WO2003051408A1 - Hydrogel compositions comprising an acryloyl morpholine polymer - Google Patents
Hydrogel compositions comprising an acryloyl morpholine polymer Download PDFInfo
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- WO2003051408A1 WO2003051408A1 PCT/GB2002/005681 GB0205681W WO03051408A1 WO 2003051408 A1 WO2003051408 A1 WO 2003051408A1 GB 0205681 W GB0205681 W GB 0205681W WO 03051408 A1 WO03051408 A1 WO 03051408A1
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- hydrogel composition
- composition according
- hydrogel
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- 0 *C(c1ccc(*)cc1)=C Chemical compound *C(c1ccc(*)cc1)=C 0.000 description 2
- XKSUVRWJZCEYQQ-UHFFFAOYSA-N CC(c1ccccc1)(OC)OC Chemical compound CC(c1ccccc1)(OC)OC XKSUVRWJZCEYQQ-UHFFFAOYSA-N 0.000 description 1
- CTPZCAXSLRBQFH-UHFFFAOYSA-N CC(c1ccccc1)OC#N Chemical compound CC(c1ccccc1)OC#N CTPZCAXSLRBQFH-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F20/00—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and only one being terminated by only one carboxyl radical or a salt, anhydride, ester, amide, imide or nitrile thereof
- C08F20/02—Monocarboxylic acids having less than ten carbon atoms, Derivatives thereof
- C08F20/52—Amides or imides
- C08F20/54—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
- C08F20/58—Amides, e.g. N,N-dimethylacrylamide or N-isopropylacrylamide containing oxygen in addition to the carbonamido oxygen, e.g. N-methylolacrylamide, N-acryloylmorpholine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/425—Porous materials, e.g. foams or sponges
-
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L15/00—Chemical aspects of, or use of materials for, bandages, dressings or absorbent pads
- A61L15/16—Bandages, dressings or absorbent pads for physiological fluids such as urine or blood, e.g. sanitary towels, tampons
- A61L15/42—Use of materials characterised by their function or physical properties
- A61L15/60—Liquid-swellable gel-forming materials, e.g. super-absorbents
-
- 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
- A61L24/00—Surgical adhesives or cements; Adhesives for colostomy devices
- A61L24/001—Use of materials characterised by their function or physical properties
- A61L24/0031—Hydrogels or hydrocolloids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/008—Hydrogels or hydrocolloids
-
- 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
- A61L26/00—Chemical aspects of, or use of materials for, wound dressings or bandages in liquid, gel or powder form
- A61L26/0061—Use of materials characterised by their function or physical properties
- A61L26/0085—Porous materials, e.g. foams or sponges
Definitions
- the present invention relates to hydrogel compositions, and more particularly to hydrogel compositions suitable for use in wound and burn dressings, biomedical electrodes and other applications where skin compatability is required.
- the invention also relates to a process for the manufacture of the novel hydrogel compositions.
- hydrogel and “hydrogel compositions” used herein are not to be considered as limited to gels which contain water, but extend generally to all plasticised gels and gel compositions, including those containing a non-aqueous plasticiser.
- one or more cross-linking agent comprising a multifunctional unsaturated free-radically photo-polymerisable compound
- the photoinitiator (2) is present in the mixture in step (i) in an amount between about 0.002% and about 0.05% by weight of the total mixture
- the cross-linking agent (3) is present in the mixture in step (i) in an amount less than about 0.5% by weight of the total mixture.
- a non-ionic water soluble monomer will comprise at least one of acrylamide or a mono- or di-N- alkylacrylamide or an analogue thereof, the term "analogue" in this context referring to to non-ionic water soluble monomers containing an alkyl or substituted alkyl group linked to a carbon-carbon double bond via an amido or alkylamido (-CO.NH- or -CO.NR-) function.
- Examples of such analogues are stated to include diacetone acrylamide (N-l,l-dimethyl-3-oxobutyl-acrylamide), vinyl lactams, N-alkylated acrylamides, N,N-dialkylated acrylamides, N-vinyl pyrrolidone and acryloyl morpholine.
- the sole monomer present in the polymerisation reaction is sodium 2-acrylamido-2-methylpropane-sulphonate (NaAMPS).
- the present invention is based upon our unexpected finding that the acryloyl mo ⁇ holine, and particularly the compound N-acryloyl mo ⁇ holine (ACMO), which has the formula:
- compositions may be used as the base monomer in the preparation of a wide range of hydrogels, providing considerable technical advantages compared to known compositions.
- a hydrogel composition comprising a plasticised cross-linked hydrophilic polymer of acryloyl mo ⁇ holine and optionally one or more comonomers.
- a process for the preparation of the hydrogel composition of the first aspect of the invention comprising free-radically polymerising a mixture comprising (1) acryloyl mo ⁇ holine and optionally one or more comonomer and (2) one or more cross-linking agent comprising a multifunctional unsaturated free-radically polymerisable compound; the polymerisation being conducted in the presence or absence of a plasticiser, with the proviso that when the polymerisation is conducted in the absence of a plasticiser, a plasticiser is added to the polymer product of the polymerisation.
