[go: up one dir, main page]

WO2012150890A1 - Composition antibactérienne - Google Patents

Composition antibactérienne Download PDF

Info

Publication number
WO2012150890A1
WO2012150890A1 PCT/SE2012/000056 SE2012000056W WO2012150890A1 WO 2012150890 A1 WO2012150890 A1 WO 2012150890A1 SE 2012000056 W SE2012000056 W SE 2012000056W WO 2012150890 A1 WO2012150890 A1 WO 2012150890A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
silver
lipid
silicone oil
aliphatic alcohol
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/SE2012/000056
Other languages
English (en)
Inventor
Anders Carlsson
Bengt Herslöf
Jan HOLMBÄCK
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Lipidor AB
Original Assignee
Lipidor AB
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
Application filed by Lipidor AB filed Critical Lipidor AB
Publication of WO2012150890A1 publication Critical patent/WO2012150890A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/005—Antimicrobial preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/38—Silver; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • A61K38/08—Peptides having 5 to 11 amino acids
    • A61K38/085—Angiotensins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • A61K38/1729—Cationic antimicrobial peptides, e.g. defensins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/22—Hormones
    • A61K38/29—Parathyroid hormone, i.e. parathormone; Parathyroid hormone-related peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/46—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing sulfur
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/55—Phosphorus compounds
    • A61K8/553—Phospholipids, e.g. lecithin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
    • A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
    • A61K8/89—Polysiloxanes
    • A61K8/891—Polysiloxanes saturated, e.g. dimethicone, phenyl trimethicone, C24-C28 methicone or stearyl dimethicone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/02—Local antiseptics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/41—Particular ingredients further characterized by their size
    • A61K2800/413—Nanosized, i.e. having sizes below 100 nm
    • 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
    • A61K9/7007—Drug-containing films, membranes or sheets

