxide and/or a metal salt, and the polymer having the water- absorbing property and/or the water-swelling property contains a functional group having the ability to form a. salt and/or to coordinate.
  • the adhesive layer is formed at a thickness of from. 10 to 4,000 ⁇ . It is preferable that the thickness of the adhesive layer is about from 10 to 1 ,000 ⁇ when the dressing is applied to a wound from which an exudate is oozing out in a relatively small amount, and is about from 1,000 to 4,000 ⁇ when the dressing is applied to a wound from which an exudate is oozing out in a relatively large amount. Small adhesive layer thicknesses are preferred in that the dressing of the preferred embodiment can have transparency and, hence, the wound to which the dressing lias been applied can be examined visually without the necessity of stripping off the dressing.
  • the rubber-based adhesive used in the adhesive layer examples include adhesives containing polyisobutylene, natural rubber, a polyurethane, a styrene-isoprene-styrene teleblock polymer, an acrylic polymer, polyvinyl acetate), an ethylene- vinyl acetate copolymer, or the like as a main component. It is necessary to use a rubber-based adhesive which has elasticity sufficient to fully relax a stress resulting from the water absorption and swelling of the polymer which is present in the adhesive layer along with the rubber-based adhesive and has the water-absorbing property and/or the water-swelling property.
  • the rubber-based adhesive preferably is an adhesive which contains polyisobutylene as the base polymer for the adhesive, particularly an adhesive
  • a high molecular weight polyisobutylene having a viscosity-average molecular weight of from 900,000 to 2,000,000 is added, along with the low molecular weight polyisobutylene described above, in an amount of from 5 to 20% by weight based on the weight of the rubber-based adhesive.
  • the polymer having the water-absorbing property and/or the water-swelling property which is added to the adhesive layer in the dressing of this embodiment, is a polymer containing a functional group having the ability to fonn a salt and/or to coordinate.
  • tMs polymer a polymer which, when immersed in physiological saline, shows high saline penetrability and high saline- absorbing capacity is employed.
  • polystyrene resin examples include gelatin, pectin, carboxymelhyl cellulose (and its sodium salt), algiiiic acid (and its sodium salt), glucomannan, xanthine gum, locust bean gum, carrageenan, methyl vinyl ether- inaleic anhydride copolymers, and acrylic acid- vinyl alcohol copolymers.
  • examples thereof further include so-called highly water-absorbing polymers such as starch-acrylic acid graft polymers, acrylic acid-acrylamide copolymers, and crosslinked carboxymethyl cellulose. These polymers can be used alone or in combination of two or more thereof.
  • a polymer which does not contain a functional group having the ability to form a salt or to coordinate such as karaya gum, guar gum, poly( ethylene glycol), polyacrylaniide, polyvinyl alcohol), a starch-acrylonitrile graft polymer, or crosslinked dextrin, can be used in combination with the polymer containing a functional group having the ability to form a. salt and/or to coordinate.
  • the metal oxide and/or metal salt contained in the adhesive composition is one which, when the adhesive layer of the dressing applied to a wound absorbs an exudate from the wound or body fluids, releases metal ions which form ionic or coordinate bonds to the polymer having the water- absorbing property and or (he water-swelling property,
  • the metal salt consists of a water-soluble metal salt alone, a sparingly-water-soluble metal salt alone, or a combination thereof. Where the water-soluble metal salt is added, the adhesive composition quickly combines by absorption of exudates in the adhesive layer. On the other hand, where the sparingly-water-soluble metal salt is added, the adhesive composition gradually combines to maintain a sustained combined state.
  • water-soluble metal salt or metal oxide is defined that 5 g or more of a metal salt or metal oxide dissolves in 100 g water, while the term “sparingly-water- soluble metal salt or metal oxide” is defined that less than 5 g of a metal salt or metal oxide dissolves in 100 g water.
  • water-soluble metal salt examples include aluminum salts such as alum, burnt alum (anhydrous alum), aluminum sulfate, aluminum lactate, aluminum salicylate, and aluminum nitrate and other metal salts such as calcium chloride, iron chloride, copper sulfate, and barium chloride. These can be added alone or in combination of two or more thereof.
  • Examples of the sparingly- water-soluble metal salt or metal oxide include aluminum hydroxide, aluminum phosphate, aluminum citrate, aluminum benzoate, calcium hydroxide, calcium citrate, calcium carbonate, calcium hydroxide, calcium oxalate, calcium phosphate, calcium tartrate, zinc citrate, calcium oxide, aluminum oxide, zinc oxide, copper oxide, silver oxide, titanium oxide, silver chloride, barium sulfate, and calcium sulfite. These can be used alone or in combination of two or more thereof.
  • both the polymer having the water-absorbing property and/or the water-swelling property and the metal oxide and/or metal salt are added to the adhesive layer in the form, of a powder.