- the acryloyl mo ⁇ holine may be N-acryloyl mo ⁇ holine, 1 -acryloyl mo ⁇ holine or 2-acryloyl mo ⁇ holine, most particularly N-acryloyl mo ⁇ hiline.
- the pre-polymerisation reaction mixture (pre-gel) preferably includes the monomer(s) at a total monomer level of from about 5% to about 70% by weight of the total pre-polymerisation mixture, more particularly from about 10% to about 60%) by weight, most preferably from about 15% to about 50% by weight.
- the pre-gel may, if desired, contain entrained air bubbles.
- the air bubbles may suitably be introduced into the pre-gel by mecahnical agitation, e.g. stirring, of the pre-gel. Introduction of the air bubbles typically precedes forming the pre-gel into the desired configuration for curing (e.g. before casting when it is intended to form a sheet hydrogel).
- a hydrogel mass having an internal cellular structure e.g. a foam
- the pre-gel for a hydrogel having an internal cellular structure contains a surfactant, e.g. in an amount of up to about 10% by weight, more preferably between about 1 and about 10%) by weight, more typically about 2% by weight.
- one or more different plasticiser and/or more of the same plasticiser may, if desired, be added to the polymer product of the polymerisation.
- the plasticiser may be selected from aqueous and non-aqueous systems. Water or a mixture of water and a water-miscible organic plasticiser may suitably be used as an aqueous plasticiser. When a non-aqueous plasticiser is used, it may suitably be an organic plasticiser. To the extent required by law, the above statements of the present invention shall be taken to exclude subject-matter which is unpatentable in view of the disclosure contained in PCT Patent Application No. WO-01/96422.
- the hydrogel composition of the present invention may include one or more additional ingredients, which may be added to the pre-polymerisation mixture or the the polymerised product, at the choice of the skilled worker.
- additional ingredients are selected from additives known in the art, including, for example, water, organic plasticisers, surfactants, polymers, electrolytes, chloride sources, bioactive compovmds, personal and body care agents, and mixtures thereof.
- the hydrogel composition of the present invention preferably consists essentially of a cross-linked hydrophilic polymer of acryloyl mo ⁇ holine and optionally one or more comonomers, together with water and/or one or more organic plasticiser, and optionally together with one or more additives selected from surfactants, polymers, electrolytes, chloride sources, bioactive compounds, personal and body care agents, and mixtures thereof, with less than about 10%> by weight (suitably less than about 5% by weight) of other additives.
- the hydrogel composition may suitably be present in the form of a sheet having first and second major faces, each of said first and second major faces being in contact with a protective release layer, for example siliconised plastic or paper.
- the hydrogel composition may be present in the form of a sheet having first and second major faces, one of said first and second major faces being in contact with a protective release layer, for example siliconised plastic or paper, and the other of said first and second major faces being in contact with a backing member, suitably a backing member forming part of a wound or bum dressing, a biomedical electrode or another article where a bioadhesive hydrogel layer is to be provided in use between the article and the skin of a wearer.
- the hydrogel composition may be present in the form of a sheet having a woven or non-woven fabric, or a net, embedded therein.
- the hydrogel sheets may typically have a thickness in the range of about 0.2 mm to about 2 mm.
- a release sheet for example a sheet of plastic or coated plastic (e.g. siliconised plastic) or paper or coated paper (e.g. siliconised paper)
- the hydrogel composition may suitably be coated at a surface weight of hydrogel in the range of about 0.5 kg/m to about 2.5 kg/m .
- the process according to the invention may include initially forming a sheet of the pre-gel, and subsequently carrying out the polymerisation step so that the sheet hydrogel is formed in situ by the polymerisation reaction.
- material is not substantially added to or removed from the resultant hydrogel composition, although in some cases some degree of subsequent conditioning and/or modification may be desirable.
- hydrogel composition When the hydrogel composition contains water, it may for some applications be classed as a high water content hydrogel composition, the expression "high water content” referring particularly to hydrogel compositions comprising more than about 40% by weight of water, more particularly above about 50% by weight, and most preferably between about 60% and about 95% by weight.
- the acryloyl mo ⁇ holine monomer is a liquid at room temperature, and is chemically non-ionic.
- the quality of the hydrogel composition is generally good across a wide range of monomer and plasticiser amounts.
- the quality may suffer - with unacceptable brittleness and syneresis of the plasticiser - at high levels of organic plasticiser, for example above about 50% by weight organic plasticiser.
- This problem can, however, be overcome by inco ⁇ oration of a small amount (e.g. up to about 10% by weight, more particularly up to about 5% by weight) of an ionic comonomer in the pre-gel.
- hydrogel compositions based on ACMO can be unusually tolerant of extremes of ambient temperature and atmospheric dryness.
- the hydrogel will maintain its properties to an acceptable extent and for extended periods of time at very much lower or higher temperatures than room temperature (e.g. between about -10°C and about +30°C), and under a substantially bone dry or fully humid atmosphere. This renders the compositions useful in extreme environments, such as arctic and desert conditions.