Definitions

  • the present invention relates to an antibacterial composition capable of forming a layer comprising a pharmacologically effective amount of an antibacterial agent, to a method of manufacture of the composition and to a method of applying it on a wound.
  • Antibacterial compositions for topical administration are known in the art. Their administration to the skin or to a wound, in particular to skin of which the integrity has been jeopardized by, for instance, inflammation or irritation, is however still problematic.
  • the physical form of silver incorporation ranges from elemental metallic silver nanoparticles to salts of varying sparing solubility in water. In all instances, however, it is the silver ion species, produced by oxidation or dissolution that is believed to be the antimicrobially active agent (Texter J et al., Bactericidal silver ion delivery into hydrophobic coatings with surfactants. J Ind Microbiol Biotechnol [2007) 34: 571-575].
  • composition is easily applicable to the skin or the wound so as to form a coherent layer on it.
  • Still another object of the invention is to provide such a composition that does not cause swelling when applied to the skin.
  • a further object of the invention is to provide such a composition that does not give a burning feeling when applied to the skin.
  • compositions of the aforementioned kind comprising or substantially consisting of an oily lipid, in particular a polar oily lipid, a volatile silicone oil, a silver source, and optionally a lower aliphatic alcohol.
  • the silver source is present in dissolved and/or suspended form in the composition.
  • the silver source comprises silver in elemental and/or ionic form capable of exerting an antimicrobial effect. It is preferably selected from the group consisting of silver salt, in particular salt of monovalent silver (Ag + X ), silver complex, in particular organic silver complex, colloidal silver, silver particles, in particular silver
  • nanoparticles and their mixtures.
  • the silver source is an inorganic silver salt such as silver nitrate or an organic silver salt such as silver dihydrogen citrate.
  • the silver source is monovalent silver ion stabilized by ⁇ -complex formation with a ⁇ -bond of cis- configuration comprised by an unsaturated chain of an oily lipid, such as a mono- or polyunsaturated aliphatic chain, in particular a mono- or polyunsaturated aliphatic chain of a polar oily lipid such as dioleoylphosphatidylcholine (DOPC) and
  • DOPC dioleoylphosphatidylcholine
  • dioleoylphosphatidylethanolamine DOPE
  • examples of other polar lipids useful in the invention include monooleoylglycerol and soy bean lecithin.
  • the silver source is a complex between silver ion and a thiol group-containing compound.
  • Complexes of this kind are disclosed in EP 727 427 Al, which is incorporated herein by reference.
  • the silver source is a complex between silver ion and a N-heterocyclic carbene.
  • Complexes of this kind are disclosed in US 2008/0267867 Al, which is incorporated herein by reference.
  • the silver source is a monovalent silver salt of an anionic surfactant or detergent such as l,4-bis(2- ethylhexyl) sulphosuccinate (dioctyl sulfosuccinate or docusate ⁇ .
  • an anionic surfactant or detergent such as l,4-bis(2- ethylhexyl) sulphosuccinate (dioctyl sulfosuccinate or docusate ⁇ .
  • the silver source is finely dispersed elemental silver, such as of an average particle size of less than 20 ⁇ , in particular of less than 5 ⁇ , and silver nanoparticles, such as of a size of 100 nanometers or less.
  • the composition of the invention consists of a single phase.
  • the low viscosity of the composition allows administration of the composition to the skin or a wound by spraying.
  • the composition forms a coherent layer from which the solvent evaporates or, in respect of the alcohol, if present, may be partially absorbed by the skin or tissue. Evaporation of the volatile components transforms the initially formed layer into a residual layer of oily lipid, in particular of oily polar lipid, and silver source.
  • the composition can comprise other antimicrobial agents, such as antimicrobial peptides or peptides promoting wound healing.
  • Preferred wound healing promoting peptides of the invention include angiotensin II, a wound healing fragment, analog or derivative of angiotensin II, human parathyroid hormone, a wound healing fragment, analog or derivative of human parathyroid hormone, cathelicidin polypeptide LL37, a wound healing fragment, analog or derivative of cathelicidin polypeptide LL37.
  • a wound of which the healing can be promoted by the composition of the invention may, for instance, be a shallow or deep wound formed by incision or other damage of the skin such as by abrasion or a wound caused by burning, such as skin damaged by burning, but also a bone fracture.
  • the present invention is based on the finding that a particular class of solvents, volatile silicone oils, optionally in combination with a lower aliphatic alcohol, are particularly useful in formulating a composition comprising a polar lipid, suitable for incorporation of the antimicrobial agent of the invention.
  • a particular class of solvents, volatile silicone oils, optionally in combination with a lower aliphatic alcohol are particularly useful in formulating a composition comprising a polar lipid, suitable for incorporation of the antimicrobial agent of the invention.
  • the composition of the invention forms an instable polar lipid layer from which the volatile silicone oil and, if present, the lower aliphatic alcohol, evaporate readily, leaving a stable oily polar lipid layer substantially consisting of polar lipid comprising the silver source of the invention.
  • the low viscosity of the composition of the invention seems, i.a., to be due to the inability of polar lipids to form lyotropic liquid crystals, such as lamellar hexagonal and various cubic phases of high viscosity.
  • the composition of the invention is clear and of low viscosity even at concentrations of polar lipid as high as 20 % by weight.