  • an average particle diameter of those powders is from 1 to 1 ,000 ⁇ , preferably from 1 to 300 ⁇ . !f transparency of the dressing is required, an average particle diameter of the powders is 50 pm or less.
  • the proportion of each component added is specified below from the standpoints of the adhesion of the adhesive layer to the body, the rate of water absorption or swelling upon water absorption, die amount of water to be absorbed by the adhesive layer, and. the shape retention property of the adhesive layer.
  • the relative amounts of the rubber-based adhesive (A), the polymer having the water-absorbing property and/or the water- swelling property (B), and the metal, oxide and/or metal salt (C) are such that the proportion of (A)/(B)/(C) is generally 30-80/20-65/0.5-20 by weight, preferably 40-60/30-60/2-10 by weight.
  • the invention relates to an adhesive tape or sheet comprising a backing layer and a substrate comprising a. compound according to Formula (1), wherein the substrate is an adhesive composition comprising a copolymer obtained by copolymerization of a monomer mixture containing an acrylic acid alkyl ester having C4 - CI 2 alkyl group, a
  • (meth)aerylic acid and a methacrylic acid alkyl ester having CI - C4 alkyl group, which mixture is "free of a. multifunctional monomer having two or more unsaturated double bonds in a molecule, wherein the copolymer has a. gel-sol ratio of 35:65 to 55:45 and a weight average molecular weight of the sol portion of 300,000 to 500,000.
  • gel-sol ratio is meant a ratio of the weight of the gel portion, to the weight (weight of the sol portion) obtained by subtracting the weight of the gel portion from the initial weight of the copolymer.
  • the weight of the gel portion is obtained by dissolving a predeteimined amount of the obtained copolymer in toluene, filtering and drying a solvent insoluble component (gel portion), and measuring the weight of this component.
  • the copolymer to be used for the adhesive composition of this embodiment contains a gel portion of a lower level than that defined by the above-mentioned gel-sol ratio, adhesion to the skin is improved, but the cohesiveness decreases, which in turn causes inconvenience such as adhesive residue and the like after peeling of the adhesive tape or sheet
  • the gel portion is contained at a higher level than that defined, by the above-mentioned gel-sol ratio, the problem of adhesive residue is resolved but the adhesive layer has a higher cohesive force, thus increasing the resilience of the adhesive layer to the skin, which in turn causes inconvenience in that an adhesive tape or sheet falls from the skin and the like.
  • the weight average molecular weight of the sol portion When the weight average molecular weight of the sol portion is lower than 300,000, the polymer having a low molecular weight is produced in a greater amount, as a result of which an adhesive composition containing such polymer may unpreferably contaminate the skin. In contrast, when the weight average molecular weight of the sol portion is greater than 500,000, the skin is free of contamination but the adhesive layer has an increased cohesive force, which in turn causes inconvenience in that an adhesive tape or sheet unpreferably falls from the skin and the like.
  • the gel-sol ratio of the above-mentioned copolymer and the weight average molecular weight of the sol portion can be adjusted to fall within the above-mentioned range by controlling the composition (monomer charge ratio) of the acrylic acid alkyl ester, niethacrylic acid alkyl ester and (meth)acrylic acid in the monomer mixture, or by changing the kind and amount of a chain transfer agent, polymerization temperature and the like.
  • the weight average molecular weight of the sol portion can be also controlled by adjusting the dripping speed of an emulsified monomer.
  • the invention in a fifth preffered embodiment, relates to an adhesive tape or sheet comprising a backing layer and a substrate comprising a compound according to Formula (1 ), wherein the substrate is an adhesive composition comprising 1 to 5 parts by weight of the (meth)acrylic acid and 3 to 20 parts by weight of the methacrylic acid alkyl ester, per 100 parts by weight of the acrylic acid alkyl ester.
  • the copolymer to be used for the adhesive composition is adjusted to have a gel fraction of 35 to 55%, and the swelling ratio of the gel portion adjusted to 50 to 90 times.
  • the "gel fraction" is calculated as a proportion (unit: %) of the weight of the gel portion relative to the initial weight of the copolymer (weight of the gel portion. + weight of the sol portion).
  • the weight of the gel portion is obtained by dissolving a predetermined amount of the obtained copolymer in toluene, filtering, drying a solvent insoluble component ⁇ gel portion) and measuring the weight thereof.
  • Gel fraction can be measured by weighing the adhesive (weight Wl), immersing the adhesive in toluene at 20°C for 7 days, extracting the soluble components, filtering insoluble matters through a PTFE membrane (average pore size 0.2 ⁇ , drying and weighing the insoluble matter [weight (W2)] and then, calculating the gel fraction from the following formula;
  • the “swelling ratio of the gel portion” is calculated and expressed in a “swelling ratio” (unit: times) of the weight before drying (solvent + gel portion) to that after drying (gel portion), which is obtained by dissolving a predetermined amount of the obtained copolymer in toluene and filtering and measuring the weight, thereafter drying the gei and measuring the weight.