- the pre-gel is formed as an aqueous composition containing a salt in substantial saturation or supersaturation in the pre- gel.
- This may conveniently be achieved by initially warming a hydrated form of the salt to a temperature at which the salt melts or dissolved in its water of crystallisation, and adding the ingredients of the pre-gel to the liquid thus formed.
- the elevated temperature which may typically be up to around 60°C, may then be maintained or allowed to slowly fall, to maintain or increase the extent of the saturation or the supersaturation, before the pre-gel is cured by the polymerisation reaction.
- the hydrogel composition of the present invention comprises a plasticised three- dimensional matrix of cross-linked polymer molecules, and has sufficient structural integrity to be self-supporting even at very high levels of internal water content, with sufficient flexibility to conform to the surface contours of the human skin.
- the hydrogel composition preferably has sufficient bioadhesion to adhere to the skin under all skin and moisture conditions likely to be encountered during use.
- Our PCT Patent Application No. WO-00/45864 describes a method whereby the skin adhesion performance of the hydrogel can be predicted and thereby tailored to particular applications.
- hydrogel compositions with which the present invention is concerned generally comprise, in addition to the cross-linked polymeric network, an aqueous plasticising medium and, where electrical conductivity is required, at least one electrolyte, whilst the materials and processing methods used are normally chosen to provide a suitable balance of adhesive and electrical properties for the desired application.
- the one or more ionic comonomer if present, will be water soluble and may be selected from: 2-acrylamido-2-methylpropane sulphonic acid or an analogue thereof or one of its salts (e.g. an ammonium or alkali metal salt such as a sodium, potassium or lithium salts); acrylic acid or an analogue thereof or one of its salts (e.g. an alkali metal salt such as a sodium, potassium or lithium salt); and/or a polymerisable sulphonate or a salt thereof (e.g. an alkali metal salt such as a sodium, potassium or lithium salt), more particularly acrylic acid (3-sulphopropyl) ester or an analogue thereof, or a salt thereof.
- analogue in this context refers particularly to substituted derivatives of 2-acrylamido-2-methylpropane sulphonic acid, of acrylic acid or of acrylic acid (3-sulphopropyl) ester.
- a particularly preferred ionic comonomer is a sodium salt of 2-acrylamido-2- methylpropane sulphonic acid, commonly known as NaAMPS, which is available commercially at present from Lubrizol as either a 50% aqueous solution (reference code LZ2405) or a 58% aqueous solution (reference code LZ2405A) and/or acrylic acid (3-sulphopropyl) ester potassium salt, commonly known as SPA or SPAK.
- SPA or SPAK is available commercially in the form of a pure solid from Raschig.
- the one or more non-ionic comonomer may preferably be water soluble and be selected from acrylamide or a mono- or di-N-alkylacrylamide or an analogue thereof.
- analogue in this context refers to non-ionic water soluble monomers containing an alkyl or substituted alkyl group linked to a carbon-carbon double bond via an amido or alkylamido (-CO.NH- or -CO.NR-) function.
- Examples of such analogues include diacetone acrylamide (N-1,1- dimethyl-3-oxobutyl-acrylamide), vinyl lactams, N-alkylated acrylamides, N,N- dialkylated acrylamides and N-vinyl pyrrolidone.
- cross-linking of the hydrophilic polymer in the hydrogel compositions of the present invention is achieved by presence in the pre-gel of one or more cross- linking agent comprising a multifunctional unsaturated fre-radically polymerisable compound.
- Conventional cross-linking agents are suitably used.
- the cross-linking provides the necessary mechanical stability and controls the adhesive properties of the hydrogel.
- the amount of cross-linking agent required will be readily apparent to those skilled in the art such as from about 0.01% to about 0.5%, particularly from about 0.05% to about 0.4%, most particularly from about 0.08% to about 0.3%, by weight of the total polymerisation reaction mixture.
- Typical cross-linkers include tripropylene glycol diacrylate, ethylene glycol dimethacrylate, triacrylate, polyethylene glycol diacrylate (polyethylene glycol (PEG) molecular weight between about 100 and about 4000, for example PEG400 or PEG600), and methylene bis acrylamide.
- PEG polyethylene glycol
- the one or more organic plasticiser when present, may suitably comprise any of the following either alone or in combination: at least one polyhydric alcohol (such as glycerol, polyethylene glycol, or sorbitol), at least one ester derived therefrom, at least one polymeric alcohol (such as polyethylene oxide) and/or at least one mono- or poly-alkylated derivative of a polyhydric or polymeric alcohol (such as alkylated polyethylene glycol).
- Glycerol is the preferred plasticiser.
- An alternative preferred plasticiser is the ester derived from boric acid and glycerol.
- the organic plasticiser may comprise up to about 45% by weight of the hydrogel composition.
- Any compatible surfactant may optionally be used as an additional ingredient of the hydrogel composition.