  • polar lipid compositions corresponding to those of the invention but in which the silicone oil component is substituted by a corresponding weighed amount of water are slightly viscous dispersions at low membrane lipid concentrations or thick gels at 20 % by weight of membrane lipid in respect of the composition, the highest membrane lipid concentration tested;
  • the high viscosity of the composition comprising 20 % by weight of membrane lipid does not allow it to be administered by spraying.
  • Silicone oils of pharmaceutical grade useful in the invention are known in the art.
  • useful silicone oils include dekamethylcyclopentasiloxane [Dow Corning ® 345 Fluid and cyclomethicone 5-NF) and dodekamethylcyclohexasiloxane [Dow Corning ® 246 Fluid). While pentasiloxanes and hexasiloxanes are preferred, terra-, hepta-, and octasiloxanes are also potentially useful.
  • the silicone oils of the invention can be used in pure form or in admixture.
  • one or more methyl groups of a siloxane can be substituted by lower alkyl, in particular by ethyl, propyl or isopropyl.
  • Siloxanes partially or fully substituted by lower trifluoroalkyl, in particular trifluoromethyl and pentafluoroethyl, are also useful in the invention.
  • silicone oil in the invention is determined by its volatility.
  • a silicone oil of the invention evaporates easily. This is due to the low heat of vaporization of this class of compounds.
  • a silicone oil having a heat of vaporization (kj/kg) at 25 °C of from about 100 kj/kg to about 300 kj/kg, more preferred of from about 120 kj/kg to about 200 kj/kg are particularly useful. Even more preferred is a silicone oil having a heat of vaporization of from 140 kj/kg to about 180 kj/kg at 25 °C.
  • the silicone oil of the invention provides the composition of the invention with at least the following advantageous features: i] the ability to incorporate high contents of polar lipid material; / ' ) the formation of thermodynamically stable solutions; Hi] the low viscosity of the solutions formed making them suitable for, e.g., spraying, dropping, painting or instilling.
  • the lower aliphatic alcohol of the invention is a C 2 to C 4 alcohol or a mixture of such alcohols, in particular an alcohol selected from C 2 to C3 alcohol and tert- butanol. Particularly preferred is ethanol. Also useful in the invention is a partially or fully fluorinated Ci to C 4 alcohol, a mixture of such alcohols, and a mixture of Ci to C 4 alcohol and a partially or fully fluorinated Ci to C 4 alcohol.
  • the C 2 to C 4 alcohol may comprise 1,2-propanediol, and/or glycerol, in an amount of up to 20 % or 50 % by weight of the C 2 to C 4 alcohol.
  • the oily polar lipid of the invention can be described as a lipid capable of interaction with water (as defined in D. Small, The Physical Chemistry of Lipids. Plenum Press 1986, section 4.3), for example formed of membrane lipid, that is, lipid
  • Membrane lipids contain a polar, hydrophilic head group and one or more lipophilic hydrocarbon chains. This combination makes the membrane lipid molecules amphipathic and enables their association with water and with oil. Membrane lipids can be classified according to their chemical structure, which is a function of how the polar head group is linked to the lipophilic chains. Sphingolipids (linked by sphingosine) and glycerolipids [linked by glycerol) are the two main groups. Depending on the characteristics of the polar head group sphingolipids and glycerolipids can be further classified as phospholipids comprising a phosphate ester head group and glycolipids comprising a carbohydrate head group.
  • membrane lipids are sometimes called, for instance, galactolipids, which are glycerolipids with galactose in the polar head group.
  • galactolipids which are glycerolipids with galactose in the polar head group.
  • Examples of common membrane lipids are phosphatidylcholine (PC),
  • Membrane lipids of interest can be extracted from, for example, egg yolk (egg lecithin), milk and dairy products, soybeans (soy lecithin), other oil crops, oat kernels, and other cereal and grains. These extracts can be further treated to obtain, for instance, PC from soy beans and galactolipids from oats.
  • Preferred polar lipids are galactolipids, in particular galactolipids from oat kernels, or phospholipids from soybeans (soy lecithin or soy-PC).
  • Synthetic or semi-synthetic polar lipids and membrane lipid analogues based on a carbohydrate or phosphate ester moiety are also comprised by membrane lipids of the invention.
  • Examples of synthetic polar lipids comprise dioleoylphosphatidylcholine and dioleoylphosphatidylethanolamine.
  • Other lipids capable of interaction with water are monoglycerides, for example monooleylglycerol.
  • the oily lipid of the invention can be a polar or non-polar lipid, comprising a side chain with a ⁇ -bond of cis-configuration.
  • the oily lipid of the invention comprises an unsaturated mono-, di-, or triglyceride, in particular one comprising one or more mono-unsaturated acyl residues of cis-configuration, most particularly oleic acid.
  • the oily lipid of the invention can be obtained from natural sources or be of synthetic or semi-synthetic origin.
  • the use of a lower aliphatic alcohol such as ethanol for the dissolution of the oily polar lipid of the invention is particularly useful with a lipid with a low chain- melting temperature.
  • the chain-melting temperature is the temperature at which the acyl chains of the membrane lipid undergo a phase transition in an excess of water, from a solid-like state to a melted or liquid-like state.
  • Lipoid S75, Lipoid S45, Phospholipon 50, Lipoid SlOO, and DOPC all have chain-melting temperatures below 0°C and can thus be readily dissolved in absolute ethanol at concentrations up to 50 % by weight and even higher.
  • the polar lipid in particular a membrane lipid mixture such as lecithin or fractionated oat oil, may alternatively be dissolved in a lower aliphatic alcohol and then diluted with a volatile silicone oil, resulting in a low-viscous, sprayable, homogenous liquid.
  • Fractionated oat oil is obtained from crude oat oil and is enriched in polar lipids.
  • non-polar lipids such as triacylglycerols and diacylglycerols
  • polar lipids such as phospholipids and glycolipids.