  • the above-mentioned copolymer to be used for this preferred embodiment shows gel fraction of 35 to 55% and swelling ratio of the gel portion of 50 to 90 times, preferably a gel fraction of 40 to 50% and swelling ratio of the gel portion of 60 to 80 times.
  • the adhesive layer shows an improved skin adhesiveness but lower cohesiveness, which in practice causes inconvenience such as adhesive residue and the like.
  • the adhesive composition shows lower adhesiveness, which may possibly cause inconvenience in that the adhesive tape or sheet falls off from the skin and the like,
  • the gel fraction and the swelling ratio of the gel portion of the copolymer can be adjusted to fall within the above-mentioned ranges by changing the charge amount of monomers to be subjected to copolymerization of an acrylic acid alkyl ester, a methaerylic acid alkyl ester and a (nieth)acrylic acid, or by changing the amount of a chain transfer agent, polymerization temperature and the like.
  • the swelling ratio of the gel portion can be also controlled by adjusting the dripping speed of an emulsified monomer.
  • the adhesive composition of the fourth and fifth preferred embodiments can deliver compounds according to Formula (1) while at the same time exhibit superior balance between an adhesiveness that permits sufficient fixing on the skin and a cohesiveness free of adhesive residue upon peeling. This is particularly useful when, the adliesive tape or sheet is applied to a wound.
  • (meth)acrylic aeid are charged in a. monomer mixture, per 100 parts by weight of the acrylic acid alkyl ester.
  • the obtained copolymer shows a. lower glass transition temperature and improved adhesiveness, but lower cohesiveness to possibly leave an adliesive residue upon peeling in practical use.
  • the methaerylic acid alkyl ester is charged in an amount exceeding 20 parts by weight per 100 parts by weight of the acrylic acid alkyl ester, the obtained copolymer shows an increased glass transition temperature and lower adhesiveness.
  • an adhesive tape or sheet is free of an adhesive residue upon peeling from the skin, shows lower adhesion to the skin and possibly causes an increased pain upon peeling due to stick-slip phenomenon and the like.
  • the amount of the (meth)acrylic acid in a monomer mixture is less than 1 part by weight per 100 parts by weight of the acrylic acid alkyl ester, the obtained copolymer shows insufficient adhesiveness, whereas when it exceeds 5 parts by weight, the copolymer used for an adhesive composition may cause lower adhesiveness to the skin.
  • the chain transfer agent is generally added in an amount of 0.02-0.1 part by weight, preferably 0.04 to 0.07 part by weight, per 100 parts by weight of the monomer mixture.
  • the present invention relates to a wound dressing comprising a backing layer and a substrate layer comprising a compound according to Formula (1), wherein the substrate layer is an adhesive layer, comprising an acrylic copolymer (100 parts by weight) obtained from a monomer mixture comprising a (meth)acrylic acid alkyl ester monomer (40-80 wt%), an alkoxy group-containing ethyienically unsaturated monomer (10-60 wt%) and a carboxy group-containing ethyienically unsaturated monomer (1 -10 wt%), and a carboxylic acid ester (20-120 parts by weight),, which is liquid or paste at 2()°C, wherein the acrylic copolymer has a gel fraction of 30-80 wt%.
  • an adhesive layer comprising an acrylic copolymer (100 parts by weight) obtained from a monomer mixture comprising a (meth)acrylic acid alkyl ester monomer (40-80 wt%), an alkoxy group-containing eth
  • the adhesive composition of tins embodiment is capable of delivering compounds according to Fomiula (1) to a wound surface while at the same time causes less steartiitiess of the skin surface and shows superior skin adhesion even daring perspiration.
  • Gel fraction can be measured as described previously.
  • the substrate constituting the wound dressing of this embodiment is not subject to any particular limitation as long as it. can support the adhesive layer.
  • the use of a moisture permeable substrate is preferable.
  • the material of such substrate includes any of those listed previously.
  • the substrate preferably comprises a urethane polymer ⁇ e.g., polyether polyurethane, polyester polyurethane and the like), amide polymer (e.g., polyether polyamide block copolymer and the like), acrylic polymer (e.g., polyacrylate and the like), polyolefin polymer (e.g., polyethylene, polypropylene, ethylene/vinyl acetate copolymer and the like), polyester polymer (e.g., polyether polyester copolymer and the like), cloth (e.g., nonwoven fabric) and the like.
  • a urethane polymer ⁇ e.g., polyether polyurethane, polyester polyurethane and the like
  • amide polymer e.g., polyether polyamide block copolymer and the like
  • acrylic polymer e.g., polyacrylate and the like
  • polyolefin polymer e.g., polyethylene, polypropylene, ethylene/vinyl acetate cop
  • nonwoven fabric, urethane polymer and amide polymer are preferable, because they are particularly superior in water vapor permeation when prepared into an adhesive tape or sheet for application to skin and free of steaminess, whitening and the like when adhered to the skin surface.