- Surfactants can lower the surface tension of the mixture before polymerisation and thus aid processing.
- Non-ionic, anionic and cationic surfactants are preferred.
- the surfactant ideally comprises any of the surfactants listed below either alone or in combination with each other and/or with other surfactants.
- the total amount of surfactant, if present, is suitably up to about 10% by weight of the hydrogel composition, preferably from about 0.05% to about 2% by weight, more preferably from about 0.05% to about 1% by weight.
- Suitable non-ionic surfactants include, but are not limited to, those selected from the group consisting of the condensation products of a higher aliphatic alcohol, such as a fatty alcohol, containing about 8 to about 20 carbon atoms, in a straight or branched chain configuration, condensed with about 3 to about 100 moles, preferably about 5 to about 40 moles and most preferably about 5 to about 20 moles of ethylene oxide.
- a higher aliphatic alcohol such as a fatty alcohol, containing about 8 to about 20 carbon atoms, in a straight or branched chain configuration
- Examples of such non-ionic ethoxylated fatty alcohol surfactants are the Tergitol 15-S series from Union Carbide and Brij surfactants from ICI.
- TergitolTM 15-S surfactants include Cn-C ⁇ 5 secondary alcohol polyethyleneglycol ethers.
- BrijTM 58 surfactant is polyoxyethylene(20) cetyl ether
- non-ionic surfactants include, but are not limited to, those selected from the group consisting of the polyethylene oxide condensates of one mole of alkyl phenol containing from about 6 to 12 carbon atoms in a straight or branched chain configuration, with about 3 to about 100 moles of ethylene oxide.
- non- ionic surfactants are the IgepalTM CO and CA series from Rhone-Poulenc.
- IgepalTM CO surfactants include nonylphenoxy poly(ethyleneoxy) ethanols.
- Igepal CA surfactants include octylphenoxy poly(ethyloneoxy) ethanols.
- Another group of usable non-ionic surfactants include, but are not limited to, those selected from the group consisting of block copolymers of ethylene oxide and propylene oxide or butylene oxide. Examples of such non-ionic block copolymer surfactants are the Pluronic and Tetronic series of surfactants from BASF.
- PluronicTM surfactants include ethylene oxide-propylene oxide block copolymers.
- TetronicTM surfactants include ethylene oxide-propylene oxide block copolymers. The balance of hydrophobic and hydrophilic components within the surfactant together with the molecular weight are found to be important. Suitable examples are Pluronic L68 and Tetronic 1907. Particularly suitable examples are Pluronic L64 and Tetronic 1107.
- non-ionic surfactants include, but are not limited to, those selected from the group consisting of sorbitan fatty acid esters, polyoxyethylene sorbitan fatty acid esters and polyoxyethylene stearates.
- fatty acid ester non- ionic surfactants are the SpanTM, TweenTM, and MyrjTM surfactants from ICI.
- SpanTM surfactants include C ⁇ 2 -C ⁇ 8 sorbitan monoesters.
- TweenTM surfactants include poly(ethylene oxide) C ⁇ 2 -C ⁇ 8 sorbitan monoesters.
- MyrjTM surfactants include poly(ethylene oxide) stearates.
- Anionic surfactants normally include a hydrophobic moiety selected from the group consisting of (about C 6 to about C 0 ) alkyl, alkylaryl, and alkenyl groups and an anionic group selected from the group consisting of sulfate, sulfonate, phosphate, polyoxyethylene sulfate, polyoxyethylene sulfonate, polyoxyethylene phosphate and the alkali metal salts, ammonium salts, and tertiary amino salts of such anionic groups.
- Anionic surfactants which can be used in the present invention include, but are not limited to. those selected from the group consisting of (about C 6 to about C 20 ) alkyl or alkylaryl sulfates or sulfonates such as sodium lauryl sulfate (commercially available as PolystepTM B-3 from Srepan Co.) and sodium dodecyl benzene sulfonate, (commercially available as SiponateTM DS-10 from Rhone-Poulenc); polyoxyethylene (about C 6 to about C 20 ) alkyl or alkylphenol ether sulfates with the ethylene oxide repeating unit in the surfactant below about 30 units, preferably below about 20 units, most preferably below about 15 units, such as PolystepTM B- 1 commercially available from Stepan Co.
- alkyl or alkylaryl sulfates or sulfonates such as sodium lauryl sulfate (commercially available as PolystepTM B-3 from Srepan Co.)
- AlipalTM EP110 and 115 from Rhone-Poulenc (about C 6 to about C 20 ) alkyl or alkylphenoxy poly (ethyleneoxy)ethyl mono-esters and di-esters of phosphoric acid and its salts, with the ethylene oxide repeating unit in the surfactant below about 30 units, preferably below about 20 units, most preferably below about 15 units, such as GafacTM RE- 510 and GafacTM RE-610 from GAF.