  • the content of digalactosyldiacylglycerol in fractionated oat oil is about 20 % by weight.
  • Suitable fractionated oat oils are disclosed, for instance, in WO 99/44585 Al.
  • Lipids like phosphatidylethanolamine and dioleylphosphatidylethanol- amine can also be used as the polar lipid component of the invention as such or in admixture with other polar lipids.
  • DOPE has a chain-melting temperature of -16°C in water and can be dissolved in absolute ethanol at 50 % by weight or higher at elevated temperatures (>60°C). Such solution can be diluted with volatile silicone oil such as DC 345, resulting in a clear, low-viscous liquid.
  • the antimicrobial composition of the invention is preferably substantially water-free, in particular has a water content of less than 5 % by weight, preferably of less than 2 % or 1 % by weight and even less than 0.5 % by weight or 0.2 % by weight.
  • the antimicrobial composition of the invention comprises from 10 % by weight to 30 % by weight of membrane lipid, from 10 % by weight to 30 % by weight of ethanol, from 0.01 % by weight to 5 % by weight of antimicrobial agent, the remainder being volatile silicone oil, with the proviso that the content of volatile silicone oil is 40 % by weight or more.
  • Silver l,4-bis(2-ethylhexyl) sulphosuccinate was prepared according to the following procedure which is a modification of the method used by Petit et al., J Phys Chem 1993, 97, 12974-12983.
  • a slurry of 6.7 g of Dowex Monosphere M-31 strongly acidic cation exchange resin in ca 20 ml of deionized water is applied to a 25 x 150 mm glass column. The resin is regenerated by elution with 10 ml of 1.0 M HCl and washed with 10 ml of deionized water followed by 10 ml of methanol/water 1:2 (v/v).
  • 1,4-bis (2 -ethylhexyl) sulphosuccinate [222 mg) is dissolved in 3.0 ml of methanol/water 1:2 (v/v) and applied to the column. 1,4-Bis(2- ethylhexyl) sulphosuccinic acid is eluted by 7 ml of methanol/water 1:2 (v/v).
  • a slurry of 13,5 g of Lewatit CNP 105 weakly acidic cation exchange resin in about 20 ml of deionized water is applied to a second 25 x 150 mm glass column and washed with 10 ml of deionized water, followed by 10 ml of methanol/water 1:2 (v/v).
  • Silver nitrate (164 mg) is dissolved in 5 ml of methanol/water 1:2 (v/v) and applied to the second column.
  • the resin is washed by 5 ml of deionized water followed by 10 ml of methanol/water 1:2 (v/v).
  • the solution of l,4-bis(2-ethylhexyl) sulphosuccinic acid was applied to the second column, and silver 1,4-bis (2 -ethylhexyl) sulphosuccinate is eluted by 23 ml of methanol/water 1:2 (v/v).
  • the eluate is evaporated, resulting in 83.3 mg of a white semisolid residue.
  • compositions according to the invention comprising silver 1,4-bis (2 -ethylhexyl) sulphosuccinate were prepared by mixing a alcoholic solution of docusate silver with volatile silicone oil (DC 245, DC 246 or DC 345) and polar oily lipid by ultrasonication.
  • DC 245, DC 246 or DC 3405 volatile silicone oil
  • polar oily lipid by ultrasonication.
  • composition of the invention comprising Ag + / olefin complex.
  • Silver nitrate (13.7 mg) was dissolved in 4.73 g of ethanol.
  • the silver nitrate solution (1.50 g) was then mixed with DC 345, resulting in a clear homogenous solution.
  • DOPE (48.8 mg) was dissolved in the mixture by ultrasonication.
  • the thus obtained mixture contains 0.07 % by weight of silver nitrate, 2.4 % by weight of DOPE, 24.3 % by weight of ethanol and 73.2 % by weight of DC 345.
  • the concentration of silver nitrate in the non-volatile part of the composition is 2.8 % by weight.
  • the presence of Ag + /olefin complex was demonstrated by 13 C NMR spectroscopy (Table 2).
  • a solution suitable for NMR analysis was prepared in the following manner. Silver nitrate (1.08 mg) and 15.7 mg of DOPE was dissolved in 90.0 mg of methanol-d 4 in a vial by ultrasonic agitation to form a first mixture. In another vial 131.8 mg of chloroform-di was mixed with 516.1 mg of DC 345 to form a second mixture. The first and second mixtures were combined and ultrasonicated. The resulting clear colourless solution was transferred to a 0.5 mm ID NMR tube.
  • composition A Composition B
  • a pre-weighed amount of silver nitrate was dissolved in ethanol.
  • To the solution was added 50 % (w/w) of phospholipid.
  • Complete dissolution of the phospholipid in the ethanolic solution was accomplished by short ultrasonication in a bath-type sonicator at about 40 °C.
  • the resulting clear yellow solutions were diluted with silicone oil and stored in air-tight glass vials at room temperature.
  • Silver nanoparticles prepared by the method of R Das et al., Preparation of Silver Nanoparticles and Their Characterization. AZojon, Journal of Nanotechnology Online, DOI: 10.2240/azojono0129
  • a pre-weighed amount of silver oleate was dissolved in ethanol, then phospholipid was added to the ethanolic solution. After treatment in a bath-type sonicator at about 35°C, a clear solution was obtained. The solution was diluted with the volatile silicone oil and the resulting clear, colourless solution was stored in an airtight glass vial at room temperature.
  • Table 3 Presented in Table 3 are data on miscibility of ethanolic phospholipid solutions with either volatile silicone oil or water. The mixtures with a low content of
  • PL/ethanol in the silicone oil had a clear appearance immediately after preparation, but separated within a month at room temperature.
  • the formulation with a concentration of PL/ethanol of 20 % was miscible with the volatile silicone oil, did not change in appearance during this time period and can thus be considered to be physically stable.
  • the phospholipid of Table 3 is Lipoid S75 manufactured by Lipoid GmbH,
  • This phospholipid material from soybean contains about 68 -
  • PC phosphatidylcholine
  • suitable phospholipid materials are, for example, Lipoid S45, Phospholipon 50, and Lipoid S100, all made from soybean and manufactured by Lipoid GmbH, covering a range of PC content of about 50 % up to 100 %.
  • Further useful phospholipids are synthetic dimyristoylphosphatidylcholine (DMPC), dioleylphosphatidylcholine (DOPC) and dipalmitoylphosphatidylcholine (DPPC).