  • the substrate may be a monolayer film made of any one of the above-mentioned materials, or a laminate film consisting of plural films made of a single material or two or more kinds of materials.
  • the above- mentioned substrate has a thickness of 10- 100 ⁇ , preferably 20-40 ⁇ , so that
  • the acrylic copolymer to be used, for the adhesive composition of this embodiment is a copolymer obtained from a monomer mixture of a (mcth)acrylic acid alkyl ester monomer, an alkoxy group-containing ethylenically unsaturated monomer, and a carboxy group-containing ethylenically unsaturated monomer.
  • the (meth)acrylic acid alkyl ester monomer imparts adhesiveness (or skin adhesion property) to an adhesive layer.
  • the adhesive layer made from a (meth)acrylic acid alkyl ester monomer is advantageous in that it causes relatively less irritation to the skin, and adhesion to the skin is not easily degraded by use for a long time.
  • (meth)acrylic acid alkyl ester monomer is exemplified by linear or branched alkyl ester having 2 or more, preferably 6 to 15, carbon atoms. Examples thereof include ethyl ester, propyl ester, butyl ester, pentyl ester, hexyl ester, heptyl ester, octyt ester, nonyl ester, decyl ester and dodecyl ester of acrylic acid or methacrylic acid and the like. These esters may be used alone or in combination of two or more thereof.
  • the amount of the (meth)acrylic acid alkyl ester monomer to be copolynierized is less than 40 wt , the obtained acrylic copolymer does not show sufficient skin adhesion, whereas when it exceeds 80 wt%, the obtained acrylic copolymer shows decreased cohesion, which may result in an adhesive residue after peeling off thereof from the skin surface.
  • the alkoxy group-containing ethylenically unsaturated monomer imparts hydrophilicity to the acrylic copolymer to afford water vapor permeability and hygroscopicity of the adhesive layer.
  • alkoxy group-containing ethylenically unsaturated monomer preferred is alkoxy alkyl acrylate or alkoxy polyethyieneglycol acrylate containing alkoxy having 1 to 4 carbon atoms. Examples thereof include methoxyethyl acrylate, ethoxyethyl acrylate, butoxyethyl acrylate, methoxy polyethyieneglycol.
  • the above-mentioned alkoxy group-containing ethylenically unsaturated monomer is desirably copolynierized and contained in the acrylic copolymer in a proportion of 10-60 wt%, preferably 20-50 wt%.
  • the amount of copotymerization is less than. 10 wt%, sufficient hydrophilicity and skin adhesion necessary for the adhesive layer during perspiration cannot be afforded.
  • it exceeds 60 wt% the adhesive shows poor skin adhesion of an impractical level.
  • carboxy group-containing ethylenically unsaturated monomer its carboxyl group acts as a reaction point in the cross linking treatment, and improves internal cohesion of the adhesive layer.
  • This component is important for the preparation of an adhesive composition for application to skin according to the present embodiement.
  • Typical examples of such monomer include acrylic acid, methacrylic acid, itaconic acid, crolonic acid, fumaric acid, maleic acid (anhydride) and the like. Of these monomers, acrylic acid and methacrylic acid are preferable from the aspects of copolymerization performance, handling property and the like.
  • the above-mentioned carboxy group-containing ethylenically unsaturated monomer is copolynierized and contained in the acrylic copolymer in a proportion of about 1 -10 wt%, preferably 3-8 wt%.
  • the adhesive layer shows improved internal cohesion, but also shows unpreferably stronger irritation to the skin.
  • the acrylic copolymer of this embodiment preferably has a weight-average molecular weight of not more than 1,000,000, preferably 500.000 - 900,000.
  • the adhesive composition may be subjected to a chemical crosslinking treatment to adjust the gel fraction of the acrylic copolymer to a predetermined range.
  • an adhesive composition after a chemical crosslinking treatment is processed to give an adhesive layer and the adhesive layer is subjected to ionization irradiation to adjust the gel fraction, to a predetermined range, thereby adjusting the internal cohesion of the adliesive layer.
  • the adhesive composition before chemical crosslinking treatment preferably has lower internal cohesion, and for this end, the weight-average molecular weight is preferably not more than 1 ,000,000.
  • die adhesive composition before chemical crosslinking treatment has a weight-average molecular weight of an acrylic copolymer of above 1 ,000,000, the internal cohesion of the adhesive layer thus formed may be increased too high to impair adhesion to the skin.
  • the adhesive composition for application to skin contains carboxylic acid ester, which is liquid or paste at room temperature (25°C).
  • carboxylic acid ester which is liquid or paste at room temperature (25°C).
  • the carboxylic acid ester needs to be liquid or paste at room temperature.