- Cationic surfactants useful in the present invention include, but are not limited to, those selected from the group consisting of quaternary ammonium salts in which at least one higher molecular weight group and two or three lower molecular weight groups are linked to a common nitrogen atom to produce a cation, and wherein the electrically-balancing anion is selected from the group consisting of a halide (bromide, chloride, etc.), acetate, nitrite, and lower alkosulfate (methosulfate etc.).
- a halide bromide, chloride, etc.
- acetate acetate
- nitrite nitrite
- lower alkosulfate methosulfate etc.
- the higher molecular weight substituent(s) on the nitrogen is/are often (a) higher alkyl group(s), containing about 10 to about 20 carbon atoms, and the lower molecular weight substituents may be lower alkyl of about 1 to about 4 carbon atoms, such as methyl or ethyl, which may be substituted, as with hydroxy, in some instances.
- One or more of the substituents may include an aryl moiety or may be replaced by an aryl, such as benzyl or phenyl.
- the surfactant comprises at least one propylene oxide/ethylene oxide block copolymer, for example such as that supplied by BASF Pic under the trade name Pluronic P65 or L64.
- Additional polymer(s), typically rheology modifying polymer(s), may be inco ⁇ orated into the polymerisation reaction mixture at levels typically up to about 10% by weight of total polymerisation reaction mixture, e.g. from about 0.2% to about 10%) by weight.
- Such polymer(s) may include polyacrylamide, poly-NaAMPS, polyethylene glycol (PEG), polyvinylpyrrolidone (PVP) or carboxymethyl cellulose.
- a particularly preferred application is in the field of biomedical skin electrodes.
- chloride ions are required to be present in order for the electrode to function.
- Potassium chloride and sodium chloride are commonly used.
- any compound capable of donating chloride ions to the system may be used, for example, lithium chloride, calcium chloride, magnesium chloride or ammonium chloride.
- the amount that should be added is dependent on the electrical properties required and is typically about 0.5-8%) by weight.
- an electrolyte e.g. a salt such as a chloride as mentioned above or another salt such as a nitrate, for example calcium nitrate
- an electrolyte e.g. a salt such as a chloride as mentioned above or another salt such as a nitrate, for example calcium nitrate
- a salt such as a chloride as mentioned above or another salt such as a nitrate, for example calcium nitrate
- compositions prepared according to the present invention are used in biomedical electrodes in generally conventional manner, as will be readily understood by those skilled in this art.
- Additional functional ingredients may also inco ⁇ orated in the reaction mixture used in the invention, including bioactive compounds such as antimicrobial agents
- dermatologically active compounds e.g. citric acid, stannous chloride
- enzymes e.g. citric acid, stannous chloride
- compounds providing a heating or cooling sensation to a patient's body e.g., stannous chloride
- dermatologically active compounds e.g., stannous chloride
- pharmaceutically active agents e.g., the latter being designed to be delivered either passively (e.g. transdermally) or actively (e.g. iontophoretically) through the skin.
- compositions may optionally contain topical, transdermal or iontophoretic agents and excipients.
- the compositions may contain penetration-enhancing agents to assist the delivery of water or active agents into the skin.
- penetration-enhancing agents for use in such applications include methyl oleic acid, isopropyl myristate, Azone®, Transcutol® and N-methyl pyrrolidone.
- Any suitable free-radical polymerisation reaction may be used, according to the monomers present in the pre-gel.
- the range of reactions and their appropriate initiation and other conditions will be well known to those of ordinary skill in this art.
- the free-radical polymerisation may be initiated in generally known manner by light (photoinitiation), particularly ultraviolet light (UV photoinitiation); heat (thermal initiation); electron beam (e-beam initiation); ionising radiation, particularly gamma radiation (gamma initiation); non-ionising radiation, particularly microwave radiation (microwave initiation); or any combination thereof.
- the pre-gel mixture may include appropriate substances (initiators), at appropriate levels, e.g. up to about 5% by weight, more particularly between about 0.002% and about 2% by weight, for example between about 0.05%> and about 2% by weight, which serve to assist the polymerisation and its initiation, in generally known manner.
- the process of tile invention involves free-radical polymerisation and the use of a photoinitiator or a combination of photo- and other initiation.
- the reaction mixture comprises an amount of photoinitiator of from about 0.003% to about 0.5%, and particularly from about 0.003% to about 0.4%, most particularly from about 0.009% to about 0.2%, by weight of the total polymerisation reaction mixture.
- the low levels of photoinitiator described in PCT Patent Application No. WO-01/96422 may be used.
- Preferred photoinitiators include any of the following either alone or in combination: Type I- ⁇ -hydroxy-ketones and benzilidimethyl-ketals e.g. Irgacure 651.
- Photoinitiators of this type that are preferred are those that do not carry substituents in the para position of the aromatic ring. Examples include Irgacure 184 and Daracur 1173 as marketed by Ciba Chemicals, as well as combinations thereof.
- Ri can be any of the following:- hydrogen, H 3 C-S-
- Ri is most preferably hydrogen.