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Birds (AREA)
  • Medicinal Chemistry (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Endocrinology (AREA)
  • Inorganic Chemistry (AREA)
  • Zoology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biophysics (AREA)
  • Oncology (AREA)
  • Dermatology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Communicable Diseases (AREA)
  • Molecular Biology (AREA)
  • Vascular Medicine (AREA)
  • Marine Sciences & Fisheries (AREA)
  • Emergency Medicine (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une composition antibactérienne formant une couche lipidique qui comprend une huile de silicone volatile, un lipide gras, une source d'argent, et facultativement un alcool aliphatique en C2-C4. La source d'argent est choisie dans le groupe constitué d'un sel d'argent (Ag+X-), d'argent colloïdal, d'un complexe d'argent, de particules d'argent, de nanoparticules d'argent, et de leurs mélanges. La présente invention concerne en outre un procédé de formation de la couche lipidique sur la peau ou sur une plaie, et un procédé de fabrication de la composition. Les ingrédients préférés comprennent les siloxanes, notamment le décaméthylcyclopentasiloxane et le dodécaméthylcyclohexasiloxane, avec un point d'ébullition défini, et un lipide gras polaire, par exemple, un lipide membranaire tel qu'un phospholipide, un glycolipide ou un sphingolipide.
PCT/SE2012/000056 2011-05-02 2012-04-20 Composition antibactérienne Ceased WO2012150890A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SE1100341 2011-05-02
SE1100341-5 2011-05-02