  • Carboxylic acid ester which is solid (e.g., wax) at room temperature, is hardly dispersed uniformly in an adhesive composition but shows low compatibility with the composition. Consequently, the adhesive layer may not permit adhesion to the skin or uniform adhesion to the skin, which is unpreferable in this embodiment.
  • the carboxylic acid ester which is liquid or paste at room temperature (20°C), preferably shows affinity for and compatibility with acrylic copolymer, as well as affinity for water produced during perspiration.
  • Specific examples include esters of monoliydric alcohols such as ethyl myristate, isopropyl myristate, isopropyl palmitate, butyl stearate, isopropyl isostearate, hexyl laurate, cetyl lactate, myristyl lactate, diethyl phthalate, octyldodecyl myristate, octyldodecyl oleate, Iiexyldecy!
  • the above-mentioned carboxylic acid ester includes both saturated fatty acid ester and unsaturated fatty acid ester.
  • saturated fatty acid ester is preferable, particularly saturated fatty acid ester having 8 to 10 carbon atoms is more preferable.
  • glycerine ester is preferable in view of small irritation to the skin and the economical aspects.
  • carboxylic acid esters glycerine ester of saturated fatty acid having 8-10 carbon atoms is most preferable.
  • triglyceryl caprylate tri glyceryl caprate and triglyceryl 2- ethylhexanoate.
  • the wound dressing comprises a pressure-sensitive adhesive layer
  • the adhesive comprises a mixture of a radiation-crosslinkable polymer (A) composed of at least 40% by weight of CI to C18 alkyl (meth)acrylates and a polymer (B) composed of at least 20% by weight of vinylpyrrolidone and of less than 40% by weight of C 1 to CI 8 alkyl (meth)acrylates.
  • the fraction of the polymer (B) in the mixture is less than 15% by weight, based on the sum of (A)+(B),
  • the compound according to Formula (1) may be uniformly mixed in this adhesive composition or it may be coated on the surface of the adhesive layer.
  • the wound dressing comprises a pressure-sensitive adhesive layer, wherein the adhesive comprises a radiation-crosslinkabie polymer (C) composed of at least 40% by weight of CI to C 18 alkyl (meth)acrylates and comprising vinylpyrrolidone as
  • the amount of vinylpyrrolidone in the polymer (C) is less than 15% by weight.
  • the compound according to Formula (1 ) may be uniformly mixed in this adhesive composition or it may be coated on the surface of the adhesive layer.
  • the wound dressing comprises a pressure-sensitive adhesive layer, wherein the adhesive comprises a polymer derived from monomes consisting essentially of: (a) from about 50 to 80% by weight of alkyl acrylate or mcthacrylate wherein the alkyl group contains from, about 4 to 12 carbon atoms; (b) from about 20 to 40% by weight of hydroxyalkyl acrylate or mcthacrylate wherein the alkyl group contains from about 2 to 4 carbon atoms; (c) from about 0 to 35% by weight of alkyl acrylate or methacrylate wherein the alkyl group contains from about 1 to 3 carbon atoms; (d) from about 0 to 10% by weight of glycidyl acrylate or mcthacrylate; and (e) from about 0 to 10% by weight of acrylic acid, the dressing laving a water vapor transmission rate of at least 1000 liters vapor/m 2 /24 hours at 40°C and 80% relative humidity difference,
  • the wound dressing comprises a pressure-sensitive adhesive layer, wherein the adhesive comprises a silicone pressure sensitive adhesive comprising (a) a silicone fluid; (b) a silicate resin; and (c) a cohesive strengthening agent selected from the group consisting of nonionic surfactants, fatty acid esters of glycerol and solid particulate materials, said solid particulate materials being selected from the group consisting of metallic salts of fatty acids, metallic salts of phosphoric acid, metallic salts of carbonic acid, polysaccharides, carboxvpolymethylene, polyvinylpyrrolidone, polyvinylalcohol, amorphous precipitated silicas having a surface area of between about 10 and 200 m 2 /g.
  • the adhesive comprises a silicone pressure sensitive adhesive comprising (a) a silicone fluid; (b) a silicate resin; and (c) a cohesive strengthening agent selected from the group consisting of nonionic surfactants, fatty acid esters of glycerol and solid particulate materials, said solid
  • the invention relates to an adhesive tape or sheet comprising a backing layer and a substrate comprising a compound according to Formula (1 ), wherein the substrate is an adhesive composition as described in EP Application No, 13 198 936.0 which is incorporated herein by reference.
  • the Adhesive composition comprises a cross- linked polycondensate (A); and an oil additive (B); wherein the cross-linked polycondensate contains repeating units derived froma dicarboxylic acid (a) and a diol (b); wherein the weight average molecular weight of the polycondensate (A) before cross-linking is from.