- R 2 can suitably be any of the following:-
- R is most preferably as follows:
- a particularly preferred photoinitiator is 1-hydroxycyclohexyl phenyl ketone; for example, as marketed under the trade name Irgacure 184 by Ciba Speciality Chemicals. Also preferred are Daracur 1173 (2-hydroxy-2-propyl phenyl ketone) and mixtures of Irgacure 184 and Daracur 1173.
- the ingredients will be mixed to provide a reaction mixture in the form of an initial pre-gel formulation, which is most preferably a liquid, and this is then converted into a hydrogel by a free-radical polymerisation reaction.
- air bubbles may be introduced into the pre-gel prior to the polymerisation reaction, for example by mechanical agitation of the pre-gel, where it is desired to produce a hydrogel mass having an internal cellular structure.
- Photo-polymerisation is particularly suitable, and may be achieved using photoinitiators, optionally together with other initiators, such as heat and/or ionizing radiation.
- Photoinitiation will usually be applied by subjecting the pre- gel reaction mixture containing an appropriate photoinitiation agent to ultraviolet (UV) light after it has been spread or coated as a layer on siliconised release paper or other solid substrate.
- UV ultraviolet
- the incident UV intensity, at a wavelength in the range from 240 to 420nm, is typically greater than about 10mW/cm 2 .
- the processing will generally be carried out in a controlled manner involving a precise predetermined sequence of mixing and thermal treatment or history.
- the UV irradiation time scale should ideally be less than 60 seconds, and preferably less than 10 seconds to form a gel with better than 95% conversion of the monomers.
- the extent of irradiation will be dependent on a number of factors, including the UV intensity, the type of UN source used, the photoinitiator quantum yield, the amount of monomer present, the nature of the monomer(s) present, the presence of dissolved oxygen, the presence of polymerisation inhibitor, the thickness of the reaction mixture when coated onto the substrate and the nature of substrate onto which the reaction mixture is coated.
- compositions described herein may suitably be used in a range of skin contact or covering applications where the composition is brought into contact either with skin or with an intermediary article which interfaces between the composition and the skin.
- the composition may be unsupported or may be supported on a backing structure.
- the compositions may suitably be in the form of sheets, coatings, membranes, composites or laminates.
- Such applications include patches, tapes, bandages, devices and dressings of general utility or for specific uses, including without limitation biomedical, skin care, personal and body care, palliative and veterinary uses such as, for example, skin electrodes; wound and burn healing; wound and burn management; skin cooling; skin moisturising; skin warming; aroma release or delivery; decongestant release or delivery; pharmaceutical and drug release or delivery; perfume release or delivery; fragrance release or delivery; scent release or delivery; adhesive use, e.g. in skin contacting devices, ostomy and related incontinence devices, and the like.
- the hydrogel compositions prepared according to the present invention are used in these applications in generally conventional manner, as will be readily understood by those skilled in this art.
- ACMO acryloyl mo ⁇ holine
- acrylic acid (“AA”) comonomer was also added with the ACMO.
- acrylic acid (“AA”) comonomer was also added with the ACMO.
- 2-acrylamido-2-methylpropane sulphonic acid sodium salt (NaAMPS) was also added with the ACMO (see discussion below).
- NaAMPS 2-acrylamido-2-methylpropane sulphonic acid sodium salt
- a salt was also added, if necessary with gentle warming.
- the salt was selected from calcium chloride hexahydrate Examples 23 to 28), calcium nitrate tetrahydrate (Examples 29 and 30), a 50:50 weight mixture of calcium chloride hexahydrate and calcium nitrate tetrahydrate (Example 31), sodium chloride (Example 32) and magnesium chloride hexahydrate (Examples 33 and 34).
- the amounts of the AA and the salt are indicated in the table below.
- the appropriate weight of glycerol was added (Examples 5 to 15, 18 to 22, 27 and 28 only) and the mixture stirred for about 30 minutes.
- Amounts of these initial ingredients for Examples 1 to 22 are shown in parts by weight (normally out of 100, but out of 104 in the case of Example 9); amounts for Examples 23 to 34 are shown in grams.
- a mixture of crosslinker (“XL”) and photoinitiator (“PI”) was made by adding the appropriate weight of IRR280 (PEG400 diacrylate, UCB Chemicals) ("280") to the appropriate weight of photoinitiator, Daracur 1173 (Ciba Specialty Chemicals) ("1173"). The appropriate amount of this liquid mixture was added to the mixture, which was stirred for 1 hour, covered to exclude light.
- the figures for Examples 1 to 9, 12 and 16 to 20 in the table below show the percentage by weight of the initial mixture, at which the PI/XL mixture (6 parts by weight PI: 20 parts by weight XL) is added.
- the figures for Examples 10, 21 and 22 in the table below show the percentage by weight of the initial mixture, at which the PI/XL mixture (10 parts by weight PI: 20 parts by weight XL) is added.
- the figure for Example 11 in the table below shows the percentage by weight of the initial mixture, at which the PI/XL mixture (100.7 parts by weight PI: 108 parts by weight XL) is added.
- Example 13 in the table below shows the percentage by weight of the initial mixture, at which the PI/XL mixture (1 parts by weight PI: 3 parts by weight XL) is added.