Publications (1)

Publication Number Publication Date
WO2012150890A1 true WO2012150890A1 (fr) 2012-11-08

Family

ID=47107946

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/SE2012/000056 Ceased WO2012150890A1 (fr) 2011-05-02 2012-04-20 Composition antibactérienne

Country Status (1)

Country Link
WO (1) WO2012150890A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014178789A1 (fr) * 2013-05-03 2014-11-06 Lipidor Ab Composition topique et véhicule pour l'administration de principes actifs pharmaceutiques ou cosmétiques
WO2015072910A1 (fr) * 2013-11-14 2015-05-21 Lipidor Ab Compositions topiques pharmaceutiques, cosmétiques et désinfectantes comprenant de la phosphatidylcholine
WO2015120316A1 (fr) * 2014-02-07 2015-08-13 Trevena, Inc. Formes cristallines et amorphes d'un effecteur bêta-arrestine
CN106109351A (zh) * 2016-08-23 2016-11-16 广州洁康卫生用品有限公司 一种杀菌修护清洗剂、制备方法及其应用
US9534017B2 (en) 2008-12-29 2017-01-03 Trevena, Inc. Beta-arrestin effectors and compositions and methods of use thereof
US9611293B2 (en) 2014-05-19 2017-04-04 Trevena, Inc. Synthesis of beta-arrestin effectors
US10278395B2 (en) 2013-03-11 2019-05-07 North Carolina State University Functionalized environmentally benign nanoparticles

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5738859A (en) * 1997-01-17 1998-04-14 Abbe Cosmetic Group International, Inc. Cosmetic composition
EP1066825A1 (fr) * 1999-06-17 2001-01-10 The Procter & Gamble Company Produit antimicrobien pour les soins du corps
US20030170194A1 (en) * 2000-05-19 2003-09-11 Ralf Piotrowiak Pharmaceutical and/or cosmetic composition containing an organosiloxane and a phospholipid
US20040234474A1 (en) * 2001-07-24 2004-11-25 Alvin Berlat Topical pharmaceutical formulation
WO2005023213A1 (fr) * 2003-08-29 2005-03-17 Bio-Gate Ag Produit de soin corporel contenant des particules poreuses d'argent
US20060211820A1 (en) * 2005-03-18 2006-09-21 Jonn Jerry Y Liquid coating compositions
US20060246149A1 (en) * 2003-04-18 2006-11-02 Herwig Buchholz Antimicrobial pigments
US20070149448A1 (en) * 2001-01-29 2007-06-28 Mona Stahle-Backdahl Use of the cathelicidin ll-37 and dervicaties thereof for would healing
KR20090099456A (ko) * 2008-03-17 2009-09-22 (주)에이씨티 은 코팅층 함유 실리카 나노분말, 그의 제조방법 및 이를 포함하는 화장료용 조성물

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5738859A (en) * 1997-01-17 1998-04-14 Abbe Cosmetic Group International, Inc. Cosmetic composition
EP1066825A1 (fr) * 1999-06-17 2001-01-10 The Procter & Gamble Company Produit antimicrobien pour les soins du corps
US20030170194A1 (en) * 2000-05-19 2003-09-11 Ralf Piotrowiak Pharmaceutical and/or cosmetic composition containing an organosiloxane and a phospholipid
US20070149448A1 (en) * 2001-01-29 2007-06-28 Mona Stahle-Backdahl Use of the cathelicidin ll-37 and dervicaties thereof for would healing
US20040234474A1 (en) * 2001-07-24 2004-11-25 Alvin Berlat Topical pharmaceutical formulation
US20060246149A1 (en) * 2003-04-18 2006-11-02 Herwig Buchholz Antimicrobial pigments
WO2005023213A1 (fr) * 2003-08-29 2005-03-17 Bio-Gate Ag Produit de soin corporel contenant des particules poreuses d'argent
US20060211820A1 (en) * 2005-03-18 2006-09-21 Jonn Jerry Y Liquid coating compositions
KR20090099456A (ko) * 2008-03-17 2009-09-22 (주)에이씨티 은 코팅층 함유 실리카 나노분말, 그의 제조방법 및 이를 포함하는 화장료용 조성물