  • the dicarboxylic acid (a) is preferably a dicarboxylic acid selected from general formula (I),
  • R l is absent or selected from C 1 - 15 alkylene, C2- 15 alkenylene, and C2- 15 alkynylene, wherein each of these groups is optionally substituted;
  • R2 is selected from CI -12 alkylene, C2-12 alkenylene, and C2- 12 alkynylene, each of which may contain one or two 5-7-membered rings, which may optionally be condensed wherein each of these groups is optionally substituted;
  • R3 is absent or selected from CI -15 alkylene, C2-15 alkenylene, and C2-1 5 alkynylene wherein each of these groups is optionally substituted;
  • each of Ra and Rb is independently selected from hydrogen, alkyl groups having 1 to 24 carbon atoms, and glycerol.
  • the diol (b) is a diol selected from general formula (II),
  • R4 is absent or selected from C I -15 alkylene, C2-15 alkenylene, and C2-15 alkynylene, wherein each of these groups is optionally substituted
  • R5 is selected from CI -12 alkylene, C2-12 alkenylene, and C2-1.2 alkynylene, each of which may contain one or two 5-7-membered rings, which may optionally be condensed, wherein each of these groups is optionally substituted
  • R6 is absent or selected from C 1 - 15 alkylene, C2- 15 alkenylene, and C2- 15 alkynylene, wherein each of these groups is optionally substituted.
  • the above dicarboxylic acid and diol are preferably ditner of fatty acids and dimer of fatty alcohols.
  • oil additive is selected from sorbitan mono- or di-esters of fatty acids, PEG diester, sesame oil, isosorbide diester, mixtures of isosorbide diesters, sorbitol mono- and diesters, oleate esters as well as vernonia oil or mixtures thereof.
  • the oil additive for this embodiment, or indeed any of the preferred emobdiments disclosed herein, may be selected from any natural or synthetic, organic or mineral oil which is suitable for topical application to the human skin.
  • the oil additive may also be selected from the group of softeners, and plasticizers employed in polymer industry, provided the softener or plastieizer is suitable for topical application to the human skin.
  • the oil additive is colorless, and its viscosity is lower than that of the polycondensate. It is also preferred that the polycondensale is fully soluble in the oil additive or in the mixture of the oil additive and an organic solvent.
  • the oil additive can for instance be one or more oils selected from the following list, but it is not limited thereto; sorbitan mono- or di -esters of fatty acids such as sorbitan ester of oleic acid, oleate esters, soybean oil, citrate ester, vernonia oil, PEG (Mw 100-1000) and. PEG derivatives such as PEG ether (such as dimethyl PEG) or PEG esters such as PEG distearate.
  • oils selected from the following list, but it is not limited thereto; sorbitan mono- or di -esters of fatty acids such as sorbitan ester of oleic acid, oleate esters, soybean oil, citrate ester, vernonia oil, PEG (Mw 100-1000) and.
  • PEG derivatives such as PEG ether (such as dimethyl PEG) or PEG esters such as PEG distearate.
  • fatty acids such as myristic acid, palmitic acid, stearic acid, lauric acid, oleic acid, isostearic acid, neodecanoic acid, trimethylhexanoic acid and neoheplanoic acid; the esters of these fatty acids such as isopropyl myristate; fatty alcohols such as myristyl alcohol, cetyl alcohol, oleyl alcohol and lauryl alcohol; aliphatic pyrrolidon.es such as N-lauryl-2-pyrrohdoiie; terpen es such as 1 - menthol, d-limonene and cc-terpineol; alkanes such as heptane, octane, nonane and decane; and substances acting as solubilizers and transdermal absorption promoters of medicinal ingredients such as crotamiton and ⁇ -, ⁇ - and ⁇ -cyclodextrin.
  • fragrant/refreshing materials such as L-menthol, camphor, thymol, mint oil, castor oil, fennel oil, star anise oil, cinnamon oil, oil of cloves, thiamine oil, turpentine oil, eucalyptus oil, lavender oil, lemon oil, orange oil, bergamot oil and rose oil.
  • fatty acid esters of monovalent alcohols such as cetyl octanoate, hexyl laurate, isopropyl myristate, isopropyl palmitate, butyl stearate, myristyl lactate, and the like; dibasic acid esters such as dioctyl adipate, diethyl sebacate, dioctyl sebacate, dioctyl succinate, and the like; fatty acid esters of polyvalent alcohols and the like such as propylene glycol dicaprate, glycerol trioctanoate, glycerol
  • oil additive examples include glycols such, as ethylene glycol, diethylene glycol, propylene glycol, dipropylene glycol, tripropylene glycol, methylene glycol, poly(propy!ene glycol) and the like; fats and oils such as olive oil, castor oil and the like; lanolin; hydrocarbons such as squalane and liquid paraffin; various surfactants; ethoxylated stearyl alcohol; glycerol monoesters such as oleic acid monoglyceride, caprylic acid monoglyceride and lauryl acid monoglyceride; dialkyl ester of polyalkylene glycol such as poly(propylene glycol); glycerol diester such as glycerol diacetate and the like, glycerol triester such as glycerol triacetate and the like, or a mixture thereof; fatty acid alkyl ester such as triethyl citrate and the like; long chain alcohol; higher fatty acid alky
  • the cross-linked polycondensate has a gel content value between 60 % and 95%, preferably between 70 % and 80%
  • the preferred embodiements 1 to 1 1 as described above can be generalised or combined with any of the other preferred features disclosed herein.