- the figure for Example 14 in the table below shows the percentage by weight of the initial mixture, at which the PI/XL mixture (9 parts by weight PI: 10 parts by weight XL) is added.
- the figure for Example 15 in the table below shows the percentage by weight of the initial mixture, at which the PI/XL mixture (35 parts by weight PI: 54 parts by weight XL) is added.
- the figures for Examples 23 to 34 in the table below show the weight of the PI/XL mixture (1 parts by weight PI: 10 parts by weight XL) added.
- the mixture was mechanically agitated with a high speed stirrer, to entrain air bubbles in the pre-gel.
- 50g of the mixture at a coat weight of 1.5kg/sq.m was cured in the laboratory on a tray lined with siliconised paper by passing at a speed of 7m/minute three times under ultra-violet (UN) radiation of 80W/cm from a medium pressure mercury vapour lamp.
- UN ultra-violet
- Example 1 gave a gel which was clear and colourless, soft and leggy.
- Example 2 gave a gel which was clear and colourless, a nice soft gel.
- Example 3 gave a gel which was clear, colourless and tough.
- Example 4 gave a gel which was clear and colourless, a tough and brittle gel.
- Example 5 gave a gel which was clear and colourless, tough and slightly tacky.
- Examples 6 and 7 gave gels which were clear and colourless, tough and tacky. All the above gels were acceptable.
- Example 8 gave a gel which was white, hard and brittle and showed syneresis of the glycerol. This gel was unacceptable for use as a bioadhesive. It is believed that this unacceptability may be more generally observed at very high levels of organic plasticiser. However, as shown by Example 9, the problem is su ⁇ risingly and effectively overcome by the presence of a small amount of the ionic comonomer (NaAMPS) in the pre-gel.
- Example 9 gave an
- Example 10 gave a gel which was clear and colourless, soft and tacky. Examples 11 and 12 gave gels which were leggy. Example 13 gave a gel which was clear and colourless, tough, tacky and brittle. Examples 14 and 15 gave clear leggy gels.
- Example 15 gave a gel which was soft, clear and leggy.
- Example 17 gave a gel which was clear but brittle.
- Example 18 gave a gel which was clear and strong.
- Example 19 gave a gel which was clear but soft.
- Examples 20 to 22 gave gels which were clear and slightly tacky.
- Examples 23 to 34 gave acceptable gels, many of which displayed substantial robustness under extremes of temperature and atmospheric dryness. In summary, all of Examples 10 to 34 produced acceptable gels.
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Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP02804955A EP1458424A1 (en) | 2001-12-19 | 2002-12-13 | Hydrogel compositions comprising an acryloyl morpholine polymer |
JP2003552340A JP2005511862A (en) | 2001-12-19 | 2002-12-13 | Hydrogel composition containing acryloylmorpholine polymer |
AU2002356295A AU2002356295A1 (en) | 2001-12-19 | 2002-12-13 | Hydrogel compositions comprising an acryloyl morpholine polymer |
CA002468988A CA2468988A1 (en) | 2001-12-19 | 2002-12-13 | Hydrogel compositions comprising an acryloyl morpholine polymer |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB0130369.2 | 2001-12-19 | ||
GB0130369A GB0130369D0 (en) | 2001-12-19 | 2001-12-19 | Hydrogel compositions |
GB0205702A GB0205702D0 (en) | 2002-03-11 | 2002-03-11 | Hydrogel compositions |
GB0205702.4 | 2002-03-11 |
Publications (1)
Publication Number | Publication Date |
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WO2003051408A1 true WO2003051408A1 (en) | 2003-06-26 |
Family
ID=26246887
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/GB2002/005681 WO2003051408A1 (en) | 2001-12-19 | 2002-12-13 | Hydrogel compositions comprising an acryloyl morpholine polymer |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP1458424A1 (en) |
JP (1) | JP2005511862A (en) |
AU (1) | AU2002356295A1 (en) |
CA (1) | CA2468988A1 (en) |
WO (1) | WO2003051408A1 (en) |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004028255A1 (en) * | 2002-09-25 | 2004-04-08 | First Water Limited | Antimicrobial compositions |
WO2005068518A1 (en) * | 2003-12-18 | 2005-07-28 | Kimberly-Clark Worldwide, Inc. | Electrically conductive adhesive hydrogels with two initiators |
US7045559B2 (en) | 2003-12-18 | 2006-05-16 | Kimberly-Clark Worldwide, Inc. | Electrically conductive adhesive hydrogels with solubilizer |
EP2163193A1 (en) * | 2008-09-11 | 2010-03-17 | Tyco Healthcare Group LP | Conductive compositions and method |