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9534017B2 (en) 2008-12-29 2017-01-03 Trevena, Inc. Beta-arrestin effectors and compositions and methods of use thereof
US10278395B2 (en) 2013-03-11 2019-05-07 North Carolina State University Functionalized environmentally benign nanoparticles
WO2014178789A1 (fr) * 2013-05-03 2014-11-06 Lipidor Ab Composition topique et véhicule pour l'administration de principes actifs pharmaceutiques ou cosmétiques
CN105682686A (zh) * 2013-05-03 2016-06-15 立普妥公司 用于给药的运载体和局部组合物
WO2015072910A1 (fr) * 2013-11-14 2015-05-21 Lipidor Ab Compositions topiques pharmaceutiques, cosmétiques et désinfectantes comprenant de la phosphatidylcholine
WO2015120316A1 (fr) * 2014-02-07 2015-08-13 Trevena, Inc. Formes cristallines et amorphes d'un effecteur bêta-arrestine
US20150225461A1 (en) * 2014-02-07 2015-08-13 Trevena, Inc. Crystalline and amorphous forms of a beta-arrestin effector
US9518086B2 (en) 2014-02-07 2016-12-13 Trevena, Inc. Crystalline and amorphous forms of a β-arrestin effector
US9611293B2 (en) 2014-05-19 2017-04-04 Trevena, Inc. Synthesis of beta-arrestin effectors
CN106109351A (zh) * 2016-08-23 2016-11-16 广州洁康卫生用品有限公司 一种杀菌修护清洗剂、制备方法及其应用

Similar Documents

Publication Publication Date Title
WO2012150890A1 (fr) Composition antibactérienne
KR101748224B1 (ko) 살아있는 유기체의 표면으로 투여하기 위한 지질층 형성 조성물
KR20120129864A (ko) 소포성 제형
WO2021192861A1 (fr) Liquide ionique, solvant, préparation et agent pouvant être absorbé par voie transdermique
EP2709665A1 (fr) Traitement du psoriasis
JP2023522146A (ja) ホスファチジルコリンを含むヒマワリリン脂質組成物
WO2023286120A1 (fr) Agent d'absorption percutanée
EP1909800B1 (fr) Acylglycerophospholipides pour traiter des troubles associes au cancer
DE112013002492T5 (de) Vesikuläre Formulierungen, Verwendungen und Verfahren
DE112013002488T5 (de) Vesikuläre Formulierungen, Kits und Verwendungen
JP7406057B2 (ja) 外用微粒子カプセル製剤及び皮膚外用剤
US20100016269A1 (en) Composition of plant sterol and phosphatidylcholine and method for producing the same
JP2008088133A (ja) ベシクル組成物、及びそれを用いた皮膚外用剤
EP2120873B1 (fr) Forme posologique topique comprenant des composés de glycérol trisubstitué
DE112012001382T5 (de) Arzneimittelfreie Zusammensetzungen und Methoden zur Verminderung von peripheren Entzündungen und Schmerzen
WO2009074239A1 (fr) Mousses pharmaceutiques
JP2023135125A (ja) ベシクル組成物
WO2003020318A1 (fr) Composition d'emulsion eau dans l'huile pour application locale
JPH01307438A (ja) 安全でかつ高度な界面活性を有する脂質組成物
WO2019230964A1 (fr) Composition d'émulsion de type huile dans eau conditionnée
JPH04108732A (ja) Ｐａｆ拮抗剤含有脂肪乳剤

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 12779789

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 12779789

Country of ref document: EP

Kind code of ref document: A1