  • any of the preferred adhesives may comprise a. compound according to Formula (1) ' uniformly mixed therein or may comprise a compound according to Formula (1) coated on a surface thereof.
  • the wound dressing may be an adhesive patch.
  • adhesive compositions were prepared by mixing a polymer with the desired amount of compound according to Fomiula ( 1 ), plasticizer (optional), tackifier (optional) and solvent (optional). The obtained viscous paste was mixed homogeneously. The mixture was then coated onto a release liner or backing/carrier substrate and cured. Lastly, the sheet was laminated and sterilized.
  • Example 1-1 Preparation of sterile hot-melt UV cured acrylate containing isosorbide
  • An adhesive comprising the acrylate acResin A 260UV (BASF) (10 g) and 0.6 wt% of ground isosorbide was coated on a release liner (SILPHAN S 1R1003; Siliconature) at 50 ⁇ thickness, cured by 350 mJ/cmf of UV-C, laminated by nonwoven substrate (BR6316; Ahlstrom) and sterilized at 25 kGy gamma.
  • Example 1-1 The same procedure as Example 1-1 was followed except that 1.3 wt% of ground isosorbide was used.
  • Example 1-1 The same procedure as Example 1-1 was followed except that 1.9 wt% of ground isosorbide was used.
  • Example 1-2 The same procedure as Example 1-2 was followed except that the wound dressing was not sterilized.
  • An adhesive composition comprising the acrylate Duro-Tak 387-2516 (Henkel) (15 g) and 1.3 wt% of ground isosorbide was coated on release liner (SILPHAN S 1 1003; Siliconature) at 30 ⁇ thickness, cured at 130°C / 5min and laminated by nonwoven substrate (M1573F;
  • An adhesive comprising an acrylic copolymer according to EP 1 184 039 and 1.9 wt% of ground isosorbide was prepared into a 50 ⁇ thick sheet.
  • the sheet was laminated by nonwoven substrate (BR6316; Ahlstrom).
  • An adhesive comprising polyester (10 g), 0.6 wt% of ground isosorbide, 2.5 wt% of
  • DESMODUR N3600 (Bayer) as crossliiiker and 100 wt% of Polysorb ID 37® (Roquette Freres, France) was coated on a release liner (SILPHAN S 1 1003; Silieonature) at 150 ⁇ thickness, cured, at 130 °C for 5 min, and laminated by polyurethane substrate (EU50; Smith & Nephew).
  • the polyester was obtained by polycondensation of a dimer diol with a dimer diacid as follows: 150.15 g of Pripol 1009 and 149.85 g of Pripol 2033 were loaded in a 500 mL reactor equipped with a vacuum adaptor and a mechanical stirring system (using an "anchor" shaped stirrer) and mixed at 150 - 220 rpm. Next 15 mg of Ti(O n Bu)4 was added to the reaction mixture and the colorless viscous solution was heated at 180°C under vacuum (pressure ⁇ 10 mbar) and kept under these conditions for 2h00 after which the heating temperature was set at 225°C for 3h00 (pressure ⁇ 5 mbar). Subsequently the pale yellow reaction mixture was allowed to cool under vacuum; once its temperature reached 130-140°C, the reaction vessel was vented and discharged, Example 7 Preparation of hot-melt UV cured acrylate coated by isosorbide on surface
  • An adhesive comprising the acrylate acResin A 260UV (BASF) was coated on a release liner at 50 pm thickness, cured by 350 mJ/cm 2 of UV-C, laminated by nonwoven substrate (BR6316; AMstrom) and sterilized at 25 kGy gamma. Then, 5% of the adhesive surface was coated with 20 wt% isosorbide solution in isopropanol to a 15 pm target thickness.
  • wound dressings prepared above were subject to a peel test.
  • wound dressing samples were slit to a width of 10mm and length 60mm. Samples were placed on porcine skin. Sample materials were applied on substrate and pressed with a 2kg roller twice, 30 min setting time was allowed before testing. The samples were removed at 180 degrees at a rate of 300 mm/min. The peel force was measured with a load cell units of grams force.
  • wound dressings prepared above were subject to a release test, in this text, wound dressing samples were slit to a width of 25mm and length 25mm. The samples were placed in the middle of the Petri dishes (approximately 60mm diameter) with the adhesive surface as the upper surface After removing the release liner, 7 ml of phosphate-buffered saline solution was added. The samples with PBS solution were shaken gently (70 rpm) and PBS solution was collected at each samplmg time point (4hr, 24hr). The concentration of active component was measured by LCMS (UFLCXR-LCMS2020; Shimadzu) and total release amount was calculated.