US7816412B2 (en) | 2007-02-23 | 2010-10-19 | Conmed Corporation | Electrically conductive hydrogels |
DE102011082042A1 (en) | 2011-09-02 | 2013-03-07 | Beiersdorf Ag | Composition, useful as hair cleaning composition, comprises a cationic terpolymer based on acryloylmorpholine compound with a specified range of charge density |
WO2014130567A1 (en) | 2013-02-20 | 2014-08-28 | Carefusion 2200, Inc. | Antimicrobial hydrogel polymers |
CN111905138A (en) * | 2019-05-10 | 2020-11-10 | 陕西佰傲再生医学有限公司 | Hydrogel dressing and preparation method thereof |
CN116284566A (en) * | 2022-09-09 | 2023-06-23 | 南方科技大学 | Photo-curing slurry and organic hydrogel for high-elasticity wearable strain sensor and preparation method thereof |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP6278731B2 (en) * | 2014-02-24 | 2018-02-14 | テルモ株式会社 | Antithrombotic medical material and medical device using the medical material |
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GB1323809A (en) * | 1970-10-20 | 1973-07-18 | Ceskoslovenska Akademie Ved | Method for producing articles from hydrophilic polymers |
US5717049A (en) * | 1996-03-25 | 1998-02-10 | Pharmacia Iovision, Inc. | High refractive index hydrogels prepared from polymers and copolymers of N-benzyl-N-methylacrylamide |
WO2000045864A1 (en) * | 1999-02-02 | 2000-08-10 | First Water Limited | Bioadhesive compositions |
WO2001096422A1 (en) * | 2000-06-15 | 2001-12-20 | First Water Limited | Process for the manufacture of hydrogel compositions and hydrogel compositions manufactured thereby |
-
2002
- 2002-12-13 WO PCT/GB2002/005681 patent/WO2003051408A1/en not_active Application Discontinuation
- 2002-12-13 EP EP02804955A patent/EP1458424A1/en not_active Withdrawn
- 2002-12-13 AU AU2002356295A patent/AU2002356295A1/en not_active Abandoned
- 2002-12-13 CA CA002468988A patent/CA2468988A1/en not_active Abandoned
- 2002-12-13 JP JP2003552340A patent/JP2005511862A/en active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
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GB1323809A (en) * | 1970-10-20 | 1973-07-18 | Ceskoslovenska Akademie Ved | Method for producing articles from hydrophilic polymers |
US5717049A (en) * | 1996-03-25 | 1998-02-10 | Pharmacia Iovision, Inc. | High refractive index hydrogels prepared from polymers and copolymers of N-benzyl-N-methylacrylamide |
WO2000045864A1 (en) * | 1999-02-02 | 2000-08-10 | First Water Limited | Bioadhesive compositions |
WO2001096422A1 (en) * | 2000-06-15 | 2001-12-20 | First Water Limited | Process for the manufacture of hydrogel compositions and hydrogel compositions manufactured thereby |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2004028255A1 (en) * | 2002-09-25 | 2004-04-08 | First Water Limited | Antimicrobial compositions |
WO2005068518A1 (en) * | 2003-12-18 | 2005-07-28 | Kimberly-Clark Worldwide, Inc. | Electrically conductive adhesive hydrogels with two initiators |
US7045559B2 (en) | 2003-12-18 | 2006-05-16 | Kimberly-Clark Worldwide, Inc. | Electrically conductive adhesive hydrogels with solubilizer |
US7816412B2 (en) | 2007-02-23 | 2010-10-19 | Conmed Corporation | Electrically conductive hydrogels |
US8419982B2 (en) | 2008-09-11 | 2013-04-16 | Covidien Lp | Conductive compositions and method |
EP2163193A1 (en) * | 2008-09-11 | 2010-03-17 | Tyco Healthcare Group LP | Conductive compositions and method |
DE102011082042A1 (en) | 2011-09-02 | 2013-03-07 | Beiersdorf Ag | Composition, useful as hair cleaning composition, comprises a cationic terpolymer based on acryloylmorpholine compound with a specified range of charge density |
WO2014130567A1 (en) | 2013-02-20 | 2014-08-28 | Carefusion 2200, Inc. | Antimicrobial hydrogel polymers |
CN105163768A (en) * | 2013-02-20 | 2015-12-16 | 开尔弗森2200有限公司 | Antimicrobial hydrogel polymers |
EP2958600A4 (en) * | 2013-02-20 | 2016-09-21 | Carefusion 2200 Inc | Antimicrobial hydrogel polymers |
CN105163768B (en) * | 2013-02-20 | 2018-04-13 | 开尔弗森2200有限公司 | Antimicrobial aquogel polymer |
CN111905138A (en) * | 2019-05-10 | 2020-11-10 | 陕西佰傲再生医学有限公司 | Hydrogel dressing and preparation method thereof |
CN116284566A (en) * | 2022-09-09 | 2023-06-23 | 南方科技大学 | Photo-curing slurry and organic hydrogel for high-elasticity wearable strain sensor and preparation method thereof |
Also Published As
Publication number | Publication date |
---|---|
EP1458424A1 (en) | 2004-09-22 |
JP2005511862A (en) | 2005-04-28 |
AU2002356295A1 (en) | 2003-06-30 |
CA2468988A1 (en) | 2003-06-26 |
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