Abstract

La présente invention concerne un pansement pour plaies qui comporte : (i) une couche hachurée; (ii) une couche de substrat comportant au moins un composé selon la formule (1) : R1 et R2 pouvant être identiques ou différents et étant choisis dans le groupe constitué d'hydrogène, de -SO3M et d'un groupe chimique physiologiquement hydrolysable, M représentant un cation, de préférence un cation métallique, et le groupe chimique physiologiquement hydrolysable étant choisi dans le groupe constitué d'un groupe alkyle, d'un groupe alkylcarbonyle, d'un groupe alcénylcarbonyle, d'un groupe arylcarbonyle d'un groupe hétéroarylearbonyle, d'un groupe alcoxycarbonyle, d'un groupe aryloxycarbonyle, d'un groupe hétéroaryloxycarbonyle, d'un groupe alkyléther, d'un groupe alcényléther, d'un groupe éther d'aryle et d'un groupe hétéroaryléther. Le groupe ou fragment alkyle est constitué de groupes alkyles non substitués ou substitués, à chaîne droite ou à chaîne ramifiée ou cycliques ayant de 1 à 22 atomes de carbone, le fragment alcényle étant constitué de groupes alcényle non substitués ou substitués, à chaîne droite ou à chaîne ramifiée ou cycliques ayant de 2 à 22 atomes de carbone, le fragment aryle étant constitué de groupes phényle ou phénylalkyle non substitués ou substitués, le fragment alkyle contenant de 1 à 3 atomes de carbone et le fragment phényle étant non substitué ou substitué, et le fragment hétéroaryle étant un noyau hétérocyclique aromatique à 5 ou 6 chaînons contenant un ou deux hétéroatomes choisi dans le groupe constitué de l'azote, de l'oxygène et du soufre.
PCT/EP2016/053463 2015-02-23 2016-02-18 Pansement pour plaies WO2016135038A1 (fr)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021047450A1 (fr) * 2019-09-12 2021-03-18 比亚迪股份有限公司 Batterie, module de batterie, bloc-batterie et automobile

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Publication number Priority date Publication date Assignee Title
US4711904A (en) * 1986-08-04 1987-12-08 Luzzi Louis A Method of treating skin disorders
EP0528191A1 (fr) * 1991-07-22 1993-02-24 Nitto Denko Corporation Pansement
WO1994023713A1 (fr) * 1993-04-22 1994-10-27 Minnesota Mining And Manufacturing Company Composition transdermique anti-inflammatoire
US6106856A (en) * 1994-03-09 2000-08-22 The Board Of Governors For Higher Education, State Of Rhode Island And Providence Plantations Transdermal delivery of calcium channel blockers, such as nifedipine
EP1184039A2 (fr) * 2000-09-01 2002-03-06 Nitto Denko Corporation Composition adhésive pour la peau et bande ou feuille adhésive contenant cette composition
EP1285670A2 (fr) * 2001-08-23 2003-02-26 Nitto Denko Corporation Composition adhésive médicale et ruban ou feuille adhésifs contenant ladite composition
US20050169975A1 (en) * 2004-02-03 2005-08-04 Nitto Denko Corporation Film base material for adhesive skin patch and adhesive skin patch
EP2886578A1 (fr) * 2013-12-20 2015-06-24 Nitto Denko Corporation Adhésif cutané hydrophile

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4711904A (en) * 1986-08-04 1987-12-08 Luzzi Louis A Method of treating skin disorders
EP0528191A1 (fr) * 1991-07-22 1993-02-24 Nitto Denko Corporation Pansement
WO1994023713A1 (fr) * 1993-04-22 1994-10-27 Minnesota Mining And Manufacturing Company Composition transdermique anti-inflammatoire
US6106856A (en) * 1994-03-09 2000-08-22 The Board Of Governors For Higher Education, State Of Rhode Island And Providence Plantations Transdermal delivery of calcium channel blockers, such as nifedipine
EP1184039A2 (fr) * 2000-09-01 2002-03-06 Nitto Denko Corporation Composition adhésive pour la peau et bande ou feuille adhésive contenant cette composition
EP1285670A2 (fr) * 2001-08-23 2003-02-26 Nitto Denko Corporation Composition adhésive médicale et ruban ou feuille adhésifs contenant ladite composition
US20050169975A1 (en) * 2004-02-03 2005-08-04 Nitto Denko Corporation Film base material for adhesive skin patch and adhesive skin patch
EP2886578A1 (fr) * 2013-12-20 2015-06-24 Nitto Denko Corporation Adhésif cutané hydrophile

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021047450A1 (fr) * 2019-09-12 2021-03-18 比亚迪股份有限公司 Batterie, module de batterie, bloc-batterie et automobile

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